Ms. Diana
I.
Duran
Los Alamos National Laboratory
Public Affairs Office, CER-20
P. O. Box 1663, MS A104
Los Alamos, NM 87545
Phone: 505-667-1187
Fax: 505-665-7879
E-mail: di@lanl.gov
Number of Human Subjects projects reported: 28
| LANL-52-(91-06) | "Manhattan Project Plutonium Workers Health Study" |
| LANL-98-02 | "Neuromagnetic Mapping of Functional Centers in the Human Brain" |
| LANL-01-07 | "Polarized Elastic Scattering Spectroscopy System" |
| LANL-02-02 | "Application of a High-Geometry, Low-Energy Photon Detector, and Simple Sample Preparation Techniques for Rapid Analysis of Bioassay Samples" |
| LANL-02-10 | "Facilitation and Support for the Design and Testing of a Relevant HIV-1 Vaccine Candidate" |
| LANL-03-04 | "HIV Compartmentalization in Women: Virus and CTL Response" |
| LANL-03-07 | "Use of Nuclear Medicine Patients to Determine the Response of Radiation Detection Systems" |
| LANL-04-01 | "Creation of Antibody or Flurobody Libraries from Uninfected, Infected, or Immunized Persons" |
| LANL-04-05 | "HIV-1 Diversity in Optimized Vaccine Selection " |
| LANL-04-06 | "Understanding the Mechanism of Beryllium-Induced Immune Responses in Health, Individuals, and Patients with CBD/Immunologic Reactivity of Beryllium Species" |
| LANL-04-07 | "Spatiotemporal Imaging of Human Visual System Processing" |
| LANL-04-10 | "HLA Typing and Epitope Mapping Relative to HIV Vaccine Design-Contract #2" |
| LANL-05-01 | "Ultra Low Field Magnetic Resonance Imaging" |
| LANL-05-03 | "Nanocrystal Quantum Dots" |
| LANL-05-04 | "Raman Spectroscopy for the Diagnosis of Cancer in the GI Tract" |
| LANL-06-01 | "Raman Spectroscopy of Cervical Tissue Biopsy Samples" |
| LANL-06-02 | "Center for HIV/AIDS Vaccine Immunology" |
| LANL-06-03 | "Retention of a Diverse Work Force at LANL" |
| LANL-06-04 | "Measures of Semantic Association" |
| LANL-06-05 | "Detection of Tuberculosis Antigens in Patient Urine Using the Optical Biosensor" |
| LANL-06-06 | "Identification of Breast Cancer Markers in Nipple Aspirate Fluid using the Waveguide based Optical Biosensor Developed at LANL" |
| LANL-06-07 | "Comparative Analysis of Endogenous Oxidastive Stress-Induced Responses by Low LET Ionizing Radiation" |
| LANL-07-01 | "Center for HIV/AIDS Vaccine Immunology - Umbrella Study" |
| LANL-07-02 | "Remote Biometrics" |
| LANL-07-03 | "Pilot Study of Mound Radiation Workers" |
| LANL-07-04 | "Nanostructural and Biomechanical Investigation of Enamel, a Natural Nanocomposite" |
| LANL-07-05 | "Global HIV/AIDS Vaccine Enterprise (GHAVE)" |
| LANL-07-06 | "Effect of Glovebox Gloves on Dexterity" |
Other projects of interest associated with this site:
| JHUSHP-07-DE-FC01-06EH06014 | "Development of a Medical Surveillance Program for Former Los Alamos and Sandia National Laboratories" |
| NIOSH-95-004 | "Leukemia Case-Control Study" |
"Manhattan Project Plutonium Workers Health Study"
Principal Investigator: Dr. Laurie D. Wiggs, Los Alamos National Laboratory
Project started in: 1952
Status of the Research this Fiscal Year:
Study is no longer enrolling, but participants still receive research-related interventions (e.g., still receiving treatment, obtaining blood draws), or interactions (surveys, questionnaires).
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 02/08/07
IRB approval number: LANL 91-06
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 12
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Manhattan Project Plutonium Workers Health Study
The study of Manhattan Project Plutonium Workers was begun in 1952 by Louis Hemplemann and Wright Langham. The study identified the 26 Manhattan Project workers who had the highest exposures to plutonium (Pu) at Los Alamos during World War II. The health and estimated plutonium deposition of these workers have been followed at approximately five-year intervals since 1952. At many of these intervals the workers returned to Los Alamos for complete medical and dental exams. Now due to the advanced age of the surviving members of the cohort, travel to Los Alamos is no longer feasible. In addition to other medical/dental examinations, workers have provided urine samples for plutonium dosimetry analyses. These analyses have been used to better estimate the doses of these workers and also to improve the techniques used to monitor plutonium deposition among exposed individuals. The workers have participated in many other projects, such as a chromosome analysis, whole body dosimetry, and other medical and research projects. Mortality follow-up of the cohort has been ongoing from 1952 to the present.
It is now time to update the vital status for the cohort and obtain death certificates for the members of the cohort who have died. We will contact the National Death Index (National Center for Health Statistics) to determine if this federal government service can be used to update the vital status and to obtain the outstanding death certificates. If the National Death Index is not suitable, we will return to the Human Subjects Research Review Board (HSRRB) for approval to trace and locate the cohort members and to collect death certificates.
Once this is complete, we will locate and contact the surviving members of the cohort and obtain updated medical histories and new urine samples. The contact letter, the questionnaire, and the updated informed consents will be provided to the HSRRB for review and approval prior to use.
This updated information on the medical condition of the surviving cohort members will be analyzed and used for an updated publication. Mortality analyses comparing the mortality experience of this cohort with the expected mortality based on U.S. death rates will be conducted and included in the paper(s) describing this study. The individuals will not be identified in this publication.
Urine bioassay samples have historically been collected from the subjects in the Manhattan District workers cohort at Los Alamos National Laboratory (LANL) during the entire period that the study has been ongoing. The latest samples were collected from surviving subjects in the autumn of 2002. These samples were analyzed for plutonium content using either alpha spectrometry or the more sensitive thermal ionization mass spectrometry (TIMS) method. These and previous bioassay samples are being used to estimate the radiation doses for each of the workers in the population.
It is anticipated that additional samples will be collected in the future from the cooperating survivors in this study. This activity will only occur if funding is obtained. In the event we obtain funding, we will request a modification from the HSRRB.
LA-UR-07-7356
"Neuromagnetic Mapping of Functional Centers in the Human Brain"
Principal Investigator: Dr. Robert H. Kraus, Jr., Los Alamos National Laboratory
Project started in: 1998
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Los Alamos National Laboratory
Most recent approval: 01/24/07
IRB approval number: LANL 98-02
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 4
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Study Title: Neuromagnetic Mapping of Functional Centers in the Human Brain
Background - We have completed construction of a novel whole-head superconducting image sensor (SIS) system for magnetoencephalography (MEG) of the human brain. We have recently added new background sensor channels and developed computational algorithms to subtract background in both real time and post-processing. Real time data are presented to the user of this system within a fraction of a second of the actual signal acquisition. The experimental calibration and validation of the system using physical phantoms has demonstrated the best source localization reported to date. We have demonstrated system efficacy by direct comparison with a commercial whole-head MEG array with the same physical phantoms. The Los Alamos MEG system has demonstrated application of new physics principles to virtually eliminate ambient background signals from the brain signals. This system will provide important capabilities for noninvasive functional human brain measurements for both clinical applications and basic research. Current work to combine the MEG with high-density electroencephalography (EEG) will further enhance localizing and understanding brain function. These techniques measure a physical effect of neuronal currents with temporal resolution not limited by sluggish vascular response, unlike positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) that measure hemodynamic changes presumably associated with neuronal activity. High temporal resolution is particularly important for studying neurological disorders such as epilepsy, where temporal information is a major diagnostic, and for fundamental studies of synchronization and oscillatory brain activity.
Objectives - We have recently completed the Los Alamos National Laboratory (LANL) SIS whole-head MEG system and implemented unique background noise rejection hardware and software. The system has demonstrated "noise-free" acquisition of brain signal in 149 primary channels. Simultaneous acquisition of high-density EEG data is being acquired to demonstrate the value of combining magnetic and electrical data to improve the accuracy and reliability of source localization of brain activity. The primary objective continues to be demonstrating efficacy and improving performance for this new instrument. Human studies were performed to obtain representative data for the new SIS MEG system. The focus through FY2006 was to obtain temporal data for well known and thoroughly investigated paradigms to demonstrate improved signal quality and source localization. The most simple evoked response experiments were performed (for example, somatosensory and auditory response paradigms) to evoke a primary somatosensory cortex and primary auditory response. These data were compared to well known, time-domain responses for healthy subjects to confirm the outstanding temporal and signal-to-noise performance of the new instrument.
Methodology - Since the focus of the experiment was determining system response based on well known neurological responses, the methodology was very simple median nerve stimulation intermixed with a simple auditory "click." The data in and around the N20 and P100 to P150 responses were examined and compared to data from prior investigators for temporal response and general location. In addition, the relative locations of somatosensory response were correlated with the location of the auditory response (primary auditory cortex). We reported recording brain signals that had no residual ambient noise in the resulting "de-noised" signal. This experiment is completely non-invasive and involves absolutely no use of ionizing radiation, chemicals, or biological substances. In the future, different evoked response experimental paradigms that have been long established in functional brain research will be used. These paradigms include auditory, visual evoked response, somatosensory, and motor paradigms. Auditory stimuli include simple "clicks" presented at a low but audible level. Finally, motor paradigms include finger tapping using one or multiple fingers, "knocking" (wrist motion), toe tapping, etc. Although more complex paradigms (such as facial patterns) have been studied, the complexity of these evoked responses is such that they are unlikely to be used to test system efficacy. Specific paradigms are developed in collaboration with neuroscientists at LANL and the University of California, San Diego, Radiology Department.
Experiments in FY2006 focused on signal quality improvement by noise rejection methods, comparing features of signal-to-noise and temporal details of the signal, and localization reliability and accuracy by combining MEG and EEG. The evoked responses for the paradigms noted above have been extensively studied and typical signal amplitude fluctuations and temporal features of the various responses are reproducible. We have developed methods to acquire virtually noise-free brain signal by MEG and EEG alike.
Involvement of Human Subjects - Human subjects involved were researchers involved in the technical aspects of the project or related projects. All were not only well apprised of the procedure, but have been either directly involved in designing and carrying out the experimental design or working on closely related efforts. Each subject read and signed the consent form. Confidentiality is preserved by keeping any linkage between subject and data in a locked administrative vault.
Outcome - We have found preliminary results of the noise-free MEG and combined MEG-EEG source localization very exciting. A new major National Institutes of Health (NIH) grant has been submitted to extend this work with collaborators from the University of Oregon, the University of Washington, Seattle, and Electrical Geodesics, Inc. This proposal is currently under review. Noise rejection dramatically improved the quality of the LANL SIS-MEG data. Real time algorithms to provide researchers (and ultimately clinicians) the opportunity to review data while the subject is being examined are progressing well.
LA-UR-07-7356
"Polarized Elastic Scattering Spectroscopy System"
Principal Investigator: Dr. Judith R. Mourant, Los Alamos National Laboratory
Project started in: 2001
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 11/28/06
IRB approval number: LANL 00-07
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 20
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Polarized Elastic Scattering Spectroscopy System
Objectives: The aim of this study is to test a new technology to diagnose cervical cancer. Although current methods of screening for cervical cancer have made a huge impact on the prevalence of cervical cancer, the current methods have some significant drawbacks. The current tests are not very accurate - at a recent presentation by a National Institutes of Health (NIH) program manager the sensitivity and specificity of the Pap smear were both given as about 50 percent. Secondly, there is a delay in finding out the results of a Pap smear. This delay in addition to the fact that a portion of the population frequently does not return for follow-up means that some people do not get treatment. We are developing a non-invasive optical technique that we hope will reduce the first problem and eliminate the second.
Methodology: A fiber optic probe is placed in contact with the tissue. Light passes down the probe through a polarizer that is part of the probe into the tissue where it is scattered. Some of the light returns to the tissue surface, this light is collected with information about its location and polarization. The intensity and wavelength dependence of the collected light provides information about the tissue structure on the scale of microns and smaller.
Risk: There is no exposure to ionizing radiation, radioactive substances, or chemical substances. The protocol and specifics of the instrumentation of this study have been reviewed by the Food and Drug Administration (FDA), and the FDA has found that the proposed clinical investigation is a nonsignificant risk device. There are no known risks or side effects related to the light probe. The most common side effects of cervical biopsy include anxiety, minimal cramping, pain from bleeding during the biopsy, and vaginal spotting afterwards.
Involvement of human subjects: In order to participate in the study, patients will have to sign a consent form. This consent form describes, the purpose and background, the procedures, possible risks and discomforts, benefits of participation, and confidentiality of the study. The following information was taken from the consent form. A slender fiber optics tube will be placed against the surface of the cervix while the light-reading device processes the light scattering from cervical tissue. A small piece of tissue will then be removed to be analyzed by a pathologist. The findings of the pathologist will be used to determine the sensitivity and accuracy of the light-reading process. Tissue will be stored for future testing. At this time it has not been determined what these further tests may be; however, all testing of the tissue will relate directly to this study. Once the study is no longer acquiring information, the tissue will be discarded. Only study personnel and oversight committees will have access to study information which will be kept in a secure area. Patient/participant names will not be used in any publications.
At this stage in the study, the expected results are an understanding of the reproducibility of the measurement system and preliminary correlations with pathology. These results will be used to improve our experimental measurement system and the study design. The criterion for success or failure for the study is ultimately the correlation with pathology. If sensitivities and specificities of 85 percent or higher are obtained, the study will be a success. If lower specificities and sensitivities are obtained, then the study will either have to be terminated or redesigned.
LA-UR-07-7356
"Application of a High-Geometry, Low-Energy Photon Detector, and Simple Sample Preparation Techniques for Rapid Analysis of Bioassay Samples"
Principal Investigator: Dr. Raymond A. Guilmette, Los Alamos National Laboratory
Project started in: 2002
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 02/14/06
IRB approval number: LANL 02-02
Explanation of IRB approval:
Study was closed in FY2007. No approval was required.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Application of a High-Geometry, Low-Energy Photon Detector, and Simple Sample Preparation Techniques for Rapid Analysis of Bioassay Samples
This study was closed in FY2007.
LA-UR-07-7356
"Facilitation and Support for the Design and Testing of a Relevant HIV-1 Vaccine Candidate"
Principal Investigator: Dr. Bette T. Korber, Los Alamos National Laboratory
Project started in: 2002
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 09/30/06
IRB approval number: LANL 02-10
Explanation of IRB approval:
Study is closed. No funding available.
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston, Mass.
Most recent approval: 09/29/06
IRB approval number: MGH: 2001-P-001941
Explanation of additional approval:
Study is closed.
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston Mass.
Most recent approval: 10/05/05
IRB approval number: 2001-P-000012
Explanation of additional approval:
Study is closed.
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston Mass.
Most recent approval: 10/15/05
IRB approval number: 2002-P-000063
Explanation of additional approval:
Study is closed.
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital, Boston Mass.
Most recent approval: 09/19/06
IRB approval number: 2002-P-000132
Explanation of additional approval:
Study is closed.
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston, Mass.
Most recent approval: 07/14/06
IRB approval number: MGH: 2004-P-001730
Explanation of additional approval:
Study is closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 400
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Facilitation and Support for the Design and Testing of a Relevant HIV-1 Vaccine Candidate
This is a study of human immunodeficiency virus (HIV) immune responses in populations with differences in host immune genes and differences in the infecting virus. The National Institutes of Health (NIH) funded this contract to explore the host immune response to HIV in populations that are likely vaccine sites. The baseline information will help both in the design of optimal vaccines for particular populations and in the interpretation of vaccine trial immunogenicity results.
Whereas Europe and America have mainly HIV-1 subtype B, eastern Africa has predominantly subtypes A and D. Southern Africa on the other hand has mostly subtype C. Because of this viral variation, and differences in highly variable, immunologically important human genes in different regions of the world, a vaccine that is best for one location might not be optimal for another.
We do not do any experimental work in the Theoretical Division at Los Alamos. The National Institutes of Health (NIH) specified that the basic immunological information gained through this contract will be incorporated into the NIH-DOE sponsored database at Los Alamos to facilitate HIV vaccine design in the developing world. Part of our task is to make the appropriate information concerning the immunologically reactive parts of the virus in the Barbados, and in South Africa, available to HIV researchers through our Los Alamos National Laboratory (LANL)-based HIV immunology database. Prior to public release of the data, we will work with our co-authors and assist them in analyzing the data and writing the publication, then the published data will be made available to other researchers.
Blood is drawn from HIV positive patients attending participating clinical locations in the U.S., South Africa, and Barbados. Patients are asked if they would mind giving a blood sample to be used for the research study; this work may help to design an HIV vaccine and appropriate tests for vaccine trials in the region. Local IRB-approved consent forms are used; copies of the consent forms and the initial IRB approvals were provided to the LANL/DOE IRB when the project was approved. There is no direct benefit to the patient, only possible benefit to their community and society. The patient is already attending the clinic and is known to be HIV positive. Technology transfer is bringing immunology assays to South Africa and Barbados, and immunological testing is done on site. A small amount of the blood sample is shipped to Harvard University and to the University of Washington. Host immune response genes are characterized, the viral sequence is obtained, the amount of virus in the sample is measured, and the immune response is measured. Viruses may be cultured or cells may be cultured for testing the immune response on site or at Harvard.
Minimal clinical records accompany the samples, essentially just the CD4 T-cell count, viral load, and treatment status. The patient is given a coded identifier for the purpose of the study and communication between investigators. Only the patient's physician has access to the code. The kind of data we are collecting is often found in scientific publications. The patient is being treated for being HIV positive, and this study does not compromise treatment or privacy. The primary risk involved is associated with the blood draw, and patients are fully informed concerning the research nature of the study. Their treatment is not influenced in any way by their choice to participate or not.
LA-UR-07-7356
"HIV Compartmentalization in Women: Virus and CTL Response"
Principal Investigator: Dr. Carla L. Kuiken, Los Alamos National Laboratory
Project started in: 2003
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 02/13/06
IRB approval number: LANL 03-04
Explanation of IRB approval:
Study is closed.
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: State of New York Department of Health
Most recent approval: 06/22/06
IRB approval number: 00-312
Explanation of additional approval:
Study is closed.
Type of Review:
Expedited
Approving Institution: SUNY Downstate Medical Center, Brooklyn NY
Most recent approval: 01/13/06
IRB approval number: 04-029
Explanation of additional approval:
Study is closed.
Type of Review:
Expedited
Approving Institution: SUNY Downstate Medical Center, Brooklyn NY
Most recent approval: 02/24/06
IRB approval number: 90-129
Explanation of additional approval:
Study is closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 20
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: HIV Compartmentalization in Women: Virus and CTL Response
CTL - Cytotoxic T lymphocyte
a. Objectives: The objectives are to characterize the extent of differences between human immunodeficiency virus (HIV) variants found in the blood and genital tract of women and to investigate the role of the immune system in driving these differences.
b. Methodology: Women displaying differences between virus found in the blood and that from the genital tract will be identified. The role of the host immune response will be investigated by characterizing the ability of immune cells to recognize variants from the two compartments.
c. Risk: Not applicable.
d. Involvement of Human Subjects: Samples will be obtained from the two compartments, and the virus found will be characterized using sequencing of the pol and env genes. The risk is pain and possibility of infection from the blood draw. All women are seen within the framework of a larger cohort study and their privacy is guaranteed. They are asked to sign an informed consent form prior to participating in the study.
e. Anticipated results: We expect to be able to draw definite conclusions about the relationship between immunological pressure and the existence and nature of compartment-specific variation in HIV. The study will be terminated when sufficient samples have been obtained to draw these conclusions.
Study is closed.
LA-UR-07-7356
"Use of Nuclear Medicine Patients to Determine the Response of Radiation Detection Systems"
Principal Investigator: Mr. Brian G. Rees, Los Alamos National Laboratory
Project started in: 2003
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 01/08/06
IRB approval number: LANL 03-07
Explanation of IRB approval:
Study is closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Use of Nuclear Medicine Patients to Determine the Response of Radiation Detection Systems
Radiation detection systems are being installed at large numbers of locations to detect the illicit movement of radioactive materials. These detection systems routinely detect patients that have recently received nuclear medicine treatments. There is considerable interest in obtaining detailed radiation detection data from patients who receive nuclear medicine treatments. Typically patients that are detected by a system are released as soon as practicable after the source of the radiation is confirmed. Follow-on measurements are not sought due to the operational nature of the installation. It is not practicable from a number of perspectives to administer radiopharmaceuticals to people in order to conduct measurements.
Los Alamos National Laboratory (LANL) employee volunteers will be solicited at the nuclear medicine department of local hospitals or other suitable locations by the use of information that will be provided to them after administration of treatment. Their medical conditions will not be solicited; however, they will be requested to provide information on the nuclide, time of administration, activity at administration, and chemical formulation. Their individual identification number or name will not be recorded on measurement data sheets or associated with the measurements. Additional information asked of the volunteers will include any voiding since the administration of radioisotopes by the subject's primary care physician, as well as the subject's age, weight, height, and gender. Volunteers will be placed at various distances and angles from fixed and portable radiation detectors and may be asked if they can walk or drive (government vehicles) near fixed or portable instruments.
In addition to the measurements that could be conducted, this is an opportunity to ensure patients are aware of their responsibilities regarding thermoluminescent dosimeters (TLDs), etc.
Risks: There are no risks imposed on people by their participation in this study. Any measurements in the presence of other radioactive material will be conducted in such a manner as to result in less than 5 mrem from the additional material so that a TLD will not be required for the patient. All personnel conducting measurements will wear TLDs.
Benefits: The response of radiation detection instruments to people with nuclear medicine treatments will be better understood. This will improve the ability to detect illicit movement of radioactive materials and possibly minimize the unnecessary delay of nuclear medicine patients in locations with radiation detection systems.
Study is closed.
LAUR-07-7356
"Creation of Antibody or Flurobody Libraries from Uninfected, Infected, or Immunized Persons"
Principal Investigator: Dr. Andrew M. Bradbury, Los Alamos National Laboratory
Project started in: 2004
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 10/27/06
IRB approval number: LANL 04-01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 76
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Title: Creation of Antibody or Flurobody Libraries from Uninfected, Infected, or Immunized Persons
This study outlines the use of human blood samples from normal, immunized, or infected individuals for the generation of libraries of antibody genes. In the case that the blood is from either infected or immunized individuals, the libraries created will be enriched in high affinity human antibodies recognizing either the immunogen or the infectious organism. Blood from non-immunized/infected individuals would not contain the enhanced high affinity repertoire of antibodies found in immunized/infected individuals, although they will provide a source of lower affinity antibodies against a broad range of different targets. Human subjects are used for such studies, as most information is available on human antibody genes, and derived antibodies have the potential to be used for therapeutics. There is no risk to subjects, phlebotomy (the taking of blood) being a widely used non-hazardous operation. The samples used are anonymous and pooled. As this is a procedure in which we anticipate using different infectious organisms and will be identical whatever the infectious organism, we would like to put in place general Institutional Review Board (IRB) and Institutional Biosafety Committee (IBC) approvals which would permit us to inform these committees of any new infectious organisms which are planned without having to resubmit essentially identical proposals.
LAUR-07-7356
"HIV-1 Diversity in Optimized Vaccine Selection"
Principal Investigator: Dr. Karina Yusim, Los Alamos National Laboratory
Project started in: 2004
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 02/23/06
IRB approval number: LANL 04-05
Explanation of IRB approval:
Study moved to exempt status.
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital
Most recent approval: 09/30/06
IRB approval number: 2001-P-001941/9
Explanation of additional approval:
Study is now exempt.
Type of Review:
Expedited
Approving Institution: Mass. Dept. of Public Health, Lemuel Shattuck Hospital
Most recent approval: 09/16/06
IRB approval number: 05-PARC011
Explanation of additional approval:
Study is now exempt.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 20
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: HIV-1 Diversity I Optimized Vaccine Selection
The extraordinary scale of human immunodeficiency virus (HIV) variation poses a major obstacle for acquired immune deficiency syndrome (AIDS) vaccine development. The HIV Database in Los Alamos National Laboratory (LANL) now contains more than 80,000 unique HIV strains. Such extraordinary variability hampers very seriously the effort to develop an effective vaccine against HIV/AIDS. The major goal of this study is to integrate all HIV sequence and immunological information publicly available to date and optimize protective immunity of the candidate AIDS vaccine. As a first step, we are working on integrating computationally all publicly available information stored in the Los Alamos HIV Database and studying through HIV genome position by position to select amino acids for the vaccine in the highly variable positions of the HIV genome, that would optimize potential immune response of the vaccine target population. In particular, we are working on computationally predicting peptides that potentially can induce the highest immune response in the vaccine target population.
This study does not include any ionizing radiation, radioactive substances, chemical substances, or exposure to any chemical or radioactive substances or ionizing radiation.
Study moved to exempt status
LAUR-07-7356
"Understanding the Mechanism of Beryllium-Induced Immune Responses in Health, Individuals, and Patients with CBD/Immunologic Reactivity of Beryllium Species"
Principal Investigator: Dr. Goutam Gupta, Los Alamos National Laboratory
Project started in: 2004
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 05/20/06
IRB approval number: LANL 04-06
Explanation of IRB approval:
Study is closed.
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: Central Beryllium IRB
Most recent approval: 05/19/06
IRB approval number: CBeIRB(04)-19
Explanation of additional approval:
Study is closed.
Type of Review:
Expedited
Approving Institution: University of Pennsylvania
Most recent approval: 01/07/06
IRB approval number: 800836
Explanation of additional approval:
Study is closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 5
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Title: Understanding the Mechanism of Beryllium-Induced Immune Responses in Health, Individuals, and Patients with CBD/Immunologic Reactivity of Beryllium Species
The possible risk of Chronic Beryllium Disease (CBD) from beryllium (Be) exposure in Los Alamos National Laboratory (LANL) and other defense laboratory workers mandates that we formulate safety guidelines by understanding the responses of the human immune system due to Be exposure. Beryllium causes hyperproliferation of T cells in genetically susceptible CBD individuals. The susceptibility is mapped to the Multiple Histocompatibility Complex (MHC) class II receptors on the antigen presenting cells. The main goal of this project is to characterize the Be-sensitive genes and proteins belonging to proliferative and anti-proliferative pathways and then determine their functions in immune cells from normal and CBD individuals.
The project is designed in such a way that we would only need the blood samples from the CBD patients during the last phase of our research. We will take blood samples from CBD patients only after we identified a small set of putative disease markers based on our thorough investigation using our primary cell model derived from the commercial source of blood from healthy donors.
From each site, we will recruit three to six individuals with CBD. We expect that 25 to 35 ml of whole blood from each individual will be sufficient to obtain 50 to 100 million Peripheral Blood Mononuclear Cells (PBMCs) and 2 to 5 million Dendritic Cells (DCs). Whole blood will be collected in a bag or tube that contains the appropriate volume of anticoagulant to prevent clotting and maintain cell viability. Blood components will be separated by centrifugation. The specific gravity ranges for red cells (1.08 to 1.09), platelets (1.03 to 1.04), and plasma (1.023) are sufficiently different to enable isolation by centrifugation. The white cell fraction (buffy coat) has an intermediate density between red cells and platelets and will be contaminated with both cell types. To separate out the PBMCs and DCs, density gradient centrifugation using ficoll-hypaque applied to the buffy coat fraction will remove the red blood cells, platelets, and granulocytes. The recovered cells will be used in different cellular assays, including cytokine release, microarray, and proteomics analysis. These data will be compared with the results from similar experiments with healthy donors. Cytokine release will be assayed by Enzyme-Linked-Immunosorbent Assay (ELISA). For microarray or proteomic analyses, cells will be lysed, ribonucleic acid (RNA) or protein extracts will be isolated respectively, and then applied to either an in-house glass slide array set-up or 2D gel electrophoresis and subsequent mass spectroscopy. Following cell lysis, the RNA and protein extracts can be moved to Biosafety Level l (BSL1) facilities for further work. Quality control of cell lysates will include filtering to remove any bacteria or viruses that may be present in the cell preparation.
The risk of this project is low given that work will be performed under BSL2 conditions. We will follow procedures as stated for work with human bloodborne pathogens, and all workers have received this training prior to start of work.
PBMCs derived from human subjects are coded, but no individual information (name, social security number, address, telephone number, or any other direct personal identifier) is given to LANL.
Study is closed.
LAUR-07-7356
"Spatiotemporal Imaging of Human Visual System Processing"
Principal Investigator: Dr. John S. George, Los Alamos National Laboratory
Project started in: 2004
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 05/20/06
IRB approval number: LANL 04-07
Explanation of IRB approval:
Study is closed.
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital, Boston, Mass.
Most recent approval: 10/24/05
IRB approval number: 1999-P-010946/27
Explanation of additional approval:
Study is closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Spatiotemporal Imaging of Human Visual System Processing
a. Objectives: The objectives of this project are to further develop and apply experimental and analytical techniques for dynamic imaging of human brain function. The approach involves the integration of anatomical and functional magnetic resonance imaging (fMRI) which provides information on brain anatomy, connectivity (wiring), and localization of function, together with magnetoencephalography (MEG) and electroencephalography (EEG), which provide information on the large-scale dynamics of brain function. In addition to continuing technical development, the work will develop new methods for brain modeling incorporating information on brain connectivity and will begin to more aggressively apply these methods to study the processing of visual information in the human brain.
b. Methodology: Experimental procedures employed at Massachusetts General Hospital (MGH) include anatomical and functional MRI, MEG, and EEG. These techniques are non-invasive and entail minimal risk. The activities performed at Los Alamos National Laboratory (LANL) involve computational analysis and modeling intended to localize sources of neural activity and to describe the dynamics of activation.
c. Ionizing radiation, radioactive substances, or chemical substances: Human subjects are not exposed to any ionizing radiation, radioactive substances, or chemical substances.
d. Involvement of human subjects:
1. Procedures involving human subjects: Experimental data will be collected at facilities of the Martinos Imaging Center at MGH, under protocols reviewed and approved by the institution. The LANL contribution to this project is to develop, evaluate, and apply computational models of the physical processes that give rise to MEG and EEG signals at the head surface. This will include boundary-element and finite-difference calculations that incorporate data from human MRI studies. We may also analyze MEG and EEG data collected in these studies.
2. Potential risk: The activities performed at LANL involve computational analysis and modeling and pose no risk except for the potential to identify study participants.
3. Privacy/confidentiality/consent issues: All of the experimental data used at LANL are cataloged by the project principal investigator (PI) so that subjects cannot be identified, directly or through identifiers linked to the subject. Analysis and modeling procedures will not generate personally identifiable tags. We acknowledge the potential concern that volumetric MRI data might be used to generate a recognizable rendering of the research subject. Solutions to this problem are presently being studied by the National Institutes of Health sponsored BioInformatic Research Network (BIRN) on structural anatomy, as well as working groups in the Human Brain Project and elsewhere. As an interim measure, no realistic renderings or complete image datasets will be stored on publicly accessible databases, and technical solutions to prevent identification of individuals will be adopted as they become available.
e. Results: These studies are intended to develop methods for integration of multiple imaging modalities, applicable to a wide range of functional neuroimaging studies. In addition to the immediate application to basic neuroscience studies (of human visual processing in this case), these studies will have applications in neurology, mental health, and other areas of human brain science. Current term of the project is four years, but we anticipate application for future funding to address new issues raised by this work.
Study is closed.
LAUR-07-7356
"HLA Typing and Epitope Mapping Relative to HIV Vaccine Design-Contract #2"
Principal Investigator: Dr. Thomas K. Leitner, Los Alamos National Laboratory
Project started in: 2004
This is an international project.
Foreign Subjects Yes
Foreign Data Yes
Foreign Specimens Yes
Foreign Collaborators Yes
Foreign IRB No
Status of the Research this Fiscal Year:
Project funded, but no participants have been enrolled to date.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 09/29/07
IRB approval number: LANL 04-10
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital
Most recent approval: 09/29/06
IRB approval number: 2003-P-001990/1
Explanation of additional approval:
Valid through 9/2008
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Title: HLA Typing and Epitope Mapping Relative to HIV Vaccine Design-Contract #2
Objectives: Increasing evidence indicates an effective HIV-1 vaccine will need to induce strong, cross-reactive antiviral CTL activity and adequate T-helper cell responses as well as neutralizing antibodies against HIV-1. Therefore, this study will identify viral targets of the cellular T-cell responses, as well as characterize the neutralizing antibody responses in the context of extensive viral sequence variability.
Methodology: Blood samples will be collected from individuals in the USA, China, Thailand, and Peru. The individual's immune response to circulating HIV-1 forms will be measured by classifying each individual's immune system (HLA) and measuring specific responses to peptide libraries designed from the HIV-1 forms that circulate in the different geographic regions. Antibody responses will be determined from serum activity to contemporary panels of viral isolates. The actual HIV-1 forms that have infected the individuals will also be determined by DNA sequencing. Statistical analyses will be used to evaluate and find important epitopes that should be included in a HIV-1 vaccine.
Ionizing radiation, radioactive substances, chemical substances: Subjects will not be exposed to any such substances.
Involvement of human subjects:
1) A total of 1,850 HIV infected subjects will be enrolled in the USA, China, Thailand, and Peru. The individuals will be offered to join the study by their physicians and be allowed to enroll after informed consent has been given. Some patients will give more than one blood sample. From some samples cell lines will be established to facilitate testing of antibodies.
2) Blood is drawn at normal visits to the patient's physician. A bruise and/or bleeding at the needle site may occur.
3) All samples will be labeled using an anonymous code. Laboratory personnel and scientists, including those at Los Alamos National Laboratory (LANL), have no way of decoding. All procedures that involve the patient's blood have been approved by the patient, including freezing of the blood, creating cell lines, and using laboratory information. Whether patients participate or not will have no effect on their treatment.
Glossary:
Antibody - Immune molecule that recognizes specific non-human substances
CTL - Cytotoxic T lymphocyte, a white blood cell involved in immune functions
DNA - Genetic material that encodes instructions on how proteins are made
Epitope - Protein segment recognized by immune functions of potential interest for vaccine design
HIV - Human immunodeficiency virus
HLA - Human leukocyte antigen, a molecule that determines what belongs to a person's own body
Peptide - A short chain of amino acids, i.e., a small piece of a protein
T-cell - White blood cell involved in immune functions
LAUR-07-7356
"Ultra Low Field Magnetic Resonance Imaging"
Principal Investigator: Dr. Robert H. Kraus, Jr., Los Alamos National Laboratory
Project started in: 2005
Status of the Research this Fiscal Year:
Recruitment and/or enrollment of new participants or review of records/specimens continue.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Full Board
Approving Institution: Los Alamos National Laboratory
Most recent approval: 01/24/07
IRB approval number: LANL 05-01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 4
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
1. Background and Objectives: Clinical magnetic resonance imaging (MRI) uses strong magnetic fields (on the order of Teslas), to generate images of the brain, body, etc. The high fields are used to align the spins of hydrogen protons into measurable signals. Gradient magnetic fields are used to spatially encode the nuclear magnetic resonance (NMR) signal which is the basis for generating MRI images. We are investigating if low (milliTesla) and ultra-low (microTesla) magnetic fields can be used with ultra-sensitive magnetometers to image anatomical features. Ultra-low fields (ULF) can offer new insights into tissue and material properties not observable at high field strength and are not effected by or detrimental to metal or other materials in subjects (such as medical implants). The use of ultra-low magnetic fields also allows the simultaneous measurement of magnetic fields generated by the human body, e.g., magnetoencephalography (MEG), potentially enabling a single instrument to measure both the anatomical and functional information from a subject.
We will demonstrate that ULF NMR/MRI is possible with human tissue using our instruments and expertise. ULF NMR may also reveal new possibilities in tissue discrimination through our studies of the relaxation times of proton densities at ultra-low fields. We will show that the technology can be adapted to allow simultaneous ULF NMR/MRI and MEG measurements. We will research whether or not the electrical activity of the body directly affects the NMR signal, which would allow a major advance in the localization of the functional activity of the body.
2. Methodology: Our ultra-sensitive magnetometers rely on superconducting quantum interference device (SQUID) technology. The magnetic sensors are completely passive, measuring the signals in the body that are both a result of this switching and of the normal biological electrical activity. Coils of insulated wire will be placed around the subject from which the NMR signals are to be measured. One set of coils will generate the prepolarizing field (<100 milliTesla). Other sets of coils will generate the measurement fields, around 100 microTesla. After the prepolarizing field is switched off, the SQUIDs operate in a normal sensor mode to measure the NMR signals. The switching rates of the magnetic fields (known as "dB/dt") will be below federal and industrial standards.
Subjects may be asked to have a 'typical' clinical MRI for comparison purposes. Anatomical measurements require the subject to remain passive while the NMR signal is measured. We will also measure standard neurological responses based on well known neurological responses. The methodology will be essentially identical to our existing protocol covered under LANL IRB No. 98 LANL 02, "Neuromagnetic mapping of the functional centers in the human brain" using typical median nerve, auditory, and visual stimuli.
3. Ionizing radiation: No ionizing radiation of any kind is used in this study.
4. Involvement of Human Subjects/Risks/Benefits: Human subjects involved will mostly be researchers involved in the technical aspects of the project, as listed at the introduction. All are not only well apprised of the procedure but involved in the designing and carrying out the experimental design. Each subject has read and signed a consent form. Although specific subject identification will be unnecessary, we will encrypt subject identifiers in the data file header to correlate MEG and electroencephalography (EEG) data with MRIs.
Even though this work is designed to be safe for subjects with metal and/or medical implants, people with such implants will not be eligible as study subjects. There are no known risks of MRI measurements except for the potential discomfort of sitting or lying still for the duration of the scan, and a small chance that the subject might experience claustrophobia. Subjects are in continuous communication with the operators and can ask that the scan be stopped at any time.
The magnetic fields used in our study are at least ten times weaker (typically 100 times weaker) than those used in clinical settings. dB/dt values will be at most about 30 percent of (typically much less than) the maximum recommended by MRI industry standards. At our lower field strengths, it is extremely unlikely that a subject will hear any sounds or perceive magnetic field-induced visual effects. Again, the subject may halt the experiment at any time and for any reason.
The results of our study may increase scientific knowledge about anatomy using a technology different from today's clinical MRI machines. There are no benefits to the subject, neither financial nor medical.
LAUR-07-7356
"Nanocrystal Quantum Dots"
Principal Investigator: Dr. Jennifer A. Hollingsworth, Los Alamos National Laboratory
Project started in: 2005
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 03/08/06
IRB approval number: LANL 05-03
Explanation of IRB approval:
Study was approved on 3/8/06 for a period of one year. It was not renewed at that time and is considered closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 2
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Nanocrystal Quantum Dots
The experiment that we need to perform entails shining an infrared light source on a subject and taking a picture of that subject under such illumination. The subject would be the experimenter him- or herself, or a coworker on the project, i.e., no outside subjects. The light sources we have are of two types. One is simply a PAR 56 stage light that we filter to remove the visible-light component, leaving an infrared "white light." The second is also a commercial light. It is a light emitting diode (LED) infrared light used for nighttime surveillance purposes, as well as by hunters, etc. to invisibly (i.e., infrared, not visible light) illuminate an outdoor area. We have three LED sources, (1) the ~940 nm (Cantronic Systems, Inc. Model CSI-IR30m30N; 3,750 mW/SR), (2) the 880 nm (Photon Light Infrared keychain micro light "rated at 11 mW"), and (3) the Photon Freedom Fusion flashlight rated at 66 mW.
Possible risks include the potential for eye damage from the infrared light sources. Based on our reading of the document, "International Programme on Chemical Safety, Environment Health Criteria 23, Lasers and Optical Radiation" by IPCS INCHEM [1982] ( http://www.inchem.org/documents/ehc/ehc/ehc23.htm), we tentatively conclude the following: Exposure, especially brief exposure, to the stage lamp should not pose an eye hazard. The source is broad-band, non-coherent, extended (i.e., not a point source), with a limited output power. Similarly, the LED sources are non-coherent, extended, with a limited output power. Further, the Photon Light keychain light contains one LED at 11 mW power out, while its companion flashlight model contains 6 IR LEDs for an approximate total of 6 x 11 mW, or 66 mW. The Cantronic Systems lamp is 3,750 mW/SR. As discussed below, the exposure limit (EL) for IR-A light (i.e., 700 to 1,400 nm light) is not met.
Specifically, we compare the power values associated with each LED light source to the "Exposure limits for viewing a diffuse reflection of a laser beam or an extended source laser" found in the IPCS INCHEM document (11.8.1, Table 8). (We use this table for EL because, according to the document, no widely accepted limits exist for the infrared spectral region for non-laser sources; we consider the laser-based numbers to be conservative estimates for our non-laser light.) The value found in Table 8 for exposure times from 1,000 to 30,000 seconds (substantially longer than our typical exposure times of 120 seconds or less) for IR-A light is 640 x CA mW/(cm2 x SR), where CA is a wavelength-dependent constant. At 940 nm, the EL is 1,930 mW/(cm2 x SR), and at 880 nm it is 1,470 mW/(cm2 x SR). By assuming a very conservative dispersion angle of 5 degrees (~0.10 SR) and a subject-to-lamp distance of 1 m (100 cm), we determine that the micro LED source exposure would be 0.011 mW/(cm2 x SR). Using the same assumptions, we likewise determine the exposure for the Photon Freedom Fusion flashlight to be 0.066 mW/(cm2 x SR). Similarly, that for the Cantronics Systems lamp is 0.375 mW/(cm2 x SR). Thus, even this highest exposure is >5,000 times less than its corresponding EL. Further, the lamps will be placed above and/or to the side of the subject, i.e., the subject will not be looking directly into the lamp.
Note: Heat stress due to thermal load is not considered here as the light source is either a commercially used stage lamp (with brief exposure time) or an LED source with a known wavelength less than 1,400 nm.
Note: Infrared light sources other than the specific ones described above can be used in the experiments without prompting additional review by the Human Subjects Research Review Board (HSRRB) as long as the source is determined to fall into the safety envelope presented in this abstract. In other words, the resultant exposure caused by any new lamps will be calculated and compared to the reported exposure limits. No lamp will be used that exceeds the EL or approaches it within a factor of 10.
LAUR-07-7356
"Raman Spectroscopy for the Diagnosis of Cancer in the GI Tract"
Principal Investigator: Dr. Judith R. Mourant, Los Alamos National Laboratory
Project started in: 2005
Status of the Research this Fiscal Year:
Study enrollment is permanently closed, participants have completed research-related interventions, and long-term follow-up is completed. The remaining research activities are limited only to data analysis.
Funding for Human Subjects Research:
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 09/29/07
IRB approval number: LANL 05-04
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: Western IRB for Swedish Health Services/Seattle Gastroenterology Associates
Most recent approval: 08/11/06
IRB approval number: 1069720
Explanation of additional approval:
Study is closed. Working on final data anaysis only.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Study Title: Raman Spectroscopy for the Diagnosis of Cancer in the GI Tract
Objectives: The purpose of the study is to (goal #1) obtain Raman spectra of biopsy samples of esophageal tissue, to determine whether relative amounts of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), glycogen, protein, and lipid in the esophageal tissues can be accurately measured, and (goal #2) determine if this information can be used for diagnosis of cancers and pre-cancers.
To determine the success of goal #1 (determining whether Raman spectroscopy can be used to identify gross biochemical composition of the tissue), the following questions must be addressed: Are the residuals of the fits of spectral data to biochemical components similar (e.g., within a factor of two) to the residuals that were obtained in recent published work on cells? And are the results that are obtained for biochemical composition similar to values published in the literature? The success of goal #2 (determining whether Raman spectroscopy is useful for diagnostics) will be evaluated by determining if there is a correlation between changes in the Raman spectra and changes in pathology.
Methodology: A new Raman spectroscopy device will be tested on the biopsy specimens of subjects who are undergoing routine endoscopic surveillance of Barrett's esophagus or staging of esophageal cancer. Participants will have agreed to have their esophageal biopsy specimens, which have been acquired with ordinary pinch biopsy forceps, measured with the Raman devise just prior to placing the specimens in a container of formalin. There will be no Raman measurements on the patient/human subject. The Raman spectroscopy device will be in contact with the biopsy only after the specimen has been removed from the body.
Human Subject Participation: A list of patients who have relatively long segments of columnar epithelium in the esophagus (i.e., patients who have serious cases of Barrett's esophagus), and patients being treated for esophageal cancer, undergoing repeat staging, will be contacted to schedule routine reevaluation. At this time, the patients will be informed of the study and asked if they wish to participate. Researchers plan to enroll 25 patients for the study and participants will be required to sign a consent form and be given an opportunity to ask questions prior to participation.
The only potential risks to the patients are damage to the biopsy specimen by the Raman laser and the fact that there will be a class IIIb laser in the examination room. An assessment of the possibility of damage to the biopsy specimen has been examined in depth. The conclusion is that the laser will not damage the biopsy specimen. Engineering controls will be used to assure that the class IIIb laser is not an eye hazard to anyone.
In order to compare the Raman spectra to pathology results, researchers at Swedish Medical Center, Seattle, WA must have access to identified medical records. A code will be used in all communications between Swedish Medical Center and Los Alamos National Laboratory (LANL) to prevent sending Public Health Information (PHI) to LANL. LANL personnel will be present at the medical examination/procedure (to operate the Raman spectroscopy equipment) and therefore may have incidental access to PHI.
LAUR-07-7356
"Raman Spectroscopy of Cervical Tissue Biopsy Samples"
Principal Investigator: Dr. Judith R. Mourant, Los Alamos National Laboratory
Project started in: 2006
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 01/24/06
IRB approval number: LANL 06-0110
Explanation of IRB approval:
Study is closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 10
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
1. Brief description of the proposed research:
The first aim of this study is to obtain Raman spectra of biopsy samples of cervical tissue and to determine whether relative amounts of ribonucleic acid (RNA), deoxyribonucleic acid (DNA), glycogen, protein, and lipid in the cervical tissue can be determined. The second aim is to determine if this information can be used for diagnosis of cancers and pre-cancers.
A new Raman spectroscopy device will be tested on tissue specimens from subjects who are undergoing the loop electrosurgical excision procedure (LEEP). Participants will have agreed to have their tissue specimens measured with the Raman device just prior to placing the specimen in a container of formalin. There will be no Raman measurements on human subjects, only on removed tissue.
Success of the first goal, determining whether Raman spectroscopy can be used to determine the gross biochemical composition of the tissue, will be determined by answering the following questions: Are the residuals of the fits of the spectral data to biochemical components similar (e.g., within a factor of two) to the residuals that were obtained in recent published work on cells? Are the results that are obtained for biochemical composition similar to values published in the literature? Success of the second goal (determining whether Raman spectroscopy is useful for diagnostics) will be evaluated by determining if there is a correlation between changes in the Raman spectra and biochemical changes determined by Raman spectroscopy and changes in pathology.
2. Collaborating institution:
All clinical work is being performed with Dr. Harriet Smith (OB/Gyn) and Dr. Therese Bocklage (pathologist) at the University of New Mexico (UNM) Medical Center. This initial submission is for 20 patients.
3. Los Alamos National Laboratory (LANL) personnel:
The key personnel from LANL are Dr. Judith R. Mourant (Technical Services Manager) and Ms. Tamara Powers (senior technician).
4. Human subjects involvement and use of private information:
Patients who are regularly scheduled for a LEEP procedure will be contacted by UNM research personnel by phone and asked if they are interested in participating in the study. If they say yes, the consent form is read to them over the phone and they are asked if they have any questions. If the patient still wishes to participate, a hard copy of the consent form will be sent to them if there is time. Patients participating in the study are asked to show up early for their appointments so that a UNM researcher can go over the consent and Health Insurance Portability and Accountability Act (HIPAA) forms with them and get their signature.
The only potential risks to the patients are damage to the biopsy specimen by the Raman laser and the fact that there will be a class IIIb laser in the examination room. An assessment of the possibility of damage to the biopsy specimen is examined in depth in an attached document. The conclusion is that the laser will not damage the biopsy specimen. Engineering controls will be used to assure that the class IIIb laser is not an eye hazard to anyone.
In order to compare the Raman spectra to pathology results, the researchers at UNM must have access to identified medical records. A code will be used in all communications with LANL so that no PHI (public health information) will be sent to LANL. LANL personnel will be present at the medical examination/procedure (in order to run the Raman spectroscopy equipment) and therefore may have incidental access to PHI.
There is no compensation and there are no costs to the subjects.
5. A consent form is attached to this application.
6. The study will start as soon as we can schedule patients after IRB approval and will end when a sufficient number of biopsies have been measured on 8/1/2007.
7. The National Institutes of Health (NIH) is the sponsor for the project.
8. This is not an international collaboration nor is beryllium involved.
9. To the best of my knowledge, no key personnel have personal or financial interest in the study.
Study is closed.
LAUR-07-7356
"Center for HIV/AIDS Vaccine Immunology"
Principal Investigator: Ms. Bette Korber, Los Alamos National Laboratory
Project started in: 2006
This project ended in fiscal year 2007.
This is an international project.
Foreign Subjects No
Foreign Data Yes
Foreign Specimens No
Foreign Collaborators Yes
Foreign IRB Yes
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 02/14/06
IRB approval number: 06-02
Explanation of IRB approval:
Study was closed.
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: Duke University
Most recent approval: 07/21/06
IRB approval number: 8403-06-3R0BP
Explanation of additional approval:
Study was closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Abstract:
This is a study of human immunodeficiency virus (HIV) immune responses in populations with differences in host immune genes and differences in the infecting virus. The National Institutes of Health (NIH) funded this contract to explore the host immune response to HIV in populations that are likely vaccine sites. The baseline information will help both in the design of optimal vaccines for particular populations and in interpretation of vaccine trial immunogenicity results.
Whereas Europe and America have mainly HIV-1 subtype B, eastern Africa has predominantly subtypes A and D. Southern Africa on the other hand has mostly subtype C. Because of this viral variation and differences in highly variable immunologically important human genes in different regions of the world, a vaccine that is best for one location might not be optimal for another.
Publications that the Los Alamos National Laboratory (LANL) group has participated in to date:
1. Korber BT, Yusim K, Bhattacharya T, Goulder P, Leslie A, Kiepiela P, Mullins JI, Brander C, Walker B. Multiple factors impact negative associations between HIV sequence polymorphisms and HLA class I alleles. Submitted July 2005, LAUR#: 05-3897
2. Frahm N, Adams S, Kiepiela P, Linde CH, Hewitt HS, Lichterfeld M, Sango K, Brown NV, Pae E, Wurcel AG, Altfeld M, Feeney ME, Allen TM, Roach T, St John MA, Daar E, Rosenberg E, Korber B, Marincola F, Walker BD, Goulder PJR, Brander C. HLA-B63 (HLA-B*1516/B*1517) presents HLA-B57 and -B58 restricted CTL epitopes and is associated with low HIV viral load. J Virol. 2005 Aug; 79(16): 10218-25. PMID: 16051815
3. Leslie A, Kavanagh D, Honeyborne I, Pfafferott K, Edwards C, Pillay T, Hilton L, Thobakgale C, Ramduth D, Draenert R, Le Gall S, Luzzi G, Edwards A, Brander C, Sewell AK, Moore S, Mullins J, Moore C, Mallal S, Bhardwaj N, Yusim K, Phillips R, Klenerman P, Korber B, Kiepiela P, Walker B, Goulder P. Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA. J Exp Med. 2005 Mar 21; 201(6): 891-902. PMID: 15781581
4. Frahm N, Korber BT, Adams CM, Szinger JJ, Draenert R, Addo MM, Feeney ME, Yusim K, Sango K, Brown NV, SenGupta D, Piechocka-Trocha A, Simonis T, Marincola FM, Wurcel AG, Stone DR, Russell CJ, Adolf P, Cohen D, Roach T, StJohn A, Khatri A, Davis K, Mullins J, Goulder PJ, Walker BD, Brander C. Consistent CTL targeting of immunodominant regions in HIV across multiple ethnicities. J Virol. 2004 Mar; 78(5): 2187-2200. PMID: 14963115
5. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L, Zimbwa P, Moore S, Allen T, Brander C, Addo MM, Altfeld M, James I, Mallal S, Bunce M, Barber LD, Szinger J, Day C, Klenerman P, Mullins J, Korber B, Coovadia HM, Walker BD, Goulder PJ. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature. 2004 Dec 9; 432(7018): 769-75. PMID: 15592417
We have also developed the following public web sites and created the following web based analysis tools for the project:
1. http://www.hiv.lanl.gov/content/hiv-db/GENE_CUTTER/cutter.html
2. http://www.hiv.lanl.gov/content/immunology/hepitopes/index.html
3. http://www.hiv.lanl.gov/content/hiv-db/ELF/epitope_analyzer.html
4. http://www.hiv.lanl.gov/content/immunology/hlatem/index.html
We do not do any experimental work in the Theoretical division at Los Alamos. The National Institutes of Health (NIH) specified that the basic immunological information gained through this contract will be incorporated into the NIH-DOE sponsored database at Los Alamos, to facilitate HIV vaccine design in the developing world. So part of our task is to make the appropriate information concerning the immunologically reactive parts of the virus in Barbados, and in South Africa, available to HIV researchers through our LANL based HIV immunology database. Prior to public release of the data, we will work with our co-authors to assist them in analyzing the data and writing publications, then the published data will be made available to other researchers.
Blood is drawn from HIV positive patients attending participating clinical locations in the U.S., South Africa, and Barbados. Patients are asked if they would agree to have a blood sample be used for research purposes; this work may help to design an HIV vaccine and appropriate tests for vaccine trials in the region. Local IRB approved consent forms are used; copies of all of these and the initial IRB approval have been provided to the LANL/DOE IRB when the project was approved. There is no direct benefit to the patient, only possible benefit to their community and society. The patient is already attending the clinic and known to be HIV positive. Technology transfer is bringing immunology assays to South Africa and Barbados, and immunological testing is done on site. A small amount of the blood sample is shipped to Harvard and to the University of Washington. Host immune response genes are characterized, the viral sequence is obtained, the amount of virus in the sample measured, and the immune response determined. Viruses may be cultured or cells may be cultured for testing the immune response on site or at Harvard.
Minimal clinical records accompany the sample, essentially just the CD4 T-cell count, viral load, and treatment status, and the patient is given a coded ID for the purpose of the study and communication between investigators. Only the patient's physician has access to the code. The kind of data we are collecting is often found in scientific publications. The patient is being treated for being HIV positive, and this study does not compromise treatment or privacy. The primary risk involved is associated with the blood draw, and patients are fully informed concerning the research nature of the study. Their treatment is not influenced in any way by their choice to participate or not.
Study was closed.
LAUR-07-7356
"Retention of a Diverse Work Force at LANL"
Principal Investigator: Ms. Michelle B. Lee, Los Alamos National Laboratory
Project started in: 2006
This project ended in fiscal year 2007.
Status of the Research this Fiscal Year:
Current study is completed.
This project does not involve the use of multiple protocols/subprojects.
Institutional Review Board (IRB) Review:
Type of Review:
Expedited
Approving Institution: Los Alamos National Laboratory
Most recent approval: 03/29/06
Explanation of IRB approval:
Study is closed.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2007
Type(s) of Human Subjects Involvement:
Abstract:
[Human Subjects Research Review Board (HSRRB) Abstract]
General Information:
Principal Investigator: Michelle Blanchette Lee
Study Title: Retention of a Diverse Workforce at Los Alamos National Laboratory
Submission Date: March 20, 2006
1. A brief description of the proposed research:
a. Scientific Context: Background for Proposed Study:
Presently, many organizations are challenged with sustaining and managing a diverse workforce. Initially, organizations succeed in hiring women, racial minorities, and individuals with disabilities, but fail to retain this diverse talent. A report written by the Asian Pacific Islander (API) Career Enhancement Task Force (2000) recognized that a diverse management team and diverse workforce are vital for the future success of Los Alamos National Laboratory (LANL) as well as sustaining a world leadership position in science and technology. A diverse workforce maintains the competitiveness edge in the global economy and improves representation of the potential and current customers they serve; provide new insights into science, technology, and engineering; and enhance creativity and increase quality decisions.
Based on a LANL Total Minority Employment Fact Sheet generated June 2005, minorities comprise over one-third of the total regular laboratory population: Hispanic (~31 percent), Asian Pacific Islander (~3.9 percent), American Indian/Alaskan Native (~1.8 percent), and African American (AA) (~0.6 percent), and women comprise ~34 percent of the laboratory workforce. Recognizing the need to increase diversity in the workforce, LANL launched several programs and initiatives. For example, a goal was established to increase the number of African American employees to approximately one percent of the LANL workforce over five years (hire 75 AA employees). This goal was partially achieved. A report generated by the LANL Human Resources Workforce Data (December 15, 2004) showed that 80 AA employees (FY2000 to FY2004) were hired, but the AA population fluctuated between 0.5 percent and 0.7 percent, which is indicative of a retention problem. In addition, a report regarding African American Hires and Termination provided reasons for departing, which included the end of temporary assignments (Post Doc, GRA, Limited Term, etc.) and career advancement. Were employees, who departed because the