U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH SPEC IAL RESEARCH RESOURCE ANNUAL REPORT Grant Number RR 0031-04 ACME August 1, 1969 to July 31, 1970 Joshua Lederberg, Ph.D., Principal Investigator Stanford University School of Medicine U. S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE NATIONAL INSTITUTES OF HEALTH SPECIAL RESEARCH RESOURCE ANNUAL REPORT Report Period; From; August 1, 1969 (same as current ]2-month Grant No. budget period) To: July 31, 1970 RR 00311-04 Resource Title Advanced Computer for MEdical Research (ACME) Resource Address Stanford University School of Medicine Palo Alto, California Resource Tel, No, (415) 321-1200 Ext. 6121 Principal Investigator Lederberg, Joshua Title Professor Academic Dept. Genetics Grantee Institution Stanford University School of Medicine type of Institution Private University investigator's Tel. No, (415) 321-1200 Ext. 5801 Name of Institution's Special Research Resource Advisory Committee: ACME Policy Committee Membership of Special Research Resource Advisor (Indicate Chairman) Vv Committee Name Title Department Institution see next page Typed Name and Title of Principal Investigator Signature Date Joshua Lederberg, Professor Typed Name and Title of Grantee Institution Signature Date Official ACME POLICY COMMITTEE MEMBERSHIP May, 19/0 Name Paul Armer Malcolm Bagshaw, Robert Baldwin, J. Weldon Bellville Walter Bodmer, Byron William Brown, Jr., Howard Cann, Edward Feigenbaum, Robert Glaser, M.D. Avram Goldstein Donald Harrison L. Lee Hundley Ronald Jamtgaard Courtney Jones Burt Kopell, Joshua Lederberg, Ph.D. Ellictt Levinthal Lawrence Schneiderman, Bruce Stocker, Howard Sussman, Jobst Von der Groeben Gio Wiederhold Management: Director M.D, Ph.D. MD, Ph.D. Ph.D. M.D. Ph.D. Dean M.D, M.D, Assistant Director Director Deputy Director M.D, Principal Investigator Ph.D. M.D, M.D, M.D, M.D, Consultant to Director Department Stanford Computation Center Radiology Biochemistry Anesthesia Genetics Community and Preven- tive Medicine Pediatrics Computer Science De- partment School of Medicine Pharmacology Cardiology ACME Computer Facility ACME Computer Facility Stanford University Hospital Psychiatry Genetics Genetics Medicine-Ambulatory Medicine-Microbiclogy Pathology Anesthesia ACME Computer Facility Robert Langle, Computation Center Business Manager Institution Stanford University Medical Center Medical Center Medical Center Medical Center Medical Center Medical Center Stanford University Medical Center Medical Center Medical Center Stanford University Stanford University Medical Center Medical Center Medical Center Medical Center Medical Center Medical Center Medical Center Medical Center Stanford University William Yundt, Computation Center Associate Director for Business and Finance Reviewed report Stanford University Advanced Computer for Medical TABLE OF CONTENTS Special Research Resource Annual Report Section I: Resource Identification Section II: Resource Operations A. Description of Resource Operations and Progress B. Summary of Resource Usage C. Resource of Equipment List D. Summary of Publications Section III: Resource Finances A. Summary of Resource Expenditures B. Expenditure Details ~- Direct Costs C. Summary of Resource Funding D. Budget Explanation - Justification section IV: Detailed Description of Resource Projects Grant No. RR 311-04 18 36 HT 48 ug 52 53 29 Grant No. RR 311-04 Section II-A General Description of Resource Operation Introduction: In its fourth year of existence, the ACME Project offered the time-sharing and real-time data-acquisition services developed during the first three years and sought to improve its level of service and reliability. The most significant change during the past year has been the full implementa- tion of “user fees." The fee for service concept was started in March, 1969, but only recently have nearly all users become "eligible" for accepting charges due to grant restrictions imposed by the National Institutes of Health. A brief summary of the years events follows: July, 1969, was a record month for terminal hours yielding 4,400 hours of terminal connect time. In August, N.I.H. awarded a new grant covering ACME. During the fall of 1969, utilization dropped markedly as the full impact of user charges became evident. Many new contract and grant awards from Federal agencies provided fewer dollars than had been hoped for and anticipated. January, 1970, marked the installation of an additional 64,000 bytes of high-speed core on the 360/50. The effect of the high-speed core addition was to cut compilation time in half. This also reduced the effective page minute or core residency charges by providing users with more efficient computing. In recent months the system appears to be achieving a new equilibrium described in more detail below in the section on utilization. In June, additional core for the 1800 will be ordered as will some additional CRI's. Throughout the year, the staff emphasized tasks which would improve hardware and software reliability. Organizationally, two changes occurred in the past year. A new subcommittee to the ACME Policy Committee was established to serve as a short and long-range plan review group. This subcommittee consists of Dr. Elliot Levinthal, Dr. Edward Grant No. RR 311-04 Section II-A Feigenbaum, and Mr. Gio Wiederhold. In May, 1970, Mr. Ron Jamtgaard was appointed Director of the ACME Facility. In late May, the staff of ACME began an evaluation of various methods of providing desired expansions to standard services. A key question involved is the basic approach of adding one medium-sized satellite processor to handle a variety of functions versus multiple mini-computing systems each handling one or two functions. The study was extended into June, thereby missing the dead- line for this report. Some of the incremental services being considered are: multiple processor access to 2314 disk files; expansion of available 271 ports; back-up or redundant capacity for recording data from real-time data-acquisi- tion users; various fail-safe devices for terminal users; and allowance of considerable expansion room in the field of graphics in terms of central hardware. This Annual Report covers the period August 1, 1969 through May 31, 1970, plus estimated operating results for the period through July 31, 1970. ACME was created in July, 1966, under a three-year grant from National Institutes of Health, Special Research Resources Branch. The initial goal was to provide a time-shared computer facility and real-time, data-acquisition system for research groups within the Stanford Medical Center. A second three year grant was approved by NIH in August, 1969. The primary goal of the second three- year grant has been improvement of reliability of both hardware and software. The facility is administered by the Stanford Computation Center under the direc- tion of Paul Armer. The ACME System achieved the initial goal with considerable success. There are over 200 projects presently on the system operating from some 50 terminals in the Medical Center. In addition, there are twenty-one (21) laboratories connected to ACME for real-time data-acquisition and process control. Grant No. RR 311-04 Section [I-A ACME's hardware consists of an IBM 360/50 with a 2-million byte extended core storage, plus an IBM 1800 processing unit used for data-acquisition and control of graphics devices. The language used is a subset of PL/1 which was chosen for its power and ease of learning. For more details on tasks accomplished during the past year and new "core research" tasks started, refer to Description of Core Research Activities on page 9. SOME GOALS AND ACCOMPLISHMENTS OF PAST YEAR: SOFTWARE RELIABILITY: In the grant proposal one year ago, it was noted that software failures stem mainly from interface problems between IBM's Operating System and the ACME system, error recovery procedures within OS, unanticipated user demands, etc. Failure rates were shown to be dependent on the rate of change of the software system. At that time, approximately one-third of the total system failures were caused by software. One plan for the new grant period was to reduce the number of modifications to the system by taking advantage of the existing structure to meet new requirements. In practice, this intent has been only partially satisfied. New software has been added to the system using the basic structure (a command "Show Undefined", graphics control soft- ware for "add on" graphics units to be used in conjunction with 2741 typewriter ter- minals; ete....) However, some changes have called for modifications to the basic structure: software for the link between Campus Facility 360/67 and the ACME system, and a new communications software package for the 1800. The goal was to improve the system to a point where software would be responsible for system failure no more often than once every two to three weeks. Despite much effort on this activity over the past nine months, software accounted for 10 failures between mid-April and mid-May. The effort will continue. Grant No. RR 311-04 Section IT-A HARDWARE RELIABILITY: The proposal cited three specific hardware boxes which had caused an inordinate number of system failures -~ 2702 transmission control unit, 7720 adapter for the 1800, and the 270X-Y high speed data transmission units. The problems involving the 2702 device appear to have been solved. This unit has failed only three times in the past year and has operated without failure for the past nine months. The 7720 adapter for the 1800 continued to provide some problems until a software solution was implemented. In addition, a number of recent crashes of the 1800 system have been traced to the input/ output hardware. The cause of the problem remains unidentified. 17,402 3,023 20,425 Travel 4,000 4,000 ---- 4,000 1,000 5,000 Publications Costs 5,000 4,000 <1,000> 4,000 1,000 5,000 Engineering Services ---- 9,500 9,500 15,000 5,000 20 ,000 Computer Services 10,000 10,000 ---- 10,000 10,000 IBM S.E. Service, Program Products, Staff Training 16,380 1,000 <15,380> 1,500 1,500 2,500 5,500 Other 7,973 8 350 37T 8 ,600 8 600 TOTAL DIRECT 700,000 700 ,000 750,000 42,900 47,100 840 ,000 INDIRECT@57/59% 112,689 118 ,182 153,611 TOTAL OPERATING costs 812,689 818 ,182 993,611 Service Charge BUNDING Income Estimate 100 , O00 170,000 220,000 SRR Support 712,689 712,689 709,104 Requested Carryover to RR 311-05 <6L ,507> 64,507 TOTAL FUNDING 812,689 818,182 993,611 Grant No. RR 411-04 Section ITI-D Budget Justification The table on the preceding page presents estimated costs for the current fiscal year (both as awarded and an updated estimate). It also presents the original estimate for FY19/1, and a current estimate for the coming year which starts August 1, 19/70. In summary, ACME expects to spend $700,000 in direct costs in the current year and to receive user fees or income of about $170,000. For next year, costs are estimated at $750,000 for the base program plus an additional $90,000 for desirable budget restorations and contingency items. The budget justification material presented below contains three parts: (1) changes between amounts awarded and amounts to be expended in current year by budget elements; (2) review of base program requested for next fiscal year; and (3) explanation of proposed additions to base budget for next year and contingency items. The major variation in expenditures for the current year is found in the part of the award allocated for services by IBM personnel as a result of IBM's un- bundling. The Stanford Computation Center has adopted a position which does not permit acceptance of the IBM service engineering service agreement under its cur- rent restraints and conditions. Further, the IBM Service Engineer who has been servicing ACME's support needs, was transferred to the marketing group. ACME did receive some assistance from the former IBM Service Engineer, but was forced to use some of its own staff time to maintain the system software. S. E. Service on IBM's Operating System continues to be given without charge. The IBM S. E. service, programs, products, and staff training were budgeted to cost $16,380, but will result in less than $1,000 in actual cost. A second major change area involves engineering and technician services. In the past, ACME employed its own engineer and technicians. During the past year, ACME elected to use the services 5u Grant No. RR 411-04 Section III-D of the Engineering Services Group attached organizationally to the Stanford Computation Center. These services are no longer budgeted under "salaries"; a new budget category of "Engineering Services" has been added. Finally, the funds originally budgeted for a second interactive graphics unit have been applied to the purchase of three add-on graphics units plus an input/output device control system. This equipment acquisition is the subject of separate correspondence in which N. I. H. approval is being sought at present. Revenue from service charges in FY1970 will exceed the estimates prepared one year ago by approximately $70,000. Last July, user charges were estimated at $100,000 for the-O4 year. This estimate was made on a highly conservative pasis since this was to be the first full year of user charges and the impact of such charges was not known. During the past fiscal year, most of our users have become eligible to pay on the anniversary date of their grants. In the first half of the year, it became apparent that the original estimate was too low. A major rate decrease was made effective mid-February 1970, this gave some relief to the researchers whose grant funds had been reduced from earlier ex- pectations. During May, 1970, ACME received income of approximately $14,000. Therefore, much of the effect of the rate reduction has been offset by increased utilization by paying users as well as an increase in the number of paying users. The ACME renewal proposal included a budget for the second year of the three- year renewal amounting to $812,000. The Site Review Committee and N. I. H. Research Council have recommended that ACME be supported at a level of only $750,000 in Year 5. Therefore, a base budget of $750,000 has been prepared; however, it must be emphasized that some incremental funding over the $750,000 level is deemed essential in order for ACME to achieve a reasonable number of the goals established in the renewal proposal and to fulfill the requirements set down by the ACME users. D9 Grant No. RR 311-04 Section III-D The base budget of $750,000 fails to provide adequate funding from ACME's viewpoint. If no more than this cost level were made available, the core research activities would suffer. ACME's top priority must now be placed on serving a community of users; and the development of new facilities and structures will have to be assigned a relatively lower priority. Also, the base budget permits no expansion of hardware facilities to accomodate growing user demands. (One minor exception to this statement is the purchase of additional core for the 1800 system which has been retained in the base budget because of the extreme need for added 1800 core for real time users.) A desirable budget for ACME for the next fiscal year (FY1971) would be $840,000. This level of authorized cost ceiling would provide $42,900 for personnel, services, and supplies for development activities and expanded operating hours, and $47,000 for so-called "contingency" items. The items associated with each of these figures are presented below. In order to reduce the "desired" budget level to the base budget level, the following personnel costs were with- drawn: System Programmer $15 ,400 User Consultant (1/3) 4,262 Research Assistance 3,564 Secretarial Assistance 1,000 Computer Operators (for two added shifts per weeek) 2,915 subtotal, salaries 27,141 Staff Benefits on Above 3,736 Total, personnel $30,877 The system programmer position identified above would constitute a reduction from present staff, or a redirection of charges to a user group. It is questionable whether alternate funding could be found in the current tight money situation. One-third of an exisiting full-time user consultant has been withdrawn from the base program budget with the assumption that his time will be charged to users' projects. The research assistance item would cover the hiring of graduate student assistants to help with various development tasks at ACME. Historically, such 56 Grant No. RR 311-04 Section III-D student help has been found to be highly productive and creative. The secretarial assistance item reflects a part-time position created during the last year to reduce the amount of clerical work for the professional staff. The tight budget situation will cause elimination of this part-time pesition with the consequent transfer of clerical functions back to other staff. Finally, the additional shifts of operator coverage have been withdrawn. It was intended that the grave- yard shifts on Sunday and Monday mornings would be covered during the coming year. As evening and nighttime use by users increase, it will become increasingly necessary for system functions to be performed on weekends and for the users' data on ACME to be available around the clock. Other budget cuts from a "desired" budget level, exclusive of contingency items, were: Outside Consulting $ 500 Travel 1,000 Publications 1,000 Engineering Services 5,000 IBM Products and Services 1,500 Supplies 3,023 Bie.003 These were arbitrary cuts made in order to get the budget level down to $750,000. The most significant two items involve engineering services and IBM products and services. The engineering services budget has been cut from $20,000 to $15,000. It is likely that this leaves adequate funds for maintenance functions but nearly zero funding for development tasks. The IBM product and service budget items covers customer engineering service, system engineering service, and IBM educational courses. One system programmer course which we would like to make available for a staff person costs $2,500. This one course is highly recommended but has not been budgeted specifically. The education courses generally cost $80 to $150 for three to five day courses. The major six week course costing $2,500 will be incorporated in the contingency budget. Grant No. RR 311-04 Section III-D Contingency items which ACME feels should be included in the FY1971 (RR 311-05) budget include the following: Added on-line storage (such as data cell and control unit, rented for six months) $18,800 Second 2701 to accomodate added real time users or special devices (6 months rent) 5,800 Three additional "add-on" graphics units and interface hardware 15,000 Portable typewriter terminal and modems 5,000 Sub Total Equipment 44 5600 System Programmer six week course 2 500 Total $47 ,100 The added on-line storage device would supplement the two existing 2314 disk drives. It is assumed that normal system growth will result in need for some additional storage capacity within one year. The exact timing of this need is difficult to predict. The second 2701 device is likely to be needed within six months. The present 2701 device has four ports of which three are now used regularly. Support for new devices such as strip printers, mark sense readers, etc. would require additional port capacity from 2701's. In addition, satellite computer systems would likely be connected to the system via a 2701 port. Three "add-on" graphics would simply expand the number of public graphics terminals available to the users. The portable terminal and modems would prove useful for both staff and users of ACME. The portable terminal would facilitate work at home on evenings and weekends as well as presentations to prospective users of the system in their laboratories. ACME proposes to use FY1970 income in excess of the $100,000 estimate to fund the non-contingency additions to the base budget level as well as the contingency items identified above. Income for FY1971 (RR 311-05) would amount to $180,000 if the average monthly user fees were equal to May, 1970 fees. Some increase in paid usage appears 58 Grant No. RR 311-04 Section III-D reasonable based upon overall utilization history. Therefore, ACME projects user fees for page minutes and disk storage at $220,000 for FY1971. Some attempt has been made to allow for rates, the tight money situation, user eligibility to accept charges in FY1970, normal usage growth, and resource capacity in making this estimate. Grant No. RROOZ11-04 Section IV Category 1 Name: Anderson, D. Project: JOAN Department: Genetics Project Description: The project involves instrumentation and control of a mass spectrometer using a time-shared computer system interfaced with smaller data gathering devices, Name; Bacon, V. Project: GAME Department: Genetics Project Description: Data ecdilection, storage, analysis from Finnigan 1015 mass spectrometer. In this on-line project, the decision making capa- bilities of the computer are coupled with those of an operator to direct the operation of a Finnigan 1015 quadrupole mass spectrometer. The computer is used to actively direct the operation of the mass spec- trometer by controlling the mass filtering system of the instrument. It is used to recognize and control the voltage changes which define mass peaks and enable the rapid collection and presentation of data, The computer traces out peak shapes of the known masses in a reference gas allowing the operator to determine correct mass positions, and to enter any shifts in calibration into the computer register for compensa- tion automatically. While taking data, the information may be displayed on an oscilloscope or recorded on magnetic tape. Once data is acquired, the structural identification of organic compounds is made from orthogonal coordinate or spiral base plots of mass spectra made by computer direction of a calcomp plotter. The system is also used to analyze gas liquid chromato- graph effluent permitting the structural identification of mixtures of organic compounds. Stored data offer the future possibility of spectra matching of unknown compounds. 29 Grant No. RROO411-o4 Section IV Name: Bridges, J. Project: JOY Department: Genetics Project Description: Write programs to control a quadrapole mass spectrometer; collect, manipulate, and plot data from same. Name: DeGrazia, J. Project: CLINIGAS Department: Nuclear Medicine Project Description: This project supplements a second project, RADIOGAS, whose purpose is the development of a project co-ordinating the use of a computer with an instrument called a metabolic gas analyzer. In contrast to RADIOGAS which will be used primarily for program development, this project will provide for the routine handling of patient data from studies where program development has been basically completed. This will allow us to account for our patient computer time independently of RADIOGAS. Name: Hanawalt, P. Project: TRI CARB Department: Biological Sciences Project Description: The project involves the use of radioisotope tracers in studies of the molecular biology of cell growth and repair of damage to genetic material. Materials studied include normal and malignant human cells in culture as well as polio and adeno-viruses and various other virus and bacteriophage systems important to medical research. 60 Grant No. RROO411-04 Section IV Name: Harrison, D. Project: CATH _LAB Department: Cardiology Project Description: An extensive cardiac catheterization data analysis program has been developed. Statistical analysis of the results ob- tained by the computer justify routinely using such a program on a day- by-day basis for calculation of the results of cardiac catheterization. This would greatly decrease the amount of time a physician need spend after the catheterization in analysis of the data. Because of the time required to complete a catheterization, the large size of the program and the fact that it is resident in core while data is being collected, serious consideration is now being given to the use of digitally coded magnetic tapes which may be played back after the completion of the catheterization. This would result in decreased computational cost. In addition, other catheterization laboratories in the area may then be in a position to utilize such a program, Given the necessary computer reliability to routinely analyze catheteri- zation data, a program is available to automatically transfer the results of computation to a patient record in a data file. Forms are available which will be used to obtain clinical, X-ray, EKG, and surgical followup data permitting statistical correlations on a large group of patients. ACME is also being used to develop a program for recognition of abnormal EKG complexes. In the near future, we hope to be able to use such 2 pro- gram in a computer devoted to monitoring of Coronary Care Unit patients. In view of the cost of the analysis of a complete cardiac catheterization, new programs are being developed for a small computer system to carry on the same type of analysis of the catheterization data as was originally programmed in the ACME system. These new systems will be compared for accuracy and reproducibility with the old system presently being utilized under the ACME Facility. 61 Grant No. RROO411-04 Section IV Name: Jones, R. Project: FLU Department: Biochemistry Project Description: Work with ACME centers around a nanosecond fluormeter designed by Stryer, et. al. which measures kinetics of fluorescence as a function of time directly. Data acquisition is accomplished through the 1800, and subsequent data reduction is carried out in the 360/50 proper. The instrument as a whole has been used to determine 1) excited state lifetimes of various organic fluorescent componds; 2) rotational relaxation times of various proteins, using fluorescent labels to determine rotational behavior of the protein in both natural and denatural states; and 3) excited state proton-transfer reactions. Name: Kennedy, D. Project: NERVOUS Department: Biological Sciences Project Description: Perform several basic methods of analysis of neuro- physiological data: 1) preliminary conversion of analog to digital form of neuronal data, 2) reduction of these data with tabulation and graphical display, and 3) statistical treatment of the data, including visual display of the results. Further simulation and modelling of neuronal systems are also planned on ACME, including Monte Carlo and deterministic models. Proposed research involving ACME is directly related to an understanding of the nervous system. All results support and supplement most medical/ clinical aspects of neurophysiology. Name: Lederberg, J. Project: NOHANDS Department: Genetics Project Description: Research and development in methods of automating the operation and service on the Finnigan 1015 mass spectrometer in the IRL exobiology labs. 62 Grant No. RROO411-04. Section IV Name: Lederberg, J. Project: LEARN Department: Genetics Project Description: Program instruction; work area for programming and instrumentation use practice. Name: Liebes, 58. Project: MS Department: Genetics Project Description: This project is directed toward the development and application of techniques of high-spatial-resolution mass spectroscopy to organic materials of biological interest. The current investigation involves the use of focused radiation from a pulsed ruby laser to vaporize portions of solid samples in the ionization chamber of a Bendix Time-of-1Flight mass spectrometer. The plume of vaporized material is ionized by electron bombardment, and the time evaluation of the mass spectra of these ions is monitored at a 10-kc/sec repetition rate. The materials so far studied include amino acids, the nitrogenous base constituents of DNA, samples of DNA, nucleohistone, Lymphocytes, fibroblasts, and red blood cells. We are moving now to the comparison of normal versus abnormal blood and tissue samples. The ACME Computer Facility serves the following important supportive functions: 1. Automation of data acquisition. 2. Storage of all derived mass spectral data. 3, Manipulation and comparison of data~-certain aspects of these operations involve extensive use of the interactive television graphic display. 4. Performance of analytical studies related to the interpretation of data, the refinement of existing instrumentation, and the development of new apparatus. 63 Grant No. RROO411-0}4 Section IV Name: Reynolds, W. Project: S007 Department: Genetics Project Description: This project supports the basic development of automated mass spectrometer and other instrumentation systems. The mass spectrometer has become of interest in the biochemistry field. In the case of DNA and related structures, the basic principles involved are common to at least the Genetics Department and to the Organic Chemistry Department. Hence the efforts of this project span over five mass spec- trometers in three diverse locations on the Stanford campus. The technical development consists in the origination of instrumentation concepts and the realization, in both hardware and software, of complete operating systems. These systems are intended to automate the mass spectrometers (low reso- lution Bendix t-o-f, Finnigan quadrupoles, Atlas CH-4, and a high resolu- tion AEI MS-9) and to provide the following benefits to the biological user-researcher: Saving of the researcher's time in instrument operation and.data reduction, and improving the quality of the data, improving the presentation of the data, and fostering computer files of pertinent data. This is being accomplished by basic research and development in the ap- plication of computers, both dedicated and time-shared in the field of computer-instrument integration. The ACME system is being used as the final computer in the automated system and as an engineering design aid to achieve the final systems. Some phases of this development are in current use. In these cases the usage is sup- ported by other projects, i.¢., VABACON.GAME,. Grant No. RROO311-04 Section IV Name: Stryer, Il. Project: NANOS Department: Biochemistry Project Description: The principal aims of the research are: (1) to acquire an understanding of mechanisms of electronic excitation’energy transfer, (2) to develop novel fluorescence and phosphorescence methods which can provide detailed information concerning the structure and dynamics of biological macromolecules, and (3) to apply these optical techniques to obtain insight into aspects of the structure and function of selected proteins. The experimental approach which is used in these studies involves: (1) the synthesis of model compounds which serve to define relationships between observable emission parameters and structure, (2) the synthesis of fluorescent and phosphorescent labeling reagents which have appropriate spectral properties and can be specifically attached to defined sites on proteins, and (3) the development of optical instrumentation of kinetic measurements in the nanosecond time range and for the detection of fluor- escence and phosphorescence emission from membranes and cells. Name: Tucker, R,. Project: MS Department: Genetics Project Description: The project consists primarily of developing a com- puter system for the control of a quadrupole mass spectrometer-GLC apparatus and the collection, analysis, and presentation of the re- sulting data. This system utilizes the 1800 computer to transfer control data from the 360/50 to the mass spectrometer and to digitize the output of the mass spectrometer for storage in the ACME file system. This bidirectional data flow results in the mass spectrometer being "set" to successive predetermined position rather than scanned in the conventional manner. The data is presented to the user in the form of tabular listings and bargraph plots produced by a digital plotter lo- cated in the laboratory and driven by the 1800. 65 Grant No. RROO411-04 Section IV Name: Wilson, D. Project: NERVOUS Department: Biological Sciences Project Description: Use ACME in order to perform several basic methods of analysis of neurophysiological data: 1) preliminary conversion of analog to digital form of neuronal data, 2) reduction of these data with tabu- lation and graphical display, and 3) statistical treatment of the data, including visual display of the results. Further simulation and model- ling of neuronal systems are also planned on ACME, including Monte Carlo and deterministic models. Proposed research involving ACME is directly related to an understanding of the nervous system. All results support and supplement most medical/ clinical aspects of neurophysiology. Name: Yguerabide, J. Project: LUM Department: Biochemistry Project Description: Same project description as for L. Stryer, Biochemistry Department, project NANOS. 66 Grant No. RROOS11-04 Section IV Name: Zwick, M. Project: CRYSTAL Department: Biochemistry Project Description: This project concerns the development of new theoretical techniques for the solution of protein crystal structures. The method currently used, "isomorphous replacement," generally requires a team of scientists working for a number of years with no guarantee of success. This method has the surprising feature that it makes virtually no use of a great deal of a priori stereochemical information about proteins: e.g., the bond distances and angles of the repeating pephile unit in the protein backbone or on the amino acid side-chains. Hence it is very plausible that new improved methods might be developed which utilize such information and which can solve protein structures much more rapidly and easily. In this project, attempts are being made to define a new set of variables which can specify the protein structure, which is much smaller and hence more easily determinable than the set of atomic coordinates. This new set of variables might conceivably be determinable simply from the X-ray intensities of the native crystal, i.e., isomorphous derivative may not be required. The new set of structure variables are designed to implicitly include the fact that a protein is a linear polymer folded up in some manner in three dimensions, and that this polymer has a set of well known bond distances and angles in its repeating unit and in its branching side chains. 67 Grant No. RROO311-O4 section IV Category 2 Name: Atkinson, M. Project: FLYHIGH Department: Stanford Medical School - Admissions Committee Project Description: This project is a series of programs to assist the Admissions Committee in selecting new Medical School classes, The programs all work off of one large file which contains information on the applicants. Included in the programs are file creation and update, listing, and sorting programs. The sorted listings are then used by the Committee to aide in decision making. Name: Bagshaw, M. Project: PLAN Department: Radiology Project Description: Research is under way, and we hope to be able to use ACME to provide the radiation therapists with: 1) external beam treatment plan- ning, 2) interstitial and intracavitary dose calculation, and 3) data ac- cession and retrieval. Name: Bergstresser, Pp, Project: FLOW Department: Dermatology Project Description: Compute blood flow in fingers and toes. The values are derived from experimental data and converted to flow, expressed in ec/ min/100cee digit. 68 Grant No. RROO311-o04 Section IV Name: Brown, B. W. Project: CONSULT Department: Community & Preventive Medicine Project Description: Computations done in support of a multitude of public health research projects. Name: Brown, B. W. Project: RESEARCH Department: Community & Preventive Medicine Project Description: Development of new biostatistical techniques. Name: Brown, B. W. Project: BIOSTAT Department: Community & Preventive Medicine Project Description: Conduct various statistical computations in support of research carried out by members of the Department of Anesthesia under their Program Projects Grant from NIE. 69 Grant No. RROO311-04 Section IV Name: Crowley, L. Project: WNDSTUDY Department: Surgery Project Description: Study of results of antibiotic agents instilled into wound at time of surgery to reduce infection rate of general surgery patients. Name: Durbridge, T. Project: ROOT Department: Pathology Project Description: 1) Statistics: using ACME subroutines, programs, and minimal own coding to compute statistics for S.V.H. research projects. 2) Pathologese S.N.O.P. translation: working with Derek Enlander on same, Name: Enlander, D. Project: e¢1050937 Department: Clinical Lab Project Description: Back-up routines for the clinical lab computerization main project. These routines will consist of statistical analysis of the data generated in the clinical lab, Name: Fletcher, G. Project: DIALYSIS Department: Anesthesia Project Description: Statistical analysis of laboratory results from in- vivo and in-vitro studies of uptake, metabolism, and elimination of seda- tive drugs. 70 Grant No. RROO411-04 Section IV Name: Forrest, W. Project: ANALGESI Department: Anesthesia Project Description: Same project description as for project DATA. Name: Forrest, W. Project: DATA Department: Anesthesia Project Description: We use the 360/50 time sharing real-time system to research the management and statistical application of methods to the Cooperative Study. Problems of pilot studies, data validity, quality, cost of clinical trials and useful reduction of data for active sane management are constantly evaluated and updated. The plan is to develop an inexpensive system of quality and quantity control of large masses of clinical data from several sources so that data diarrhea and "gigo" are diagnosed properly and treated prophylactically rather than symtomatically. Name: Grindle, J. Project: ROSAN Department: Community & Preventive Medicine Project Description: The purpose of this project is to correlate the lab- oratory and clinical findings in newborn infants with respiratory dis- tress syndrome who have been treated with oxygen and mechanical ventil- ation. This is a new and unusual group of infants whose natural his- tories have been significantly modified by treatment, and who have a disease due in part to oxygen toxicity. The disease was first discovered at Stanford by Dr. William Northway (Radiology) and Dr. R. Rosan (Pathology). In this analysis, we seek to correlate the oxygen doses, clinical his- tories, and biochemical analyses of the endobronchial secretions. The latter analyses, result of a technic also invented at Stanford by our group, include DNA/protein ratios, distribution of DNA and protein in soluble and insoluble fractions of secretions, and gel acrylamide dis- continuous electrophoreses of the fractions. The aim of the computer- assisted study is to set up a matrix covering the principle parameters and variables in order to permit extraction of the most significant correlations, The number of elements and categories in the matrix is too large to permit of conventional treatment, This is particularly true for the electrophoreses, there being some 163 possible band positions in the system studied with the resolution used. Therefore, use of the com- puter is essential in extracting the most significant and useful in- fi formation from this study of human patients. Grant No. RROO411-04 Section IV Name: Hilf, F. Project: BLACKBOX Department: Psychiatry Project Description: We are conducting a study in which paranoid and non- paranoid psychiatric patients are tested on-line with the ACME computer. The patients are presented with stimuli in the form of character strings and are prompted for responses. Reinforcement is non-contingent at several different probability levels. An analysis of responses will be conducted to see if this method is useful in differentiating paranoid from non-paranoid patients. Name: Hogness, D. Project: OREGON-R Department: Biochemistry Project Description: Analyze experimental data. Use ACME in recognizing chromosome fragments in Drosophila. That is, being able to recognize a linear band--interband pattern and compare it to know patterns to determine the fragment's location, i.e., the chromosome from which it came, Name: Huberman, J. Project: TEMPLATE Department: Biochemistry Project Description: Using ACME to perform the lengthy and tedious calcu- lations required to reduce the raw data obtained in equilibrium dialy- sis experiments to a meaningful form. I am performing equilibrium di- alysis experiments with the enzyme, DNA polymerase, and various nu- cleotide substrates, in order to get a better understanding of the active site of the enzyme. Using equilibrium dialysis, it is possible to answer such questions as--What kinds of molecules bind to DNA poly- merase? How strongly do they bind? How many binding sites does each enzyme molecule have? The answers to these questions help in under- standing the structure of the’active site of DNA polymerase and its mechanism of action. fe Grant No. RROO311-o04 Section IV Name: Kohen-Raz, R. Project: ATAXTAM Department: Pediatrics Project Description: Diagnosis and treatment of statis balance impairment in. educationally handicapped school children. Data processing will include analysis of electronic ataxia metric data, as well as analysis of simultaneous recordings of ataxia-grams, EMG and ERG. Name: Koran, L. Project: SEX Department: Psychiatry Project Description: We plan to use ACME to complete one, two, and three-way analyses of variance on test scores made by one thousand students. We wish to explore the relation of these scores to a number of variables including sex, class of college, size of home, major field, religion, and other demographic information. After completing the analysis of the data, we plan to write two articles on the relation of the students identifying characteristics to their knowledge as measured by the exam. 15 Grant No. RROO411-04 Section IV Name: Kountz, 8S. Project: KIDNEY Department: Surgery - University of California Project Description: The ACME computer is used by the Transplant Service at the University of California in two areas. The first area is the selection of recipients for renal homotransplantation, and the storage and analysis of data from the follow-up on the degree of renal function in an effort to predict the onset of rejection crisis. The computer has been programmed to include sixty or more patients in the Bay Area who are on cronic hemo- dialysis awaiting a cadaver transplant. Their ABO blood groups and their HLA antigens are stored in the computer. When a cadaver kidney becomes available, similar tests are performed on the donor; the kidneys are pre- served and the information on the donor is fed into the computer and the matched recipients are then selected and brought into the Hospital for transplantation. The second area is to measure and calculate hemodynamic changes in transplant patients as a means to detect early incipient rejection. Renal function is measured by the single injection of radioc- isotopes and the disappearance curves are analyzed by the computer and compared with previous determinations. This has provided a very accurate method of following patients and detecting early incipient rejection. In the future we hope to feed all this information into the computer and analyze it in terms of survival in an effort to pick out which HL-A anti- gens or other factors might be playing a significant role in rejection as well as survival. Name: Kraemer, H. Project: PSYSTAT Department: Psychiatry Project Description: The work done in PSYSTAT is that of developing statistical programs and evaluating sets of data coming from research where output is not extensive enough to justify opening a separate file. 7 Grant No. RROOZ11-o04 Section IV Name: Lederberg, J. Project: DENDRAL Department: Genetics Project Description: This project is used to do limited generating chemical structures and display on Sanders 720 by interfacing. Name: Levinthal, F. Project: MM/71 Department: Genetics Project Description: We are just initiating efforts to use ACME for photo- interpretation, The direct application is for the 1971 Mars Mariner Orbiter Mission. The photointerpretation techniques will be appli- cable to medical research problems as they have already been at the Jet Propulsion Laboratory. Name: Lieberman, M. Project: RACE_GEP Department: Psychiatry Project Description: Project involves the measurement of the efficacy of "small groups” in education. Relevancy of statistical test will yield hypothesis testing of various such efficacies. 7) Grant No. RROO311-04 Section IV Name: Liebes, S. Project: MV73 Department: Genetics Project Description: In support of a proposed involvement, on the part of members of the Department of Genetics, with the imagery system to be landed on the surface of the planet Mars in the course of the Viking 1974 Lander Mission. The camera system will be utilized for scientific exploration of the Martian surface and atmosphere. Investigations will particu- larly be directed toward the elucidation of the petrographic char- acter of the Martian surface and extant or extinct biota. Initial effort will be devoted to design aspects of the camera system and an augmented microscopic capability. Name: Liebes, S. Project: MM71L Department: Genetics Project Description: Investigating means of data processing for interpre- tation of photographic data from the Mariner Mars 1971 Orbiter program. Principle focus at the present is on analogue optical data processing by use of coherent light techniques. 76 Grant No. RROO311-04 Section IV Name: Lorenson, M. Project: PFK_1 Department: Pharmacology Project Description: A portion of the research work carried out in this laboratory is on the sheep heart enzyme, phosophofructokinase. Investi- gations are being made on the binding of carbon-14 labelled ligands to the enzyme. It is hoped that from these data, information will be gained on the molecular mechanisms by which this enzyme and possibly carbohydrate metabolism are controlled and regulated in vivo. The method being used involved chromatography on G-25 Sephadex columns which have been equili- brated with the radioactive ligand. In order for a thorough study, large numbers of columns must be run. Statistical analyses must be made on a large number of fractions including (1) calculation of radio- activity present; (2) specific activity of ligands; (3) determinations of units of enzyme activity; (4) determinations of protein concentrations and specific activities; (5) and binding and the standard deviations involved. In addition, the data are summarized and related to the concentrations of unbound ligands. If the computer were not used for these calculations, the information to be gained would be difficult to compile and the research work would be slowed considerably. Name: Luzzatti, L. Project: GRAGSON Department: Pediatrics Project Description: Programs previously utilized for statistical analysis of chromosome measurements in a family with chromosomal abnormalities are now being used for an ongoing study of the morphology of the late replicating X chromosome. Programs are also used for another ongoing study of synchronization of human lymphocytes in culture. The use of the ACME computer for the study of children with birth defects continues. In addition, a program is now available for the storage of anthropometric data on all patients with congenital defects. A study of anthropometric measurements and dermatoglyphic patterns of sixty children with cleft lip and/or palate, utilizing the data stored in the computer and computer-assisted statistical analysis, has been recently completed. By using computer information, we have been able to define certain characteristics of body configuration in children with clefts. Further similar studies in other syndromes are now in progress. T7 Grant No. RROO311-04 Section IV Name: Maffly, R. Project: C02 Department: Medicine - Lipid Research Project Description: Under study is active sodium transport by the toad bladder. We correlate three variables: short circuit current, CO production, and C” 0, production. The computer is used to calculate the variables and to interrelate them, and to perform statistical analyses, T plan to collect data on patients with elevation of blood urea nitrogen and with decreased serum sodium concentration and to use the computer to find out the predictive value of a variety of tests and procedures and laboratory data. Name: Maffly, R. Project: TEACH Department: Medicine - Lipid Research Project Description: Develop programs which can be used to educate medical students, house officers, and fellows in the principles and practical aspects of water and electrolyte problems which occur in patients. Develop programs dealing with disorders of serum sodium concentration and serum urea nitrogen concentration. We have begun with a program obtained from Dr. William Schwartz of Tufts University Medical School dealing with the evaluation of acid-base disorders: data on individ- ual patients are presented to the computer by the student and the computer responds with physiologic interpretation, therapy, logic, and references, 78 Grant No. RROO311-04 Section IV Name: Miller, R, Project: STRABTS Department: Community & Preventive Medicine Project Description: Define the relationship of various parameters to the results of strabismus surgery. It is our intention to generate, even- tually, a mathematical model representing the likely result of any com- bination of findings in such a strabismus patient. Furthermore, these data will be eventually organized to ascertain the most satisfactory strabismus operation for any set of findings. To date, valuable new relationships have been established in the rela- tionship of size, of the strabismus deviation as compared to a result obtained from surgical correction of the deviation, and in the linear relationship of the effects of tightening muscles as compared to loosen- ing muscles for strabismus. Numerous other linear correlations have not been immediately identified as important ones, but they and other par- ameters will be evaluated as the study progresses. This is an approach which is tedious and time consuming, but appears to offer a major improvement in result of strabismus surgery, a field where re-operations are required in one-third of the cases because of the inaccuracy of assessing data originally. 79 Grant No. RROOZ11-0}. Section IV Name: Nall, M. Project: PSORTASI Department: Dermatology Project Description: Psoriasis is a chronic, scaling skin disease of unknown etiology, which affects approximately 4% of the general population (no accurate figures are available). It is a lifetime disorder which does not take life, but indeed distroys it for all age groups. The Department of Dermatology of the Stanford Medical School is a world center for both clinical and laboratory investigations on psoriasis. As one phase of the over-all Psoriasis Research Program, the Department is engaged in a continuing investigation of the epidemiology of the disease. A questionnaire survey has been conducted from 1959 to date. Presently, the Department is conducting Series II, III, and IV of its questionnaire survey; doing follow-up studies on the familial incidence of psoriasis and the relationship of psoriasis to other diseases, i.e., arthritis, diabetes, throat infection (The findings from Series I, which had been computerized on the 7090 are now being handled by the 360/50 and 67.). We have applied to the National Research Council to participate in their Twin Registry of Veterans, in order to utilize the twin method in our study of the etiology of psoriasis. In addition, we are applying to utilize their registry of veterans in a large scale epidemiology investigation. 80 Grant No. RROO411-04 Section IV Name: Nall, M, Project: MYCOSIS Department: Dermatology Project Description: Mycosis fungoides is a fatal skin disease of unknown etiology. Various chemotherapeutic agents (i.e., nitrogen mustard, steroids, etc.) have been utilized to abate this disease, but the X-ray and electron beam are the only techniques that have proven ef- fective in producing remissions. The Stanford School of Medicine and the Massachusetts General Hospital are the only facilities in this Country, who have applied the beam in treating mycosis fungoides; although recently the Varian Company has developed smaller accelerators which will be used in other hospitals. Drs. Harold Schneidman and William Watson of the Dermatology Department conducted a retrospective study on the effect of the electron beam in comparison to other methods of treatment. In a pilot study of 51 mycosis patients (treated at the Stanford Medical Center in the Radiology Depart- ment), the investigators developed a data gathering form. The coded information was keypunched and read into ACME as a data file, which was computed via a number of input-output programs. The investigators were able to learn from their preliminary study that by applying the electron beam at an early stage of the mycosis that longer periods of remission will result. Name: Nye, W. Project: STUDENT Department: Medicine - Micro Project Description: Under this user name, several people in the Department have used this project for statistical calculations and bibliography compilations. Several of the users have been graduate students of the Department or postdoctoral fellows. 81 Grant No, RROO411-04 Section IV Name: Petralli, J. Project: MED DATA Department: Medicine - Infectious Diseases Project Description: To improve the quality of antibiotic sensitivity data (high potency single disc method) and to guide the interpretation of re- sults and antibiotic selection a computer program has been developed. Clinical information and zone sizes are entered into the ACME computer each day. Each zone size is compared with limits based on previous re- sults and unusual values are challenged for further study. This system converts zone sizes to resistant, intermediate, or sensitive and prints final reports from its memory. Decreased potency of antibiotic disc is detected by comparison of periodically determined mean zone sizes. Limits of confidence of a single reading are established by review of zone sizes observed with a standard organism tested on different occa- sions. Knowledge of antibiotic sensitivities of organisms isolated from a specific site such as blood or urine will help to guide the selection of antibiotics before specific sensitivities are known. Such information is of value in selection of antibiotics in treating rarely encountered organisms with less well known sensitivity patterns or in selection of alternate antibiotics when the first choice drug is hazardous. Yearly comparison of antibiotic sensitivity patterns obtained will give infor- mation about major trends and suggest appropriate changes in treatment of various infections. Name: Reynolds, W. Project: TEXTS Department: Genetics Project Description: This is a text management project to support general engineering efforts in instrumentation. The project supported is: W. E. REYNOLDS.SOO7. "TEXTS" contains commercial technical data and information retrieval programs. &e Grant No. RROO311-04 Section IV Name: Rosenberg, L. Project: ALEXINE Department: Medicine - Micro Project Description: We are studying levels of serum complement in mice using ACME to carry out the appropriate statistical analyses and calculations. We are storing accumulated data on large numbers of mice of diverse pedigree. Using ACME facilitates data retrieval. Name: Schneiderman, L. Project: PATCHART Department: Medicine - Ambulatory Project Description: The major objective is to develop better methods of clinical data processing in order to increase the precision of under- standing of patterns and determinants of disease and to direct this information toward the improvement of patient care and student teaching. Name: Cavalli-Sforza, L. Project: PAVIA Department: Genetics Project Description: Programs on storage were mostly developed for simulation of population genetics studies. One of them was developed for the I.C.R.O. course, and is still being used for research purposes. It deals with genetic drift in a human population and takes care of the effects of age structure. Another simulates nutrition, drift, and selection in a haploid population or in a diploid population with additive selection. Others simulate the propagation of hemoglobin mutants in Africa. I will have to use these programs in the coming year, but it is difficult at present to estimate actual use. I am also planning to use ACME for a course for medical students, to teach computer use in simulation experiments that may illustrate the meaning of major statistical methods and some special use of statistics in medical research. 83 Grant No. RROOZ11-04 Section IV Name: Smallwood, R. Project: MEDIPLAN Department: Medical Facilities Planning Project Description: The Stanford Medical Facilities Planning Project was a two-year project that developed several analytical tools for aiding the design of medical facilities. This project synthesized several techniques for analyzing alternative designs for medical facilities both at the indi- vidual nursing unit level and at the overall macroscopic level. All of these tools required computational facilities for their implementation. Each of them resulted in several computer programs, all of which were programmed in ACME PL/1 and used the ACME system for debugging and development. The Stanford Medical Facilities Planning Project was completed in June 1969 and a final report describing the results of this study has been submitted to the Commonwealth Fund. However, at the completion of the project there still remained several unanswered questions concerning the implementaion of the tools that were developed. Thus, an additional block of ACME service was allocated for testing some of the tools on a more expanded data base. This analysis has now been completed and a paper is in preparation that will describe the results of this work. In addition, a proposal for a demonstration project has been submitted which will, if funded, demonstrate the applicability of the results of this project on real design decisions faced by the Stanford University Hospital. Name: Smith, P. Project: ventl Department: . Anesthesia Project Description: This project is to find out if any parameter of mechan- ical ventilation (rate, pressure vt, i.e., ratio) influences paO, in newborn infants with respiratory failure. So far ACME has been tised to store the measured variables and perform statistical maneuvers such as correlation coefficient calculations. A program for estimation of venous lung shunt is included. 8h Grant No. RROO411-oh Section IV Name: Solomon, G. Project: STRESS Department: Psychiatry Project Description: Concerned with the relationship of various forms cf stress and environmental manipulation to immunity. The "STRESS" pro- gram is one that evaluates the significance of differences in antibody titers among control and experimental groups using a Kruskal-Wallis test of rank ordering of serial dilution tube numbers. This program is applicable to all of our work that involves antibody titrations by serial dilution, and is particularly useful for the immobilization assay of anti-flagellar antibody. Name: Stuedeman, D. Project: ADMIN Department: Genetics Project Description: I keep an inventory of IRL capital equipment, update it occasionally, use the computer to locate items, sort by room, or whatever is required. It can be used for preparing reports to sponsors and pre- forming listings in various forms. T also apply the ACME system on various mathematical calculations used in my work, including a study of the University's retirement insurance program. Name: Weissman, I. Project: THYMUS Department: Pathology Project Description: Our use of ACME has been limited to developing methods of applying statistical subroutines to our particular data needs. This has proved most valuable in handling volumes of data which required statistical analysis. For example, in the past year we have modified the chisquare and bastat subroutines to be able to compare 6 standard bits of data with up to 200 test items, giving the exact (p) values of each item. We have also studied the feasibility of setting up a program to analyze raw liquid scintillation spectrometry data from tissue samples, requiring analysis of 3 channels counting simultaneously within different "windows". Channels-ratios must then be obtained and compared to a plot of counting efficiency vs. channels ration, in order to obtain the actual disintegrations/minute/sample. Specific activities and fractional input activities must then be calculated, subtracting physical background counts (solution, bottles, filters) and control organ background counts. Until such programs are developed, and interfaced between ACME and our scintillation counters, we cannot properly study quantitive aspects of in vivo cellular migration streams in the lymphoid system. 85 Grant No. RROO411-04 Section IV Name: Whitcher, C. Project: ONCALLA Department: Anesthesia Project Description: Computerization of the anesthesia call schedule is necessary because the present manual method has proved unsatisfactory. Scheduling is complex, excessive errors have occurred despite due care, and the time required to write schedules is costly in terms of profess- ional and secretarial time. The anesthesia consultant staff includes 1 to 43 research fellows, and 12 to 14 full-time faculty physicians. Duties, responsibilities, and needs of these 13 to 17 individuals are diverse, including teaching, research, further training, as well as the administration of operating room, obstetrical and other forms of clinical anesthesia. Night, week ends, and holiday coverage must be scheduled to cover the various anesthetizing locations as well as vacations, sickness, and out-of-town meetings. Schedules are regularly prepared at monthly intervals. However, changes of plans frequently occur, calling for schedule revision, at additional expenditure of staff and secretarial effort. At least 10 different types of night call work have to be tallied and evenly divided. The computer program already worked out offers several advantages. A running tally is accurate and immediately available. Schedule revisions required by the staff will be rapidly available and will require a mini- mum amount of professional and secretarial staff time. Finally, the estimated savings in staff time should be noted: 12 hours per month secretarial and an equal amount of anesthetist's time which could be more profitably spent in other duties such as income-producing clinical work. Name: Zackheim, H. Project: PSORIAST Department: Dermatology Project Description: The present study is a determination of serum copper and ceruloplasmin levels in patients with psoriasis as compared to other skin diseases and healthy controls. I anticipate at least 60 determinations. I will want the mean, range, and standard deviation on this data. 86 Grant No, RROO41L1-0% Section IV Category 4 Name: Brast, N. Project: CATALOG Department: Medical Student Project Description: The two program files and two data files in this project are an experiment to develop a simple, efficient, and inexpensive arrange- ment for storing and searching bibliographic information, e.g., items in a reprint collection or references for a library research paper. TI have used this project in connection with a paper for Physiology 150 and a laboratory project for Biochemistry 102. During the next six months I shall attempt to complete development of the programs and, if they prove useful, submit them to ACME for inclusion in the Public Program Library. Name: Brast, N. Project: RODENTS Department: Medical Student Project Description: This file contains programs which I have written for calculating descriptive and inferential statistics (e.g., t-test, analysis of variance, regression analysis) on experimental data. One of these programs, ANOVATWO (two-way analysis of variance, unequal numbers of data per cell) has been added to the ACME Public Program Library. In the next six months I anticipate using this file for my own use in con- nection with course work in the Medical School. Grant No. RROO%11-04 Section IV Name: Britt, R. Project: STARR Department: Medical Student Project Description: These experiments will examine auditory pathway responses to meaningful acoustic stimuli. It is a common sense experience that the perception of sound is not determined simply by the physical parameters of the stimulus (intensity, spectral content), but that factors relating to attention, significance, and past experience also play important roles. An electrophysiclogical equivalent of the changing character of perception may be the dynamic alteration of evoked responses to unchanging sound stimuli recorded in auditory pathway of unanesthetized animals. These response modifications are due to activity in regulatory systems including the middle ear muscles, the olivo-cochlear bundle, and descending auditory connections. The specific experiments to be carried out are: (1) an analysis of single unit discharge patterns in central auditory stations in cats making an acoustic discrimination; (2) the effects of olivo-cochlear bundle activity on single unit discharge characteristics in central auditory pathway; and (3) the neural response pattern in auditory cortex of squirrel monkey in response to natural vocalizations. An analysis of how auditory unit discharges in response to meaningful acoustic stimuli differ from their response patterns to non-meaningful stimuli should extend our understanding of the role of the regulatory mechanisms in sound perception. 8& Grant No. RROO311-04 Section IV Name: Brody, W. Project: DIAGNOST Department: Medical Student Project Description: Desire to use ACME to assist medical students with learning the process of history-talking and formulation of differential diagnosis. Case histories will be entered into the computer and students will interrogate the computer to simulate an actual history-talking session. Name: Brody, W. Project: FLYHIGH Department: Medical Student Project Description: I am using ACME to perform calculations of simple simulations of non-linear models of information processing in sensory systems. Name: Brown, B. N. Project: PROTEIN Department: Medical Student Project Description: Studies involve numerous assay data which must be summarized and analyzed. Also, studies of serum levels of therapeutic agents require correlations with age, body weight, suface area, etc. In addition, a study is being made of pharmacotherapy in a group of 900 hospitalized pediatric patients. Biographical and medical data for each patient are stored in the ACME data files, Characteristics of the population and the nature of the drug usage are being analyzed. 89 Grant No. RROO311-04 Section IV Name: Buchanan, B, Project: STAT Department: Medical Student Project Description: This project is a renewal of the education experiment, begun in the Spring of 1969, whose purpose is to determine whether medical students can learn statistical concepts by computer simulation. The emphasis of the course is on using ACME to demonstrate the properties of various statistics and statistical tests. Name: Buchanan, B. Project: GEN217 Department: Medical Student Project Description: This project is a renewal of the education experiment, begun in the Spring of 1969, whose purpose is to determine whether medical students can learn statistical concepts by computer simulation. The emphasis of the course is on using ACME to demonstrate the properties of various statistics and statistical tests. Name: Buchholz, W. Project: SPIN Department: Medical Student Project Deseription: Investigation of time perspective, temporal relation- ships, and social functions in para and quadraplegics. 90 Name: Grant No. RROO311-04 Section IV Calvert, J. Project: TEXT Department: Medical Student Project Description: Mathematical models, e.g.: 1) 2) Allocation of public funds with multiple objective and decision rules, especially with respect to Health, Education, and Welfare. Modified epidemic equations as predicting the interactions of populations of neurons, with goals toward predicting evoked po- tentials with simple stimuli. Allocation rules in health expenditures; by disease, when given incidence rates, probabilities of successful recovery with present treatments, direct and indirect costs per case, and average duration and mortality data. 91 Grant No. RROO311-04 Section IV Name: Edwards, D. Project: STRESS Department; Medical Student Project Description: Using ACME to conduct research on the effects of hor- mones on the alpha rhythm and temporal perception. Data relevant to these experiments are reduced statistically using ACME. In addition, specific programs are used to: 1) generate time intervals to minimize search time for the two-flash threshold, 2) to convert evoked potential amplitude measurements into micro volts, 3) to identify the two-flash threshold on the basis of a linearization assumption, and 4) to prepare and justify manuscripts. In the near future, specific programs will be employed (with the 1800) to identify hormone-induced changes in the EEG on the basis of Fourier and spectical analysis of recorded EFG's. Name: Enzmann, D. Project: SWALLOW Department: Medical Student Project Description: The ACME computer is being used to assist in the study of both normal and abnormal motions of the human esophagus during normal and induced swallowing. A series of simultaneous pressure readings in various locations in the esophagus are taken by the use of water filled manometers connected to electrical pressure transducers. The electrical voltages representing the pressure data are sampled and converted to digital values 5 times a second, for each of the pressure measurement sources, using the IBM 1800 computer attached to the ACME computer system. We plan to have the ACME computer analyze the data from a swallow as it is obtained and provide immediate information back to the experimenter, via the terminal, of the properties of the last swallow. Various summary tables are kept during an experimental run regarding the properties of all the swallows obtained so far, and are available for a final swmary of the experimental data. Initially all the data obtained during an experimental run will be saved on the ACME data files to allow different methods of analysis of the data to be explored. Grant No. RROO311-0} Section IV Name: Gamel, J. Project: DOGLAB Department: Medical Student Project Description: One of the parameters to be derived from indicator dilution measurements of pulmonary blood flow is the "impulse response", which is essentially the distribution of transit times of particles through the lungs. If Ci(t) represents the dye concentrations in the right heart following injection of a bolus of dye at t=O and Co(t) represents the concentration in the left heart, then the impulse response h(t) is described by the equation: s=t Co(t) + § h(s)ci(t-s)ds =0 Replacing the integral with a summation over equally spaced intervals of time: Co(n) = Yh( 4) C4 (0-4) i=0 Thus a program can be written for a digital computer which solves for the function h(t) when given the values for Ci(t) and Co(t). However, a simple staightforward solution yields an impulse response which is hopelessly disrupted by artifacts in the collected data. A technique must be employed which somehow filters the data. Several possible methods are known; one has in fact been successfully used. The program was executed on the Burroughs 5500, a machine which has twelve significant figures in regular precision and twenty-four with double precision. A similar program attempted on ACME accumulated so much error during execution that it proved useless. Thus if we are to achieve our goal using ACME, we must somehow obtain greater precision than is now available. Our current efforts are directed at this problem of insufficient precision. 93 Grant No. RROO311-04 Section IV Name: Gelfand, M. Project: CARCAT Department: Medical Student Project Description: Project "carcat" analyzes cardiac catheterization pressure tracings in children. From catheters in the right and left heart, pressure tracings to determine atrial, ventricular, arterial, venous and wedge pressures. Currently the values in millimeter of mercury are calculated for the a and u waves, x and y troughs, and mean pressures in the artia and great veins, for systolic and end- diastolic pressures in the ventricles, for systolic, diastolic and mean pressures in the great arteries, and for mean pressures for the wedge positions. These values are calculated immediately and printed out on the computer terminal in the catheterization room. At this time, efforts are under way to improve and ascertain the accuracy of the algorithms used in pattern recognition for atrial and ventricular pressure tracings. The basic data acquisition and analysis system that has been set up will also be used to store data acquisition and the analysis system that has been set up will also be used to store data for additional calcu- lations and for the preparation of reports. As data is accumulated in storage from cardiac catheterizations and from other sources of clinical information, it will be possible to analyze rapidly large amounts of clinical data using the ACME computer. Research into methods of storing and recalling data for analysis of clinical information will be an important part of our future efforts. Grant No. RROO311-o04 Section IV Name: Gleason, C. Project: CORTMEAS Department: Medical Student Project Description: I have been using ACME primarily in an educational way to learn how computers can be used in electro-physiological research. Name: Hahn, P. Project: OXYTOX Department: Medical Student Project Description: This project is concerned with the interpretation, quantification, and systematic retrieval of information from gel electrophoreses. In our laboratory, we are looking only at proteins separated by electrophoresis on acrylamide gels. Since it is very difficult to get clean backgrounds for the electrophoresis columns, it is highly desirable to have a computational program capable of analyzing multiple overlapping bands, correcting the peak positions and integrated areas of these bands to their appropriate baseline positions, and storing the information in a useful form. Grant No. RROO411-04 Section IV Name: Harris, R. Project: PNP Department: Medical Student Project Description: Our project is an attempt to demonstrate correlations between the emotions experienced by subjects and their own appraisals of certain aspects of their enviromments. Our concept is that emotions arise when events in the individual's situation come into certain specified relations with his goals. For example, if an individual perceives such events as facilitating rather than hindering his potential achievement of the goal, then he will experience a positive emotion rather than a negative one, Similarly, other dimensions, such as the extent to which the individual feels in control of the situation, the extent to which he is explicitly pursuing a goal within the situation, and the degree of certainty with which events in the situation affect his potential achievement of the goal, are also hypothe- sized to be important in determining which of a number of different emotions the individual will experience in any situation. The emotional state consequent to such appraisals is thought to have physical and cognitive effects specific to it. Cognitive effects inelude changes in the perception of time. For example, different emotional states may be associated with different focus of attention with respect to past, present, or future events in the life of the individual. By physical effects we mean the individual's sensations of changes occurring within his body as part of the emotional state. We are developing standard inventories for obtaining objective measures of these subjective variables. The study will have two parts. The first involves the collection of normative data from normal subjects with respect to six emotions; namely, anger, anxiety, depression, joy, love, and calm. Subjects will be instructed to recall experiences that typify their conception of these states and to describe them on our inventories. We will use this data to construct normative profiles of each emotional state and to calculate correlations between different eategories of items on our inventories. The second part of the study will employ a number of expectant fathers, who will be tested in the waiting room prior to delivery and again after the birth. This data will be used to determine whether our previous normative data is useful in the identification of actual emotional states and to confirm the correlations fcund in the earlier part of the study. We plan to collect the data for the first part of the project by the end of February and to process the data at that time. Data from the second part of the study will be collected by the end of April and processed then. If successful, the study could have important theoretical and methodological implications. Theoretically, we hope to demonstrate that an individual's subjective appraisal of events in relation to his goals are important determin- ants of his emotional state. Methodologically, we hope to show that certain forms of inventories yield replicable descriptions of subjective events. Normative profiles such as I have mentioned could thus be constructed and employed as operational definitions of emotional states in a number of experi- mental contexts. Studies in the physiological correlates of emotions are but one class of examples. 96 Grant Ne. RROO311-04 Section IV Name: Helikson, M. Project: LBF Department: Medical Student Project Description: Evaluation of liver blood flow with radioactive isotopes. Use of the ACME Facility: storage of data, statistical analysis, and evaluation of curves into exponential components. We are using radioactive Xenon-133 to evaluate the hepatic-arterial and portal-venous contributions to hepatic blood flow in dogs. It is our objective to develop a relatively quick and technically easy method for determining blood flow in humans on a screening basis and in pathologic states. Name: Jan, W. Project: NOMAN Department, Medical Student Project Description: Processing, storage, display, and statistical analysis of laboratory data and text editing; development of programs to aid decision making; and information storage, retrieval, and display. Name: Levine, R. Project: CPS Department: Medical Student Project Description: The purpose of the initial investigations is to isolate and purify the carbamyl phosphate synthetase involved in fetal pyrimidine synthesis. This enzyme is apparently distinct from that providing car- bamyl phosphate for the urea cycle, whose enzymatic activities appear later in gestation than the de novo pyrimidine activities, The major work thus far has been on development of a rapid simple assay for the enzyme. My primary use of ACME has been to evaluate and process data obtained during assays. There is no question that without ACME's assistance, the already burdensome assay work would become intolerable, It is expected that as work with the purification progresses, we will examine possible regulatory and control mechanisms in which this enzyme may be important. Grant No. RROO311-04 Section TV Name: Lipp, M. Project: MEDSPOT Department: Medical Student Project Description: Survey medical students and graduate physicians regard- ing their experience with and opinions of marihuana. We intend to dis- tribute questionnaires to medical students at several medical schools (Stanford, Nebraska, Buffalo, and perhaps others), disguising the speci- fie origins of each set of data in any published report. We wiil then expand our distribution of questionnaires to graduate physicians. All responses will be strictly voluntary and ananymous. Name: Miller, §, Project: LEARN Department: Medical Student Project Description: Analysis of data from an ANGER scintillation camera in connection with kidney blood flow studies. Name: Monnin, L. Project: DISCRIM Department: Speech and Hearing Sciences Project Description: A study of the relationship of articulation and identi- fication abilities of normal speaking and speech defective children. Distorted speech stimuli will be presented to the subjects so that an identification threshold can be estimated. 98 Grant No. RROOS11-04 Section IV Name: Nestor, L. Project: DIFFDX Department: Medical Student Project Description: In medicine, many diagnoses are missed merely because certain disease entities are overlooked as possible causes of the ob- served symptoms. This project will be used to develop a system, which can be easily adapted to general practice, which will bring to the doctor's attention diseases which he may not have considered in his differential diagnosis. Name: Nola, G. Project: DIGMI Department: Medical Student Project Description: This project will serve to perform statistical analysis of hemodynamic parameters, i.e., right atrial pressure, left atrial pres- sure, aortic pressure, left ventricular systolic pressure, left ventricular dp/ dt, aortic flow, and EKG. The analysis would include mean, standard error, I change, correlation, and paired and unpaired +- test for permanently entered data, Name: Nowack, W. Project: CATECHOL Department: Medical Student Project Description: Computer analysis and simulation of the metabolism of catecholamines in the rat, The changes in different rate con- stants offer different behavioral situations. Also drug treatments will be studied. 99 Grant No. RROO311-04 Section IV Name: Peters, J. Project: BIOSTAT Department: Medical Student Project Description: Conducting statistical research in the area of evalua- tion of residuals and outliers in parallel line assays. Name: Pope, S. Project: AY21011 Department: Medical Student Project Description: Statistical analysis of data sets of cardiovascular function parameters of various pharmaecologic agents. Name: Portlock, C, Project: PAUP Department: Medical Student Project Description: The study involves developing some knowledge to under-~ stand the motivations for pregnancy. A great deal of quantitative in- formation is obtained from the patient through questionnaires and through rating by observers of interview behavior. This quantified data is then transformed into a form that can be used for computer analysis. The computer will be used to do a number of types of analyses, i.e. an analysis of the answering patterns of 80 subjects on a recently developed questionnaire, LOO Grant No. RROO311-04 Section IV Name: Propper, R. Project: TEST1 Department: Medical Student Project Description: This project will involve the study of inter-relation- ship of annogenesis glucomedgenesis in the perfused kidney, Name: Raybin, D. Project: ASSAYS Department: Medical Student Project Description: Write, store, and run programs: 1) to calculate results of assays and 2) to handle other data calculations, statistics, ete. Eventually, write up results using text handling programs. Name: Rosenfeld, R. Project: CCUPSYCA Department: Medical Student Project Description: Studying the psychophysiological adaptation of male patients to the Coronary Care Unit. The goals of the research are to try to establish some relationships between psychological variables and physiological variables, particularly as these latter affect the mor- bidity and mortality of patients with acute myocardial infarctions. The patients on the Coronary Care Unit are under constant daily obser- vation and have a large number of physiological funetions monitored, The study will provide a huge amount of data daily on each patient. The ACME computer will be used to store this data and make a number of statistical manipulations of the data. Name: Rosenthal, W. Project: RESEARCH Department: Medical Student Project Description: I am using the computer essentially for statistical analysis of data in connection with various experimental studies in speech and language pathology and normal speech perception. These studies include research in effectiveness of stuttering therapy, speech and auditory perception in aphasic children, and normal speech perception in adults and children. 101 Grant No. RROO311-04 Section IV Name: Sachs, D. Project: POPCIT Department: Medical Student Project Description: ACME will be used as a text editing system for a manu- script which is being prepared dealing with various aspects of environ- mental medicine and the population explosion. ACME will also be used to study population growth rates in various nations, correlate these with natural resource use, and then calculate projections for the next 10, 20, 30, 40 year periods. Name: Schwartz, B. Project: CELLSAGE Department: Medical Student Project Description: 1) Statistical modeling of the growth, development, and ultimate senescence of cultured human fibroblasts. Special attention will be paid to the possibility that the in vitro senescence of tissue culture cells might parallel age-related degenerative changes found in the intact organism. Variation analyses. will be performed on clones of cells. It appears that clone size variation may be accounted for by two processes: a) an exponential, randomly distributed interdivision time and b) a probability of cell mortality, possibility related to time in culture or passage level, which may also be amenable to statistical simulation. 2) The storage, sorting, logical processing, and retrieval of data and observations related to cellular aging. As the amount of descriptive work done in this area explosively increases, it might be helpful to be able. to instantly access all the published data dealing with the effects of age on some specific cellular function. Also, in addition to its information retrieval aspects, a routine in the program might be designed to seek logical relationships among the data that might other- wise have been obscured by the diversity and large quantity of the infor- mation to be considered. Loe Grant No. RROO411-0% Seetion IV Name: Sethi, S. Project: ISOTOPE Department: Medical Student Project Description: Analyzing the data from experiments being conducted to understand the replication of rhinoviruses. The data involves the calculations and plotting of data from the experiments which involve the radioisotopic counts in the lucrose gradient factions of RNA. Also, the data will be used to calculate the significance of results with respect to plaque assay of virus. Name; Sinclair, A. Project: HEARTCEL Department: Medical Student Project Description: Pharmacological studies using cultured chick embryo cells. We have devised a system using television and subsequent photo- electric monitoring arrangements to record the beat time intervals and motion spike signals of individual cells in culture. We subject the cells to various dosage regimens of neuro- and cardio-active drugs and note the effects on rate, rhythmicity, and other parameters. At this stage, the primary data are the beat intervals. From these in- tervals (nm specific time intervals after drug administration) we will need to compute average intervals, rates, standard deviations and errors of mean, and Spearman Rank Correlation Coefficients. After computing these parameters we will need drug/ control ratios, t-test- ing, u-testing, and other comparative statistics. Name: Smith, R. Project: FAMILY Department: Medical Student Project Description: The ACME system has been used to store analysis data from an experimental study of family structure which I conducted during the past year. The project contains one data file (SDM) and a number of program files to analyze the data. Most of the analysis has been completed during the past year, but some still remains to be done. JI have also done some socio-physiological studies of kidney transplant patients, data which T will be entering in the near future. I plan to make intermittent use of ACME for further analysis of data from these projects during the next six months. LOZ Grant No. RROO311-o04 Section IV Name: Swanson, G. Project: THESIS Department: Medical Student Project Description: Our long term goal is to interpret therapeutic drug action on respiratory control. The objective of my thesis is to develop a quantitative description (model) to characterize brain and CO,, chemoreceptor dynamics. We have implemented a system in which voluntary effort, inspired CO, concentration and, indirectly, alveolar CO,, concentration can easily fe controlled, The data obtained (in- spired CO, concentration, alveolar CO, concentration, alveolar ventila- tion, tidal volume, exhale time, inhale time, and breathing frequency) will be analyzed and used to develop a model. Modeling will be done on a hybrid system using ACME and the Department of Anesthesia's analog computer. The experimental techniques are new because previous CO response experiments have been done with step changes in inspired CO, and re- breathing. Since we can force CO, concentrations to follow“a pre- determined time function, we hope to answer questions relating to chemoreceptor rate sensitivity and the role of peripheral chemorecep- tors. Modern control theory will be applied to determine optimum res- piratory center dynamics with respect to regulation of cerebrospinal fluid pH. 104 Grant No. RROO411-0} Section IV Category 5 Name: Bellville, J. Project: PROBABIL Department: Anesthesia Project Description: This study is of the pharmacology of anesthetics and related agents. Statistical programs are stored in the 360/50, so that with the 2741 terminal on cue, the data are entered. Various procedures are carried out. For instance, the relative potency of a biologic com- pound and its associated 95% confidence limits are computed. lambda, a measure of efficiency of the assay, is also computed. Standard sta- tistical procedures are stored under this project, and carried out by research fellows or the principal investigator. Name: Bellville, J. Project: GAS MASK Department: Anesthesia Project Description: This project involves the use of a special purpose analog computer that preprocesses data, which is then entered into the 360/50 via the 1800. In addition, the 1800 interacts with the experiment to generate sinusoidally varying carbon dioxide which is administered to the subject. Thus, we are doing research not only on the basic physiologic mechanisms involved with the control of respiration, but on the use of digital compu- ters on-line in the control of experiments in the acceptance of data from special purpose analog computers and the storage, analysis, retrieval, and display of these data. This represents an entirely new approach to the study of respiratory control mechanisms, and could not be carried out without the ACME Facility. 105 Grant No. RROO411-04 Section IV Name: Bunnenberg, E. Project: CHEM Department; Chemistry Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experimental analysis programs so as to develop programs for the routine analysis and finished output of mass spectra. The trans- mission is through the 270X-270Y channel. The project plans to develop this interface to service two mass spectrometers (ALTAS CH and AEIT MS9). The taken spectra are then to be fed to the Artificial Intelligence group under the supervision of Joshua Lederberg and Edward Feigenbaum to be used in their investigations. (B) Another use of data transmission through the 270Y is to take spectropolorimeter measurements and then analyze these spectra for form, bandwidths, and Similarities between derivatives for theoretical projections. (C) The project mentioned also includes a battery of utility programs for metastable analysis, chemical rate analysis, C13 substitution ratios, and other routine analyses that the chemists wished programmed. Name: Bunnenberg, EF, Project: JAY Department: Chemistry Project Description: Same project description as for project CHEM. Name: Bunnenberg, E, Project: MASSPEC Department: Chemistry Project Description: Same project description as for project CHEM. 106 Grant No. RROO311-04 Section IV Name: Bunnenberg, E. Project: PEACE Department: Chemistry Project Description: Same project description as for project CHEM. Name: Duffield, A. Project: DRONGO Department: Chemistry Project Description: The ACME computer system will be utilized for rapid accumulation of high resolution mass spectra. The necessary peripheral equipment to accomplish this has been assembled and the complete system shown to yield data. These spectra will be obtained from organic com- pounds; many of them of biological significance. The fast acquisition of high resolution data will enable organic chemists to solve problems related to their research more quickly. Name: Glick, D. Project: LASER Department: Pathology Project Description: The ACME Facility is needed to provide the computational requirements of the laser microprobe analytical system which we have designed, and are continuing to develop, for elemental analysis of micro- scopic biological samples down to the single cell and very small volumes of fluids. The applications of the system to biological and medical research and clinical medicine obviously have impressive potential. ACME is involved in data calculation for definition of sample size as well as content and concentration of elements. Statistical evaluations include calculation of F-ratio, T-test, U-test, population means and and also linear regressions, graphical interpolations and curve fitting. A second system has been built so that one can be devoted to applications and the other to continued technological development. This will, of course, at least double our need for use of ACME. Eventually we expect to automate the system, which would further increase our dependence on ACME. Loy Grant No, RROO311-04 section IV Name: Roth, W. Project: COMP Department: Psychiatry Project Description: This project involves computer analysis of habituation of the evoked response and EEG desynchronization. Also an attempt will be made to distinguish states of arousal produced by emotional stimuli. Analysis methods include spectral density calculations based on the "fast" Fourier transform, period analysis (Burch), and response averag- ing to improve the signal-to-noise ratio. Name: Stillman, R. A. Project: DRAFT Department: Chemistry Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experimental analysis programs so as to develop programs for the routine analysis and finished output of mass spectra. The trans- mission is through the 270Y-270X channel. The project plans to develop this interface to service two mass spectrometers (ALTAS CH4 and AET MS9). The taken spectra are then to be fed to the Artificial Intelligence group under the supervision of Joshua Lederberg and Edward Feigenbaum to be used in their investigations. (B) Another use of data transmission through the 270Y is to take spectropolorimeter measurements and then analyze these spectra for form, bandwidths, and similarities between derivatives for theoretical projections. (C) The project mentioned also includes a battery of utility programs for metastable analysis, chemical rate analysis, C13 substitution ratios, and other routine analyses that the chemists wished programmed. Name: Trudelli, J. Project: MASS SPE Department: Chemistry Project Description: I am working on computerized interpretation of mass spectroscopy. At present, information is visually taken from strip chart recordings and entered into the computer through a keyboard terminal. The computer then assimilates the data and presents the results in tabular form. In the near future the data will be acquired on-line using the 270X-Y system. 108 Grant No. RROO311-04 Section IV Category 6 Name: Bernfield, M. Project: TRNA Department: Pediatrics Project Description: The ACME system is used by our lab to handle two tasks that would ordinarily take many hours of routine effort. (1) The program we have written takes the radioactivity found as aminoacyl tRNA at several points in time and computes the least square best fit to the log of the radioactivity left, and also gives the rate constant for the decay and the half time. (2) Some column and paper separation techniques used in our lab involve over 100 fractions, each double labelled. The program for this task takes the data generated by the scintillation counter and subtracts background and interference (cross talk) between the two isotopes. This data is then presented in graphic and tabular form as percent of the respective isotope by fraction number. Name: Cann, H. Project: GUAT Department: Pediatrics Project Description: Same project description as for project DTS. LOO Grant No. RROO311-04 Section IV Name: Cann, H. Project: DTS Department: Pediatrics Project Description: This research project is investigating factors which affect frequencies of genes controlling various human heritable char- acters, The extent to which selection, genetic drift, and migration affect frequencies of certain human genes is being assessed and specific selective factors are being sought. Environmental, cultural, and his- torical conditions favorable for this type of study have been found in settlements of Mayan Indian descendents in the Lake Atitlan Basin of southwest Guatemala, The local microgeography and mating patterns ap- pear to enforce a high degree of genetic isolation for each of a num- ber of Indian towns and villages ringing Lake Atitlan. These high mortality populations provide the opportunity to study selective ef- fects of human genetic polymorphisms. Studies of gene frequencies, segregation analysis of polymorphisms and demographic characterization of these sub-populations are being undertaken. This project will also contribute information on the genetic taxonomy of the American Indian. Families of large size, characteristic of the study population, will afford excellent opportunities for medical gene- tic investigation of inherited diseases encountered in our field activi- ties and for studies of genetic linkage. Two communities on the east shore of the lake are being studied and we are about to initiate studies in another Indian lake shore community. A pilot project involving 300 inhabitants of two Indian communities on the south shore of the lake was completed prior to undertaking the present investigation. LLO Grant No. RROO411-04 Section IV Name: Champoux, J. Project: BIOK Department: Biochemistry Project Description: Write programs to do multiple calculations with many sets of data from analytical ultracentrifuge experiments and double label counting experiments. Name: Chase, R. Project: CPGRAC Department: Surgery Project Description: Obtain statistical information from measurements of cephalometric film. This information is to be used to evaluate facial growth in cleft palate children and to assess velopharyngeal competence, Name: Clayton, R. Project: SEXBRAIN Department: Psychiatry Project Description: The purpose of our project is to determine the effects of steroids and hormones of RNA activity on the brain. We inject live vats with radioactive tritriated uridine. The rats are then killed and processed in the regular histological procedure. Radioactive element reduces silver grains and slides are made from which the grains in the brain cell are counted. From the number of grains, we determine the area of RNA incorporation in the brain, the brain cell, and other tissues. The level of RNA incorporation is also determined. Experimental and control groups are compared by ACME. Our data analysis time is greatly reduced by using ACME. lil Grant No. RROO411-04 Section IV Name: Cooper, J. Project: SEXDIFF Department: Psychiatry Project Description: At present I am using ACME for two purposes: 1) com- parison of 2 sets of data by means of the t-test and 2) calculation of sample radioactivity together with standard deviation thereof. [I do not envisage expansion of this work. My project lies essentially in investigation of biochemical correlates of neonatal sercual differentiation in rats: such as androgen metabolism. Name: Doering, C, Project: DESMOLAS Department: Psychiatry Project Description: In a mammalian system, one of the responses to a stress is the secretion of certain steroid hormones by the adrenal gland. Another response very often is a distinct pattern of behavior. We are investigating the causal connections, on a biochemical level, between hormones and behavior in stress. We use inbred strains of mice that differ in their response to stress in terms of behavior, adrenal hor- mones, and in other biochemical parameters. By genetic analysis cor- relations among these parameters can be tested, ACME is used for a variety of computations in this study. Data from the extensive use of radioactive chemicals have to be converted from the raw output of a liquid-scintillation-counter to their final form, The output. of a gas-liquid-chromatograph has to be compared to a plot de- rived from standards and recalculated to another form. And perhaps most important, all results have to be analyzed statistically. At this time, the computer saves us a great deal of time, Some programs are adapted from earlier work under this project name; some are new. The statistical programs are adapted from ACME's program library. lle Grant No. RROO311-04 Section IV Name: Doherty, R. Project: SEXCHROM Department: Pediatrics Project Description: I am currently using ACME for: 1) statistical evaluation of experimental data, and 2) calculation of random fields to obtain random sampling of cells dispersed on microscope slides. Sex chromatin body counts are being obtained on the random cell sample by visual search. Name: Efron, B. Project: BIOBRAD Department: Community & Preventive Medicine Project Description: Theoretical and applied research in biostatistics. Name: Folk, W. . Project: GRS Department: Biochemistry Project Description: My ACME use will primarily involve the calculation of rough data dealing with work I am doing on mitants of Ecali having altered activating enzymes (amino acyl TRNA synthetases). The calculations will primarily be of an arithmetical nature - taking data from sanhillahran counting and laboratory assays and computing various variables from this data. 113 Grant No. RROO411-04 Section IV Name: Fries, J. Project: DXARTH Department: Medicine - Immunology Project Description: Presenting projects involving computer diagnosis of rheumatic disease are partly designed to increase our familiarity with the ACME system. Beginning in late Spring 1969 we will start work on a large-scale data file entry, storage, and retrieval system for clinical information about rheumatic diseases. This system has exciting pos- sibilities for improving quality of clinical research, quality of medical care, accuracy of diagnosis, extension of the medical school influence into the community, etc. Name: Hahn, G. Project: RADIATE Department: Radiology Project Description: Simulation of time and dose fractionation studies of radiochemotherapy of mammalian cell cultures. Lit Grant Wo. RROO411-04 Section IV Name: Herzenberg, L. Project: LAB Department: Genetics Project Description: Our studies in immunology, genetics and maternal fetal immunologic relationship's in the mouse require the colation of many experimental observations on a given serum sample or individual. Since such data is accumulated over long periods of time, frequent interim reviews must be made to determine new directions, etc. Currently, most data collation in our laboratory is done by hand incompletely, inadequately and infrequently, thus hampering the process of the research. To over- come these difficulties we have begun the process of changing our data storage procedures to utilize the ACME capabilities. For example, all breeding records for the inbred nucleus of our mouse colony are stored in ACME. Approximately onee a month ACME is called upon to draw updated pedigree charges, so that breeding decisions may be made. Presently we are working on programs tocollate multiple immunoglobulin level determinations done on individual serum samples, returning histories of immunoglobulin level changes with time in treated animals. Eventually we hope also to be able to use ACME to store data and direct antiserum production in the laboratory. In addition to the data storage aspects of ACME, the computer is used in this Laboratory for a number of routine calculations on data sets, e.g., per cent antigen precipitated, geometric means of plaque events, etc. Name: Herzenberg, L. Project: PIGGY Department: Genetics Project Description: Same project description as for project LAB. Name: Herzenberg, L. Project: STORE Department: Genetics Project Description: Same project description as for project LAB. 115 Grant No. RROO311-04 Section IV Name: lLaipis, P. Project: LIGASE Department: Genetics Project Description: The computer is being used for statistical and mathe- matical reduction of data from experiments connected with my graduate research, principly those experiments involving sucrose and cesium chloride gradients in the ultracentrifuge. Name: Pearson, M. Project: CTCOR Department: Biochemistry Project Description: The program is used to compute normalized chromatographic elution profiles of viral SRNA. We have found that induction of lysogenic bacteria results in the formation of a set of small molecular weight ordered RNA's coded by phage } DNA. These RNA's have physical character- istics similar to transfer RNA and may be intimately involved in genetic control. The set of viral RNA's can be fractionated on benzoylated deae columns. The computer normalizes the elution profiles of viral RNA's to a constant total output RNA, allowing comparison of the relative amount of each viral RNA from one column run to the next. It is anticipated that future programs will be used to calculate quench- corrected values of radioisotope activity in double-label experiments, using data from a liquid scintillation counter. 116 Grant No. RROO311-04 Section IV Name: Robertson, W. Project: UGAG Department: Pediatrics Project Description: (1) Data on urinary analyses of glycosaminoglycans both on patients and normal individuals will be entered. The curve relating concentrations to age in normal children will be developed. The values of groups of children with different diseases will then be compared with normals to discover which diseases lead to abnormal excretion. (2) Analytical data on immunoglobulin concentrations in sera from patients with a variety of immunologic diseases will be entered and correlations developed with the clinical state of the patient and therapy. (3) Data on the binding of ligands to macromolecules, e.g., cortisol to hyaluronic acid will be used to determine association constants. Name: Saunders, A. Project: MASTCELL Department: Pathology Project Description: Multiple numerical parameters are determined for single cells under varying conditions of staining and animal pre-treatment. Analysis of results lead to conclusions on the type and quantity of poly- anion in the mast cells under study (once thought to be just hepanin). Hence the project involves the chemistry of Hepanin type substances at the single cell level, the maturation and biology of the mast cell in rats and people, and development of methodology, mostly centering on fluoresence microscopy. Name: Saunders, A. Project: SPHERES Department: Pathology Project Description: Cells measured by a rapid sensor system. Data collected on tape and records will be transformed from a LINK to ACME for storage and analysis. 117 Grant No. RROO311-04 Section IV Name: Savageau, M. Project: KINET Department: Cardiology Project Description: I am concerned with the kinetic behavior of systems of enzyme catalyzed reactions. During the coming year I expect to use the ACME computer in three ways. First, I will use it to store and process experimental data from enzyme systems. Second, a nonlinear curve fitting procedure will be implemented to estimate the kinetic parameters for the mechanisms yielding the experimental data. Third, the solution of the system of differential equations will be simulated to obtain the temporal behavior of these enzyme systems. 118 Grant No. RROO411-o4 Section IV Category 10 Name: Butler, E. Project: UROLOGY Department: Urology Project Description: ACME is used to study the dynamics of the urinary tract. The following real-time measurements are made: 1) electromyographs of the ureteral smooth muscle, 2) urine flow rate, and 3) blood pressure/ fluid load/bladder pressure, Macroscopic analysis of these is made at the end of every 30 minute experiment with a graphical output typed out on the 2741 terminal. This provides feedback for the next 30 minute run. 10-15 such runs are made per complete experiment. Microscopic analysis is made of item (1) off-line on the effect of drugs on the waveform which necessitates use of the TV display console, Digital filtering, histogram plotting, averaging, and autocorrelation is performed. Data files are kept of the reduced data points. Several of the standard statistical subroutines are used, e.g., Fourier analysis, spectral analysis, and frequency plots. Name: Constantinou, C. Project: METHODS Department: Urology Project Description: Study the ureteral electrophysiology action potentials as recorded from microelectrodes from the smooth muscle of ureters in anesthetized dogs. The ACME system will be used for analogue to digital conversion and digital to analogue output for an on-line XY plotter, digital filtering, Fourier analysis, and waveform averaging. 119 Grant No. RROO41L1-04 Section IV Name: DeGrazia, J. Project: RADIOGAS Department: Nuclear Medicine Project Description: The project is a pilot study of the clinical or investi- gative potential of a relatively new tool for assessing in vivo human biochemistry. It is based upon the simple assumption that the measure- ment of ~ CO, release into a patient's breath following the administra- tion of appropriately labeled compounds (radiorespirometry) can be of considerable value in assessing the in vivo rate of oxidation of those compounds. Pilot studies of the feasibility of this approach indicate it is possible to study the specific alteration of metabolism associated with a disease state, Such studies have shown that this information is useful both as a means for diagnosis as well as for the evaluation of therapy. The relative simplicity of this technique makes the survey of large patient populations possible. This leads to the accumulation of a large volume of data. We have now begun a pilot project for the com- puter handling of this data and hope to thus speed our calculations as well as to further our understanding of the clinical significance of the kinetic aspect of this data. Although a relatively simple program is adequate for the moment, it is anticipated that with further develop- ment and modification of this technique the complexity of this data handling will increase considerably. It is hoped that a practical clinical demonstration of the coordinated use of the computer for the direct in vivo evaluation of human biochemistry will result from this work and that it will become a routine tool for the determination of the diagnosis or adequacy of the therapy of the patient. Name: MacPherson, L. Project: META Department: Psychiatry Project Description: In this laboratory, studies are in progress on the comparison of EEG responses evoked by visual stimuli incorporating a direction component in dyslexic and normal children. The subjects observe a series of arrows that point either upwards, left, or right. These stimuli last 100 msec and occur every few seconds in random sequence, In each experiment the subject is asked to respond to one of the groups of arrows by pushing a button; measurement of the stimilus- response interval is also under investigation. Project META is now mainly concerned with the provision of programs and operational methods in this laboratory as required by the dyslexia experiments. Many of these methods and programs are also applicable to the AROGUESS project in the same laboratory. 120 Grant No. RROOZ11-04 Section IV Name: Ridges, J. Project: VOLUMES Department: Cardiology Project Description: Analysis of cardiac catheterization data by the computer. One of the projects involves development of a program for analysis of atrial pressure contours. Simultaneous atrial pres- sure and electrocardiogram will be digitized from the cardiac cathet- erization lab and stored. This data will then be analyzed for wave pressure valves and descent rates using the electrocardiogram as a marker for definition of search areas in the pattern recognition. The analysis will be documented using valves obtained by routine hand measurements of the data. A second project involves the analysis of ventricular function during angiographic procedures in the catheterization laboratory. Simultan- eous pressure, syringe excursion, cine-shutter marker and electro- ecardiogram analog signals will be digitized from the laboratory dur- ing dye injection. The digitized volumes, obtained through the Ames Research Center at NASA will be merged with the pressure and ECG data, The merged data will then be analyzed for pressure volume relation- ships in order to evaluate ventricular function. del Grant No. RROO311-o04 Section IV Name: Sanchez, J. Project: RADIOREN Department: Radiology Project Description: Develop radioisotope techniques for the evaluation of differential kidney function, In this project we plan to use a four- probe detector system with analog tape recorder. With this equipment we will compare the excretion and possibly the metabolism of an intra- venously administered isotope by each kidney with the appearance of the isotope in the bladder and with its removal rate from the blood. In phase one of this project a program will be written to calculate the data from the four probes and to record the data upon an X-Y plotter. We will next conduct double isotope studies initially using I-131 hippuran and I-131 albumin. From the data obtained in serial studies with the same patient using these two isotopes a correction for hip- puran distribution and retention in renal blood pools will be made. If successful, this clinically applicable "corrected" radioisotope renogram will be made a standard test for renal function. It is ex- pected that these studies will lead to an improved means for the clinical evaluation of renal function, and it is hoped that they will also serve as a model for other studies with new isotopes, particu- larly those with a very short half-life in the near future. Name: Sherwood, 58. Project: BRAINWAV Department: Neurology Project Description: This project is designed to advance the understanding of electroencephalographic phenomena. It is proposed to obtain records, suitably amplified, on magnetic tape from patients and normal subjects through different electrode arrays and placements and analyze the ratio of amplitude to wave-length of different waveforms. This is intended to be a first step; further mathematical methods are hoped to shed more light on the nature of the EEG in later stages, without interfering with the brain itself. 122 Grant No. RROO411-0) Section IV Name: Sussman, H. Project: LABSYS Department: Pathology Project Description: The purpose of this project is to establish a modern system of handling the data flow in the clinical laboratory. This will be the initial step in a larger program to set up an automated, systems oriented, clinical laboratory center at Stanford University Medical Center. There is an immediate need for improvement in this area at Stanford for the present facil- ities to be capable of meeting the expected, progressive demands for laboratory services. The specific aims of the project are to establish a means for order- ing tests and reporting test results in semi-automated, machine-retrievable way. This will aid in (1) the ability to provide prompt and reliable reporting of data to physicians, (2) will reduce the billing costs which will be of benefit to the Hospital and to the patient, and (3) should increase the effectiveness of using this laboratory's findings in the care of patients with disease and in monitoring the progress of disease in response to therapy. 125 Grant No, RROOZ11-04 Section IV Category 11 Name: Allway, R. Project: FIB Department: Pediatrics Project Description: We have data on various aspects of illness behavior in families collected from 60 families over the past year. Our main aim is to compare various types of information we have on family structure, attitudes, and previous illness histories with symptom data collected monthly from family members over 2-3 month spans of time. We are particularly interested in predicting from both the family as a whole and individual members of the family to general illness symp~ tomatology, frequency, duration of symptoms, and family responses to symptoms. Our computational needs involve some correlational analysis where we have ratio scale data and some analysis of means where we are simply describing categories of persons or families against symp- tom frequency data. Name: Butler, E. Project: UROSTATS Department: Urology Project Description: The Residency Review Committee of the American Medical Association has imposed increasingly detailed statistical records of residency training programs as a requirement for continuing accredita- tion. The Division of Urology maintains residency training affiliations at five major hospitals. The statistical burden has become so great during the past year that we have undertaken the development of a com- puter based system of information collection storage, and retrieval. If we can demonstrate a real usefulness of computers in the sphere of medical education then the potential for development of such programs on a wider scale appears unlimited. 124 Grant No. RROOS11-04 Section IV Name: Doering, C. Project: INDEXV15 Department: Psychiatry Project Description: A comprehensive author and subject index is to be prepared for a 700-page (approximately) volume, Methods of Enzymology, Sterols and Steroids, Volume XV, edited by Dr. R. B. Clayton and to be published by Academic Press. ACME is to be used to store all entries with page numbers. ACME can then produce a listing of all entries in alphabetical order. Name: Enlander, D. Project: cases Department: Pathology Project Description: I am endeavoring to devise a system whereby medical diagnoses can be filed in disc storage in coded form. The coding is automatically derived from a thesaurus file by matching key words, which will conserve both file space and enable synonymous diagnoses to be retrieved efficiently. The basic thesaurus and code is based on the common S.N.O.P. (Standard Nomenclature of Pathology) on account of its wide usage and comprehensive modern terminology. Name: Enlander, D. Project: snop Department: Pathology Project Description: Same project description as for project cases. 125 Grant No. RROO311-04 Seetion IV Name: Enlander, D. Project: PIPIC Department: Pathology Project Description: Same project description as for project cases. Name: Friedland, G. Project: SLING FI Department: Radiology Project Description: Determine the function of the gastric sling fibers, The gastric sling fibers are a muscle band lying internal to the other muscle layers, which hook around the notch between distal esophagus and gastric fundus and then traverse the stomach anteriorly and posteriorly parallel to the lesser curvature. Feline sling fibers have been marked by insert- ing tantalum wire strips into them through a needle. Simultaneous bi- plane radiographs have been exposed at 1 frame/ second for 1 minute before, during and following deglutition. The purpose of this approach is to in- vestigate the possibility of extracting quantitative information by measur- ing the marker's position on the films. The measurement of the relative position of the markers in each plane is added vectorially utilizing the computer. A spatial representation of these points is projected on the digital television screen, frame by frame, in the same sequence as the roentgenograms. Measurements are then abstracted from the digital tele- vision and stored into data files. This information is to be utilized to determine the applicability of this method to conduct meaningful experiments employing our present roentgenographic framing rate, 126 Grant No. RROO311-04 Section TV Name: Henry, P. Project: SLEEP Department: Psychiatry Project Description: Develope routines for processing hand staged sleep and wakefulness EEG data printing out summary statistics and graphics. Also, develop and test programs for the automatic staging of sleep EEG data and develop pattern recognition subroutines to identify and count monophasic sharp waves recorded from the lateral geniculate during sleep. Name: Hillman, R, Project: THERAPY Department: Psychiatry Project Description: Study to construct computerized psychiatric "patient." Ultimately aim at a teaching and research device capable of appropri- ately responding to therapist's comments. Computer will respond to limited types of responses (modifying statements, interpretations, etc.) with random comments (resistance, denial, insight, ete.). Built into the system will be: 1) teaching comments, 2) statistical analysis of "routes" taken, 3) ability to retreat to a prior stage in the interview and take a different course, and 4) positive and negative correlation between the therapist's comment and the computer's response. Advan- tages of the program are: 1) reproducible data, 2) availability of specific diagnostic entity, and 3) learning to do interviews without traumatizing real patients. ley Grant No. RROO311-04 Section IV Name: Korn, D,. Project: SNOP Department: Pathology Project Description: The endeavor is to devise a system whereby diagnoses can be filed in dise storage in coded form. The coding is automatically derived from an internal thesaurus file by matching key words. This will both conserve file space and enable synonymous diagnoses to be retrieved efficiently. The basic thesaurus and code are based on S.N.O.P. (Systemized Nomenclature of Pathology) because of its wide usage and comprehensive modern terminology. Name: Lamb, E. Project: EMPIRE Department: Gynecology - Obstetrics Project Description: Calculation of relative potency and confidence limits for total gonadotropin bioassay. Used primarily for research but will also be used (C 1 assay per month) for calculations involved in service work--even these assays may be used in a research project. Name: Lederberg, J. Project: GENBWT Department: Genetics Project Description: Study of characteristics of unusually high birthweight relative to IQ, diseases, parent income, educational background, parity, and sex of child. 128 Grant No. RROOQ311-04 Section IV Name: McGann, L. Project: HOSPCOST Department: Community & Preventive Medicine Project Description: Tabulate the results of a sample survey of Stanford Medical Center hospital charges for the aged. The purpose of the study is to compare 1968 costs and sources of financing with parallel results of a 1962 study in the Stanford Medical Center. Name: Mesel, =. Project: CLINIC Department: Pediatrics Project Description: The object of this project is to store patient identi- fication information and diagnoses obtained at each step in the course of illness (clinical - OPD or IPD, cardiac catheterization, surgery, and autopsy) in the ACME files. This wark is patient-service oriented but has several experimental aspects such as the structuring of the filing schemes to permit rapid access (while conserving the amount of file space utilized) and the utilization of the stored information for hos- pital planning purposes, evaluation of patient survival with different modes of therapy, etc. 1e9 Grant No. RROO311-04 Section IV Name: Mesel, E., Project: WFR Department: Pediatrics Project Description: Investigation of mathematical modeling techniques applicable to medical diagrams. The plan is ultimately to apply the cause-effect modeling techniques developed in an environment that allows on-line interaction between physician and computer model. Though a program has been written to implement the cause-effect modeling techniques using a Burroughs B5500 computer, adapting even that program to ACME will require considerable effort as the program depends heavily on the nearly unique ability of the B5500 to efficiently handle re- cursion and treat overlay automatically. It is felt that the ability to experiment with the models constructed in a way available only in an on-line system and that the increased interest and criticism that will result from testing the models produced in a clinical environment justify the effort, Currently programmed is the congenital heart disease model of Warner and his collaborators. Name: Morrell, L. Project: EEG Department: Neurology Project Description: The initial project will be multivariate statistical evaluation of data relating electroencephalographic measures to motor behavior. The data to be entered in ACME have already been partly processed with a LINC computer; period analysis of spontaneous EEG and also amplitude analysis are used as predictive variables for sub- sequent performance by the human subject, Analysis will be reiterated to afford comparison of electrocortical activity at various regions. Other uses will be analysis of averaged cortical evoked responses to sensory input, and averaged cortical activity preceding and following voluntary action, including speech production. Statistical evaluation of such data as recorded simultaneously from a variety of electrode locations is planned. 130 Grant No. RROO311-o4 Section IV Name: Noble, E. Project: ALCOHOL Department: Psychiatry Project Description: We have been studying the effects of alcohol on the central nervous system of rodents. A study of alcohol's effect on the pituitary adrenal system is being studied in various inbred mouse strains. We are also studying the effects of central nervous system lesions on alcohol preference phenomenon in mice. Finally, the mechanism of cen- tral nervous system adaptation to alcohol and other stressors is being considered. Name: Whitcher, C. Project: spetrm Department: Anesthesia Project Description: Spectral analysis of blood pressure sounds. Determine why blood pressure sounds are difficult to hear under adverse circum stances, 131 Grant No. RROO311-04 Section IV Category 12 Name: Angel, R. Project: ERCORECT Department: Neurology Project Description: Data reduction and statistical analysis of movement pat- terns, limb displacement, limb velocity, and electromyography in relation to both normal subjects and neurologically impaired patients. Name: Constantinou,’ C. Project: UROL Department: Urology Project Description: ACME will be used for research in the Division of Urology for real-time data acquisition and feedback. Analogue data collected from anesthetized animals in surgery will be transmitted via the interface box to the 1800 and 2741 output re- ceived in the operating room during the experiment. There are four input channels now for parameter input such as action potentials from ureteral smooth muscle, peristetic pressure waves, urine flow rate, EKG or blood pressure, The analogue output is used for driving the XY plotter and providing a reference for servomechani- cal pump. During experiments data files are written from the analogue inputs for long-term storage and also for short term (up to two weeks) before data reduction. ACME will also be used for statistical analysis of the experimental work and the TV for display of waveforms and graphs. 132 Grant No. RROO411-01 Section IV Name: Duffield A. Project: CHEM Department: Chemistry Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experimental analysis programs so ag to develop programs for the routine analysis and finished output of mass spectra. The trans- mission is through the 270Y-270X channel. The project plans to develop this interface to service two mass spectrometers (ALTAS CHY and ART MS9). The taken spectra are then to be fed to the Artificial Intelligence group under the supervision of Joshua Lederberg and Edward Feigenbaum to be used in their investigations. (B) Another use of data transmission through the 270Y is to take spectropolorimeter measurements and then analyze these spectra for form bandwidths, and similarities between derivatives for theoretical projections. (C) The project mentioned also includes a battery of utility programs for metastable analysis, chemical rate analysis, C13 substitution ratios, and other routine analyses that the chemists wished programmed. Name: Gersch, W. Project: SYNTHEST Department: Neurology Project Description: Research in the application of time series methods to problems in neurophysiology and medicine. 1) Development and application of new multidimensional autoregressive representation methods of spectral analysis to EEG analysis. 2) Development and application of a time series analysis technique to locate the anatomical site of epileptic focus from data taken from deep brain site implanted bipolar electrodes during generalized epileptic seizure activity. 3) Research on modeling feedback paths in the cat's visual system. Ex- perimental data taken in the laboratory of Dr. K. L. Chow. 4) A eritieal computer analysis of a long standing model of vagus con- trol of heart rate, 5) Development of a novel Markov chain-symbol pattern recognition pro- cedure applied to recognition of cardiac arrhythmias using R-R interval data. 133 Grant No. RROO411-04 Section IV Name: Reynolds, W. Project: DREAMS Department: Genetics Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experimental analysis programs so as to develop programs for the routine analysis and finished output of mass spectra. The trans- mission is through the 270Y-270X channel. The project plans to develop this interface to service two mass spectrometers (ALTAS CH4 and AEFI MS9). The taken spectra are then to be fed to the Artificial Intelligence group under the supervision of Joshua Lederberg and Edward Feigenbaum to be used in their investigations. (B) Another use of data transmission through the 270Y is to take spectropolorimeter measurements and then analyze these spectra for form, bandwidths, and Similarities between derivatives for theoretical projections. (C) The project mentioned also includes a battery of utility programs for metastable analysis, chemical rate analysis, C13 substitution ratios, and other routine analyses that the chemists wished programmed. Name: Ross, R. Project: CHEM Department: Chemistry Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experimental analysis programs so as to develop programs for the routine analysis and finished output of mass spectra. The trans- mission is through the 270Y-270X channel. The project plans to develop this interface to service two mass spectrometers (ALTAS CH and AEFI MS9). The taken spectra are then to be fed to the Artificial Intelligence group under the supervision of Joshua Lederberg and Edward Feigenbaum to be used in their investigations. (B) Another use of data transmission through the 270Y is to take spectropolorimeter measurements and then analyze these spectra for form, bandwidths, and similarities between derivatives for theoretical projections. (C) The project mentioned also includes a battery of utility programs for metastable analysis, chemical rate analysis, C13 substitution ratios, and other routine analyses that the chemists wished programmed. 134 Grant No. RROO311-01 Section IV Name: Stillman, R. A. Project: DREAMS Department: Chemistry Project Description: The purpose of this project can be summarized as follows: (A) The taking of high rate data transmission to write experimental an- alysis programs so as to develop programs for the routine analysis and finished output of mass spectra, The transmission is through the 270Y- 2fOX channel. The project plans to develop this interface to service two mass spectrometers (ALTAS CH4 and AEI MS9). The taken spectra are then to be fed to the Artificial Intelligence group under the supervision of Joshua Lederberg and Edward Feigenbaum to be used in their investigations. (B) Another use of data transmission through the 270Y is to take spectro- polorimeter measurements and then analyze these spectra for form, band- widths, and similarities between derivatives for theoretical projections. (C) The project mentioned also includes a battery of utility programs for metastable analysis, chemical rate analysis, C134 substitution ratios, and other routine analyses that the chemists wished programmed. 15 Grant No. RROO411-0} Section IV Category 13 Name: Assaykeen, T. Project: RENIN Department: Urology Project Description: We have previously reported that in dogs insulin- induced hypoglycemia significantly increases plasma renin levels. We would like to continue these studies in order to attempt to deter- mine what the stimulus to renin secretion is under these conditions and how this stimulus is transmitted to the juxtaglomerular cells. There is good evidence that the sympathetic nervous system can in- fluence renin secretion but how this occurs is not known. We would like to establish whether catecholamines stimulate renin secretion through alpha or beta receptors, whether cyclic 3', 5'-AMP is in- volved and whether the effects of the catecholamines on renin se- cretion can be separated from the effects of these compounds on renal hemodynamics and function. The results of such studies may lend support to existing theories regarding the control of renin secretion or may give new insight concerning the physiologic control of this important endocrine system, 136 Grant No. RROO311-04 section IV Name: Cohen, 8. Project: DRUGALRT Department: Pharmacology Proj Name: ect Description: The project involves the establishment of a computer- based program aimed at preventing undesireable drug interaction and reducing drug toxicity at the Stanford University Medical Center. A data bank utilizing already available information from the pharmacologi- cal literature will be compiled dealing with drug interactions of clini- cal significance, When prescriptions are billed by the Stanford phar- macists, they would type the name of the drug and the dosage regimen into a terminal located in the Hospital pharmacy. When a new drug added to a patient's regimen ineracted with any one of the several drugs a patient may already be receiving, the computer would print out an appropriate alert accompanied by a literature reference, which would be sent to the nursing unit by the pharmacist--together with the drug. Prior to administering a drug accompanied by such an "alert", the nurse would contact the physician in charge, who would take the patient's total clinical condition into account in deciding whether or not the drug should be administered. This program would provide considerable teaching benefitsto students and house staff, in addition to providing benefits of major importance to patient care. In addition, it would be possible to assess the impact of providing physicians with drug inter- action information in such a direct fashion, and also to learn in a prospective way about the clinical effects of incompatible drug com- binations that are administered for one reason or another despite the alert, DeNardo, G. Project: XENONL33 Department: Nuclear Medicine Project Description: This project involves the use of radioactive methods to assess the regional distribution of ventilation and pulmonary blood flow in normal subjects and subjects with disease. A scintillation camera and special purpose computer are used to generate positimal and quantitive information for subjegnent processing by ACME. Studies in upright man have revealed that the distribution of ventilation is determined by the pre-inspiratory and inspiratory volumes. We propose to study pulmonary embolism with these radioactive methods and compare the results with those obtained from conventional pulmonary function studies. 137 Grant No. RROO3Z11-04 Section IV Name: Fries, Jd. Project: DATABANK Department: Medicine-Immunology Project Description: Concerned with the problem of establishing significant clinical, pathologic, and laboratory correlations in the immunologic diseases, and assessing these correlations in regard to classification, pathogenesis, prognosis, and response to therapy. These diseases are characterized by involvement of a large number of organ systems, a large variety of associated laboratory abnormalities and a course prolonged in duration and punctuated with periodic exacerbations and remissions. A massive amount of data is thus generated by each patient and meaningful correlations may be obscure to the clinician and inaccessible to the clinical researcher. The data cannot be well-handled retrospectively or manually. We have evolved an ordered, comprehensive method of recording patient data structured with respect to time. We propose to establish a compu- ter data bank for storage of this structured information and to develop programs for searching the data bank in a variety of ways to provide the desired correlations and statistical analyses. Name: Govan, D. Project: PARAQUAD Department: Urology Project Description: The Division of Urology at Stanford is currently res- ponsible for the urologic evaluation management and clinical follow-up of nearly 300 patients with spinal cord injury or disease. Utilizing the ACME Computer Facility between July 1967 through the present time, we have developed a method of information storage and retrieval which promises to be of considerable assistance to us in the overall manage- ment of this group of patients. 138 Grant No. RROO411-04 Section IV Name: Kakihana, R. Project: ETHANOL Department: Psychiatry Project Description: We have been studying the effects of alcohol on the central nervous system of rodents. A study of alcohol's effect on the pituitary adrenal system is being studied in various inbred mouse strains. We are also studying the effects of central nervous system Lesions on alcohol preference phenomenon in mice. Finally, the mechan- ism of central nervous system adaptation to alcohol and other stressors is being considered, Name: Kriss, J. Project: ASSAY Department: Nuclear Medicine Project Description: This program is used to calculate the results of a bioassay for the long-acting thyroid stimulator, (LATS), to calculate the statistical significance of these results, and to calculate the results of radioimminoassays for TSH, FSH, LH, growth hormone, anti- sperm antibody, anti-thyroglobulin, anti-microsomal antibody, and LATS. These data are being acquired as part of a study on the patho- genesis of Graves' disease, the effects of X-ray therapy upon thyroid function, and the pathogensis of other endocrine disorders associated with autoimmunity. 149 Grant No. RROO311-04 Section IV Category 14 Name: Dong, E. Project: heart Department; Cardiovascular Surgery Project Description: Study effects of heart transplantation. Collecting data on blood volume, heart rate, rhythm, and blood pressures, Also, developing relationships between white cell types--correlations and negative correlations. Name: Dong, &E. Project: MARGL Department: Cardiovascular Surgery Project Description: The purpose of our project is to develop a controller for an artificial heart. We are attempting to do this by using a trans- fer function between arterial pressure and heart rate. The project is a joint concern between the Department of Cardiovascular Surgery and the Stanford Electronics Laboratory. At the present time, we are recording three channels of analog data from an auto-transplanted dog. This data is processed using the ACME 1800 system, The data are converted to digital data using the 1800 and stored in the 360/50. It is then processed and six channels of data are calculated. The digital data is then converted to analog signals using the 1800 and printed out on an offner strip chart in the laboratory. We also have a PDP-8-360/50 interface which we use to store PDP-8 data on the ACME system. 140 Grant No. RROO311-o4 Section IV Name: Mesel, E. Project: VSD Department: Pediatrics Project Description: This project is concerned with blood flow through ventricular septal defects (VSD) surgically produced in dogs. Two major sets of comparisons are made: the pattern of flow through the VSD is compared with the pattern of differential pressure between the left and right ventricles and with the electrocardiogram (ECG); and flow measured by an electromagnetic flow probe (which we consider a primary standard) is compared with flow measured by other techniques used on people (Fick dye dilution). During the experiment VSD flow, left and right ventricular pressures, and the ECG are recorded on tape. The more interesting data are selected for A to DP conversion and for computation of the differential pressure by program WORKHORSE. Program LISTING lists digitized data, which, when graphed, permits comparison of the pattern of flow with the pat- tern of differential pressure. As might be expected, we have found that these patterns are very similar even under varying conditions (e.g., ectopic beats), with flow slightly delayed with respect to pressure. Program cathlog produces a file which summarizes all our VSD experiments. Future effort will be directed towards the incorporation and use of programs developed in project carcat for pattern recognition of pres- sure and flow contours, Name: Morris, S. Project: EXPT4 Department: Genetics Project Description: I am using the 1800 to interface a Packard liquid scintillation counter to the 360. This allows me to feed raw data directly into the 360 where it can later be retrieved and digested. ACME will be used to analyze the incorporation of radiolabeled amino acids into brain proteins. Wa Grant No. RROO311-o0l Section IV Name: Smith, N. Project: MAC Department: Anesthesia Project Description: This project involves calculation of cardiovascular data from variables obtained in normal volunteer subjects and patients. No statistical analyses are performed through this program; rather they are performed separately using standard programs. Name: Smith, N. Project: BABOONS Department: Anesthesia Project Description: This project involves transfer of manually obtained and calculated data into ACME files. Multiple regression and correlation analyses are then performed on these data. Data obtained by destructive methods (thoracotomy, catheter placement, etc.) are compared to those obtained by nondestructive methods (microphones, accelerometers, etc.). It is hoped to replace the former with the latter. we Grant No. RROO311-04 Section IV Name: Thathachari, Y. Project: DOPA Department: Dermatology Project Description: Structure of melanins, Melanin is a polymeric pigment widely distributed throughout the plant and animal kingdoms. It has unusual physical and chemical properties. Using ACME as a real-time terminal, models of the molecular structure of melanins were generated starting with the known shape of the subunits and using various criteria for the linking of adjacent units. By watching the output periodically, the flow of the computation could be directed at will. For these genera- ted models, various measurable physical data were computed and compared with the experimentally derived values. Programs were especially written for these calculations and were found to be very promising and fruitful. Some of the results have been published and presented at conferences and more publications are under way. In view of the success of the techniques, the work is being continued. Radioactive tracer techniques for the detection and therapy of melanomas-- improvement on the conventional scanning techniques making more efficient use of observations with a real-time feed back between the collection of data and their processing. Simulated experiments using ACME as a real- time terminal are under way to make a choice between alternate techniques. When the choice is made, we plan to commission the equipment and the interfacing with ACME. 143 Grant No. RROO311-04 Section IV Name: Warrick, G. Project: STEROID Department: Psychiatry Project Description: The present research in our psychophysiological labora- tory revolves around the "averaged evoked response." We record a con- tinucus EEG on magnetic tape when presenting selected stimuli. After- words it is necessary to take out the EEG from the recording for certain time periods after each stimulus and average from 25 to 100 curves. When more than one kind of stimulus is shown the EEG must be distributed according to specific stimuli and several averages calculated simultan- eously. ACME supplies us with 3 analog input lines for reading of the EEG and corresponding signals. Our sampling rate is 4 msec and by reading 100 curves for 500 msec or 25 curves for 4 sec, we use a storage space of 25000. After the curves are selected and averaged, they are returned through an analog output line and plotted on our X-Y plotter. The curves are also stored in digital form in the ACME file system. We are presently having a second output line installed to give us a time base for the x-axis on the plotter. The two output lines will be connected for more systematic results. 14h Grant No. RROO311-04 Section IV Name: Wittner, W. Project: AROGUESS Department: Psychiatry Project Description: (AROGUESS) The influence of correctly and incorrectly guessed visual patterns on visual averaged evoked response. This study deals with changes in the electroencephalogram (EEG) of human subjects under conditions of various "mental states." The EEG associated with certain visual stimuli in certain "mental states" will be averaged to obtain the so-called averaged evoked response (AER). The shape of the AER waveform reflects brain activity beyond the purely sensory-receptive component. For instance, the AER is influenced by such variables ag attention, conditioning, and habituation. in this study, young healthy males will be presented with a sequence of two types of visual stimuli which will alternate randomly. One pres- entation will consist of a cueing flash, an arrow pointing left, anda test flash. The other visual stimulus presentation will consist of a cueing flash, an arrow pointing right, and a test flash. Prior to each presentation, the subject will make a guess as to the type of upcoming presentation by pressing either a left-handed or a right-handed button. On the basis of results of related studies by other investigators, it is assumed that the evoked response to correctly guessed arrows will differ from that evoked by incorrectly guessed arrows. One purpose of the study will be to ascertain whether indeed this is so. Furthermore, it is hypothesized that the AER induced by flashes following incorrectly guessed arrows will differ in shape from the AER averaged on flashes following correctly guessed arrows. The assumption is made that guess- ing correctly produces a different "state of mind" than guessing in- correctly and that this "state of mind" persists long enough to alter the AER to a rapidly following neutral light stimulus. The various AERs will be differentially averaged to prove or disprove the stated hypotheses, The averaging of the EEG to obtain the AER will be done by the use of ACME computers. Once the various AERs are averaged, they will be anal- yzed and compared with each other, again by use of the ACME facility. Data (at various stages of analysis) will be stored in computer files. Should the hypotheses prove to be correct, further research will be conducted to investigate the effects of hormones on these parameters. 145 Grant No. RROOZ11-0}4 Section IV Category 15 Name: Aronow, L. Project: LCEL Department: Pharmacology Project Description: Routine laboratory calculations, including statistical tests of significance, relating to the mechanism of action of anti-cancer drugs. Name: Bagshaw, M. Project: SUMMARY Department: Radiology Project Description: The project is designed for retrieval of cases and classification of cases from the tumor registration. The ACME Computer is used for: 1. Gathering case histories and follow-up information from patients with tumors treated by radiation therapy. 2. Generating reliable data for the therapist's use in either research work or patient treatment. 146 Grant No. RROO311-04 section IV Name: Baldwin, R. Project: OLIGOMER Department: Biochemistry Project Description: The project is characterization and helix -- forming properties (both kinetic and equilibrium properties) of short DNA helices formed by dAT oligomers of defined chain of lengths. dAT oligomers have the repeating and self-complementary base sequence ...ATAT... . They may form either hairpin helices or dimmer helices, depending on conditions. The aims of the project are: (1) characterization of loops in DNA helices, (2) measurement of the parameters controlling the cooperativity of DNA melting, and (3) measurement of the rates of the elementary steps of base pair opening and dosing in DNA helices. Name: Bausek, G. Project: HODPAT Department: Medicine - Infectious Diseases Project Description: Lymphoma data program (LDP). The radiotherapeutic treatment of lymphomas, particularly Hodgkin's disease, has been shown to be the most effective way of achieving high cure rates. However, many aspects of these malignancies are still puzzling. For example, in addition to the obvious truth that we are still in the dark regarding the origin of lymphatic cancer, there appear to be significant differences between the lymphomas in their methods of progression, both in the presence and absence of treatment. The LDP has as its initial goal the accumulation of data on many aspects of lymphoma patients in readily retrievable form. Items of importance are: results of physical exams of new patients, background information such as records of malignancies in the patients' families, early symp- toms of the disease, laboratory data, method of treatment, and follow- up data (recurrence, retreatment, etc.). From the analysis of such stored information, it is anticipated that inferences can be drawn regarding optimum treatment scheduling and the possible causes of these diseases. 17 Grant No. RROO411-0%4 Section IV Name: Beard R. Project: PREVMED Department: Community & Preventive Medicine Project Description: Making correlation computations. Analyzing behavioral responses and influences of inhaling carbon monoxide, Name: Bodmer, W. Project: POPGEN Department: Genetics Project Description: Our main use of ACMF is for the analysis and interpretation of data on human white cell antigens. A secondary use is for the analysis and simulation of population genetic models. We have developed a series of programs to facilitate the storage of our data with appropriate editing at the time of input and to facilitate a read interaction between the experimental worker and the computer. This allows us, at short notice, to do small scale 2 x 2 analyses for serum characterization, selection of appropriate individuals for absorbtion and automatic typing according to complex patterns of serum reaction. These increased opportunities for interaction with the computer have been a great help in our day-to-day work and in establishing new relationships amongst our sera. Our future plans include the development of programs for the systematic analysis of family data, 148 Grant No. RROO311-04 Secticn IV Name: Brutlag, D. Project: ULTRA Department: Biochemistry Project Description: During the past several months I have been studying the role of divalent metal ions in the reaction mechanism of the enzyme DNA polymerase, In this work I use ACME to perform nonlinear weighted re- gression analysis of the data I have in order to test various theoretical models which describe how the enzyme works. I also use ACME routinely as a general laboratory tool in the reduction of all of my experimental data. One program reduces data from enzymatic assays and prepares a writ- ten report. Another calculates binding constants from equilibrium dialysis experiments. I have also used ACME for calculating physical parameters of macromolecules from data obtained from the analytical ultracentrifuge. Name: Cady, P. Project: THYROID Department: Psychiatry Project Description: Thyroid function is being studied in human subjects of varying genetic backgrounds subjected to stress, Measures of thyroid function include iodine uptake, thyroidal iodine clearance, thyroxine turnover, free and total thyroxine, and thyroxine binding capacity. Psychological measures of stress include personality in- ventories, mood scales, I & E scales, coping scales, and scored psy- chiatric interviews, Biological measures of stress include cortisol levels, pulse, diastolic and systolic blood pressures, and auditory reaction times. Measures of genetic inheritability are made using Falconer's family incidence equations. The computer is clearly necessary to perform the analysis of variance with such a large number of variables. 1g Grant No. RROO411-04 Section IV Name: Collins, K. Project: ATCase Department: Biochemistry Project Description: This file is used for three purposes. First, it is used in a variety of ways as a research tool. It has been used to compute the dissociation constants for an enzyme (ATCase) and some of its inhibitors. It will be used in the future to simulate difference from model compounds and compare these spectra with the experimental spectra and to analyze data from equilibrium dialysis studies of ATCase and its substrates and inhibitors, Second, it is used as a data processing facility for research-generated data. It is extensively and routinely used to process chromatograms from an amino acid analyzer; a long program stored in ACME provides a variety of different procedures that may be used on the data, Third, it is used as an education device. For instance, this file has been used to process data from a laboratory course in ultracen- trifugation. Name: Conner, R. Project: RATRACE Department: Psychiatry Project Description: There are approximately 15 individuals in this laboratory directly involved in experimentation relating neuroendocrine function to behavior. Information from animal testing chambers will soon be recorded on a high-speed paper-tape punch. The data on the paper- tapes will be dumped directly into ACME data files through a PDP-8 inter- face, or listed by the PDP-8 for keyboard terminal input to ACME. In either case, a program in the permanent ACME files will be written to sort the data from the several experiments recorded simultaneously on the paper-tape. Appropriate programs for the analysis of data from specific experiments will also be maintained in the permanent program files. In addition, we plan to use the ACME system to reduce and analyze data derived from experimentation which does not involve use of our paper-tape recording system, e.g., adrenocortical steroid levels of animals under various conditions and ACTH bioassay data. 150 Grant No. RROO411-0%4 Section IV Name: Fung, D. Project: HARTFORD Department: Anesthesia Project Description: Study of acute ventilatary insufficiency, includes research in: 1) mechanics and gas exchange in patients with ventilatary insuffi- ciency, 2) clinical research in post-operative respiratory complication, 3) cardio-pulmonary failure, 4) respiratory distress syndrome of newborn, 5) drug intoxication, and 6) pulmonary blood flow and pulmonary hyper- tension. ACME is used in these studies for: 1) statistical analysis, 2) program files for computation of physiological parameters from blood gas and other data, and 4) A-D conversion and processing of respiratory data in computation of cardiac output, and respiratory variables. Name: Fung, D. Project: RESPUNIT Department: Anestheisa Project Description: Objective: To determine the response of the pulmonary circulation to changes in inspired gas composition and intra-treacheal pressure. Progress to date: Apparatus has been set up for measuring pulmonary blood flow from exhaled gas composition and a program is al- ready available to compute the results. Current work: 1) Refinements are being made to improve the accuracy of the pulmonary blood flow measurement, and 2) a pilot study is being started to observe the ef- fect of a change in inspired gas composition on pulmonary artery pres- sure. Intended computer use: Computation results from data a) calibra- tion curves are computed, b) data is converted, ¢c) results are computed, and d) statistical parameters are calculated, 1b1 Grant No. RROO411-04 Section IV Name; Glattke, T, Project: ENG Department: Otolaryngology Project Description: We are collecting data on an almost daily basis from a group of preparations with electrodes implanted in the auditory nervous system. Use of ACME for analyses requiring many replications of an operation (e.g., in auto-correlation) is advantageous. Over the next few months, we anticipate attempting a feasibility study to determine if ACME would be useful for patient categorization. Our general thinking is that files containing coded history and test find- ings would be updated on a daily basis, so that these might be avail- able for a trend analysis. (For example, the audiological examination on a given patient may incorporate as many as half-dozen tests. Patient selection for a given course of treatment or additional special testing would seem to be enhanced by the availability of such trend analyses. ) Name: Goldstein, A, Project: PHAlL Department: Pharmacology Project Description: All-purpose programs for statistical and curve- fitting procedures for laboratory studies on morphine, especially on development of tolerance and dependence. Name: Goldstein, D,. Name: BARB Department: Pharmacology Project Description: Largely least-squares curve-fitting programs for establishing essential parameters for enzyme kinetics in inhibition of flavin enzymes by barbiturates. 152 Grant No. RROO311-04 Section IV Name: Hackney, J. Project: PHAL Department: Pharmacology Project Description: All-purpose programs for statistical and curve-fitting procedures for laboratory studies on morphine, especially on develop- ment of tolerance and dependence. Name: Hilf, F. Project: TESTA Department: Psychiatry Project Description: Involves psychological testing of psychiatric patients using on-line interactive techniques in which the patient sits at the terminal and is asked questions and he gives the answers and is rein- forced by the computer. A bravity procedure is also incorporated in this program. The main purpose is to determine if paranoid psychiatrie patients respond to feedback differently than a control group of other psychiatric patients. Name: Hwang, J. Project: BWISTUDY Department: . Genetics Project Description: Study of birth weight and IQ in relation to sex, parents, education, race, and income, 155 Grant Nc. RROO311-o4 Section IV a Name: Kaplan, B. Project: PSYCHO Department: Psychiatry Project Description: The general nature of the project is the investigation of the relation of automatic nervous system (ANS) responses to attentional sets (thinking and environmental observation). In a recently completed study, which examined ANS changes as a function of verbalization and environmental attention and rejection, ACME was used to obtain heart rate and skin conductance values from raw data. This physiological data was then analyzed, using analysis of variance and other parametric statistical procedures. In addition, ACME was used for obtaining correlations between the physiological responses and personality variables. Future work will look at ANS responses in lactating and non-lactating human females and will investigate ANS correlates of attention and infor- mation processing. ACME will be used for transformation of the raw physiological data into meaningful units and the statistical analysis of this data, Name: Kapp, DP. Project: CHBR Department: Radiology Project Description: Data analysis of sedimentation patterns of DNA following X-irradiation, Name: Kessler, 8. Project: MATSPEED Department: Psychiatry Project Description: Will be analyzing mating speed experiments as previously, including use of linear regression and anelysis of variance programs. 154 Grant No. RROO411-04 Section IV Name: Kriss, J. Project: BLDVOLL Department: Nuclear Medicine Project Description: The program is being used to calculate plasma volume, blood volume and red cell mass in patients who receive radioactive tracer material. The determination is useful in the evaluation of patients with anemia and polycythemia. Name; Lederberg, J. Project: GENLIBL Department: Genetics Project Description: This project contains the statistical and miscellaneous programs used by the Genetics Department. Statistical programs: General statistical analysis for the calculations of sum, mean, standard deviation, the analysis of variance, chisquare and probability of chisquare distribution, correlation and regression analysis, the normal distribution with the same mean and standard deviation for fitting a curve. Plotting Programs: Plot bar graph in 100 positions, plot of percentage dis- tribution, plot by function scaled to the range of 0 to 100, plot of multivalued function allows the choice and supersition of several characters. Flag is inserted on the chart when underflow or overflow occurred. Sorting Programs: Sorting a vector in ascending order, sort array and alphabetical informations. 155 Grant Wo. RROOZ11-04 Section IV Name: Leiderman, P. Project: PREMIE Department: Psychiatry Project Description: Studies of maternal behavior in non-human mammals have suggested that the degree of interaction permitted between mother and infant in the postpartum period influences later maternal attachment and infant development. Assessments of each mother and her infant are made periodically during the time the infant is hospitalized and during the first two years at home. Three major areas are included in these assessments: 1) maternal attitudes regarding her relationship with the child as reflected in res- ponses to interviews and questionnaires, 2) maternal behavior observed during routine caretaking of the infant, and 4) the behavioral deveLlop- ment of the infant. Analyses will be done comparing the different groups on various attitu- dinal and behavioral dimensions at specific points in time as well as changes within groups over the two year period. We will also examine the interrelationships between variables as well as the effects of birth order and sex of the infant on the variables of interest. 156 Grant No. RROO311-04 Section IV Name: Luetscher, J. Project: Blood-pr Department: Medicine - Metabolic Research Project Description: Our research project deals with the secretion and metabolism of adrenal hormones. Various steroid hormones, catecholamines, and trophic hormones are measured under different conditions of sodium loading or sodium depletion. We attempt to define and relate groups of measurements which assist in the identification of curable forms of hypertension. The ACME system is used in this project in several ways: (1) To assist in the calculation of laboratory data, involving difficult procedures, such as the double isotope derivative method, which requires solution of simultaneous equations. (2) Interpretation of data: (a) Simulation of complex systems (for example, the study of reactions in which substrate and enzyme concentrations are regulated by different systems and may vary inde- pendently; or distribution and metabolism of hormones). (b) Statistical analysis (comparison of mean and variance of different groups, or correlations between different observations). (c) Analysis of clinical information (the association between different observations, or the effects of drugs, diets, etc.). (3) Data files are used to store information at various stages of a sequential process, and for collection and analysis of the large amount of clinical and laboratory data which accumulates during a long investigation, (4) The computer has been used extensively in research training of fellows and staff, first in principles and techniques of computer use, and subsequently in practical applications. LT Grant No. RROO311-04 Section IV Name: Melges, F. Project: TEMPO Department: Psychiatry Project Description: Relating changes in temporal experience to changes in psychopathological symptoms such as depersonalization and delusions. Our plan is to discover how aberrations in temporal sequencing and dis- tinquishing memories from perceptions and expectations relate to the emergence of definable psychopathological processes, The overall notion for a number of sub-projects is: confusing past, present, and future underlies the central symptoms of psychosis. Sub-projects involve specific attention to drug-induced psychoses and certain symptoms of psychoses, especially depersonalization, changes in body image, paranoid delusions, and feelings of influence or alien control. Previous work has demonstrated that this approach is highly useful for understanding psychotic processes. Although aggregate data across sub- jects will be used, the usual approach will be the intensive study of Single subjects as they change over time. This allows for the study of what changes with what over time. In other words, various processes, i.e. sequential relationships between changes, are discovered by this intensive approach. 158 Grant No. RROO311-04 Section IV Name: Miller, R. Project: BIOSTOP Department: Community & Preventive Medicine Project Description: The Division of Biostatistics, Department of Community and Freventive Medicine, provides biostatistical consulting to persons doing medical research in the Stanford Medical Center and occasionally elsewhere, such as Presbyterian Hospital in San Francisco. Biostatistics also trains postdoctoral fellows and some graduate stu- dents in Statistics in biostatistical consulting. Investigations of statistical methods may also be done by the staff, postdoctoral fellows, or graduate students. The ACME computer is used in all these activities. Name: Miller, 2. Project: THESES Department: Community & Preventive Medicine + Project Description: This "project" will be used for computing done by or for graduate students in statistics and biostatistics as part of the research necessary for their theses, or otherwise connected with their education. Name: Miller, R. Project: COURSES Department: Community & Preventive Medicine Project Description: This "project" will be used for computing done by or for the staff in connection with the teaching of courses in biostatistics. 159 Grant No.RROO411-04 Section TV Name: Nelsen, T. Project: ADRENAL Department: Surgery Project Description: Clinical cancer research record protocols and data for storage and analysis. Next step will be display routines. Name: Payne, R. Project: SERNAL Department: Medicine - Hematology Project Description: The research is concerned with extending and classi- fication of leukocyte and/or tissue antigens by serologic and genetic analysis of specific human antisera. In the computer programs, 1) donor-recipient pairs of individuals are selected for deliberate immuni- zation to produce antisera, and 2) the antisera are analyzed by comparing their reactions with test cells in 2 x 2 tables for associations between them. The significant associations are calculated, and the frequency of positive reactions are determined. 160 Grant No. RRCOS11-04 section IV Name: Porter, R. Project: ATC_KIN Department: Biochemistry Project Description: Project ATC KIN has been used for data processing in the investigation of the steady~state kinetics of the enzyme, aspartate transcarbamylase. The programs were written for curve-fitting the data from different types of kinetics experiments. For example, program "DataFit" employs a simple linear least squares fit to calculate the initial rate of reaction from the raw data, measured as amount of radioactivity versus time of reaction, and converts the result to standard units of specific enzyme activity, using units of concentration. Other programs calculate the kinetic parameters using a linear least squares fit for the reciprocal transformation, due to Lineweaver and Burke, of the Michaelis-Menten equation. Another program, "Hyper- Fit", was written to fit the non-linear, hyperbolic function of the original Michaelis-Menten equation. The program employs a reiterative procedure of trial-and-error testing for optimal fit. Trial values for the two parameters of the Michaelis-Menten equation are tested for minimizing the residual, and the procedure is reiterated to give a close approximation of the best values. This computational procedure was refined and optimized for speed, and the program will compute the best values for the two parameters, to an accuracy exceeding that of the data, in less than ten seconds of computer time in a time-sharing environment. This approach proved to be so successful that it was adapted for curve-fitting other, more complex non-linear kinetic equations with more parameters. For example, the non-linear equation describing substrate inhibition, with three parameters, which does not give a simple linear reciprocal transformation, has been employed directly, using this trial-and-error technique. In addition, the family of hyperbolic curves described by the equation for competitive inhibition, with three parameters, has been employed successfully. The greatest success of this technique has been the use of equations with four parameters for curve-fitting, such as the equations describing non- competitive inhibition and parabolic competitive inhibition. With correspondingly longer times for calculation, these programs have pro- vided quantitative support for the existence of certain reaction inter- mediates in the pathway of this enzyme mechanism. These programs make special use of the on-line communication available with the ACME system, especially through the use of options and operator- controlled branchpoints in the programs. 161 Grant No. RROO311-04 Section IV Name: Reaven, G. Project: DISPLAY Department: Medicine - Metabolism Project Description: 1) Derivation of a three compartment model describing disappearance of plasma insulin. 2) Evaluation of the dog as an experi- mental model for study of insulin distribution in man. 3) Digital on-line computer display to investigate the structure of metabolic systems. In- terested in developing models of glucose, insulin, and triglyceride kine- tics ag related to diabetes mellitus and atherosclerosis. Clinical data obtained from tracer studies are analyzed by the ACME computer through five stages of development. The project DISPLAY includes the third and fourth stage. The third stage contains the program PEEL that automati- cally obtains the parameters for a linear sum of constant coefficients of a system of linear differential equations. The results are used for the fourth stage. In this phase, the parameters are used for calculation of a theoretical curve which is displayed on a CRT. It is then compared with data which also appears on the CRT. The results of PEEL and SKINNER enable us to change parameters until we obtain a satisfactory visual fit. In this phase, we used the programs RUNGCURV, DATA, TDATA, berman, RUNGPLOT, and RUNGFUN. We are now performing similar analysis with res- pect to triglyceride metabolism and are extending the insulin work. We expect to use the above procedures the entire year and expect to extend stage four and develop stage five for analysis of non-linear metabolic models. 162 Grant No. RROOZ11-o4 Section IV Name: Reaven, G. Project: FIT Department: Medicine - Metabolism Project Description: (See discussion in Project DISPLAY). The final phase is at the present being developed. The results of simulation in stage h is to be statistically evaluated to see if the parameters obtained do not violate the statistical limitations of the data, At the moment, we are doing this in batch mode at the Computation Center. However, the most satisfactory results are obtained if the statistical evalua- tion is coupled to stage 4, We plan to use nonlinear regression techniques to evaluate these parameters. We have developed two pro- grams for this procedure; they are RUNGPOW and EXPOPOW, which call two programs, POWELL and COVARE, which are stored on public file. Name: Reaven, G. Project: PAT DATA Department: Medicine - Metabolism Project Description: (See discussion in Project DISPLAY). This project includes stage 1 and stage 2. Stage 1 and stage 2 are support pro- grams for stages 3, 4, and 5. In stage 1, serum endogenous insulin is biologically assayed by the program INSULIN. The program TCCONRAD determines triglyceride concentration and the program DOUBLE estimates the relative weights of data for future statistical analysis. The second stage consists of statistical support programs for evaluation of the results of stage 1. The programs used in this phase are: TEATEST, RAT, CORL, REGRESS, DICK, TG DOSE, RANK, and YOUTEST. Our research activities also include procedures to determine weight patterns of patients. The program involved in this aspect is BODYCOMP. 163 Grant No. RROO311-04. Seeticn IV Name: Reitan, J. Project: INDIRECT Department: Anesthesia Project Description: We are processing cardiac internal timings collected by non-invasive, indirect techniques in order to monitor the contractile state of the heart under varying loads and drugs. Name: Rosenberg, 5S. Project: MEDONCOL Department: Medicine-Oncology Project Description: Patient and disease analysis - primarily to correlate drug responsiveness in cancer patients for educational and research purposes. Name: mith, P. Project: PREMIES Department: Pediatrics Project Description: This data will be used in any study involving pre- mature or sick newborn infants cared for in the Stanford nurseries. Such items as birth weight, gestational age, system disease, etc., will be correlated by pairs. 164 Grant No. RROOZ11-04 Section IV Name: Spevack, A. Project: CONDIT Department: Psychiatry Project Description: Classical conditioning experiments of amygdalecto- myed and intact monkeys. Name: Stark, G. Project: CHAOS Department: Biochemistry Project Description: ACME serves two primary functions. First it is used to analyze data generated from steady state kinetic experiments on enzymes, primarily aspartate transcarbamylase from Eschenchia coli. Second, it is used to process chromatograms generated by an amino acid analyzer. It is also used for various research and educational tasks by graduate students and medical students, such as analyzing the sedimentation velocity of proteins in the ultracentrifuge. Many of the kinetic experiments referred to above could not be done with- out the services of ACME, since they involve trial and error fitting of several parameters to complex functions. The routine processing of chromatograms on ACME introduces accuracy and dependability not otherwise available. Name: Stillman, R. Project: PSYGAME Department: Psychiatry Project Description: Our project involves the use of an interactive system for the interviewing and testing of psychiatric patients. We are attempting to use the computer and a peripheral CRI display for anticipated psychological testing. This includes terms from standard psychological tests and novel tests which the computer is especially suited for. 165 Grant No. RROO411-04 Section IV Name: Stocker, B. Project: Stm Department: Medicine - Micro Project Description: Main project concerns genetics and physiology of Salmonella typhimurium - in particular somatic lipopolysaccharide, flagella and motility, and plasmids, especially R and colicine factors. I am co-investigator in Dr. Esther Lederberg's project, which concerns mainly recombination-deficient mutants in the same organism. Main ACME usage has been 1) in statistical analysis of data from experiments concerning mouse pathogenicity of lipopoly- saccharide mutants (estimations of LD50, rate constant for clearance of bacteria from blood stream, harmonic mean times-to-death, sig- nificance tests, etc.) and 2) for storage and analysis of extensive stock-culture data concerning strains with numerous genetic markers. Name: Strickland, R. Project: GASTRIC Department: Medicine - G. I, Division Project Description: I am involved in clinical research projects relating to gastric secretory function tests and have used the ACME Computer Facility over the past year for filing of data collected from these projects and for statistically analyzing the results obtained. 166 Grant No. RROO411-04 Section IV Name: Summerlin, W. Project: BIOCHEM Department: Dermatology Project Deseription: To study biochemical control of collagen formation via proline/hydroxjproline (ratios). Name: Vosti, K. Project: VOSTI Department: Medicine - Infectious Diseases Project Description: Cross-tabulating variables associated with bacterial infections such as underlying disease, age, year, prior and contemporen- eous antibiotics, steroids and immuno-suppressives, appropriateness of treatment, and outcome (survival, death). 167