Ms. Kathy
L.
Delucas
Los Alamos National Laboratory
Public Affairs Office, CER-20
P. O. Box 1663, MS A104
Los Alamos, NM 87545
Phone: 505-667-5225
Fax: 505-665-3910
E-mail: duke@lanl.gov
Number of Human Subjects projects reported: 23
| 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 (00-07) | "Polarized Elastic Scattering Spectroscopy System" |
| LANL-01-12 (01-06) | "Early Detection and Genotyping of Influenza Strains (Formerly Titled: Early Detection of Influenza Strains)" |
| LANL-01-15 (01-09) | "Optical Biosensor for the Early Detection of Breast Cancer" |
| LANL-01-16 (01-11) | "Joint Protective Air Crew Ensemble, JPACE. Formerly known as Air Warrior Dirty Doffing Test" |
| LANL-01-17 (01-12) | "Transmission and Viral Dynamics of Drug Resistant HIV-1" |
| 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-03-03 | "Bio-Surveillance Analysis Feedback Evaluation and Response (B-SAFER)" |
| 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-04-04 | "Improved Dosimetry and Risk Assessment for Plutonium-Induced Lung Disease: Phase III" |
| 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-04-09 | "Integrated Analysis of Multi-Modality Functional Imaging Data" |
| LANL-04-10 | "HLA Typing and Epitope Mapping Realtive to HIV Vaccine Design-Contract #2" |
| LANL-05-01 | "Ultra Low Field Magnetic Resonance Imaging" |
| LANL-05-02 | "Evaluation of the Unreviewed Safety Question Training Process at the Los Alamos National Laboratory Nuclear Facilities" |
| LANL-05-03 | "Nanocrystal Quantum Dots" |
| LANL-05-04 | "Raman Spectroscopy for the Diagnosis of Cancer in the GI Tract" |
Other projects of interest associated with this site:
| JHUSHP-97-DE-FC03-98SF21541 | "Medical Surveillance for Former Department of Energy Workers" |
| 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
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: 02/11/05
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 2005
Type(s) of Human Subjects Involvement:
Study Title: Manhattan Project Plutonium Workers 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 WWII. 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. In the most recent contact with these workers, the workers provided updated medical records and histories.
This updated information on the medical condition of the surviving cohort members will be analyzed and used for an updated publication. The individuals will not be identified in this 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.
Internal comparisons of mortality among the study cohort with mortality among an internal comparison cohort, which was selected based on similar work history and age, may be conducted. Mortality follow-up for the comparison cohort will be updated through an agreement with the National Death Index. Comparing mortality among the study group with mortality among the internal comparison group should reduce the impact of the healthy worker effect or other types of selection bias. This mortality follow-up of the comparison population has been conducted in previous updates of this study and has been reported in previous papers.
Urine bioassay samples have historically been collected from the subjects in the Manhattan District workers cohort at LANL during the entire period that the study has been ongoing. The latest samples were collected from surviving subjects in autumn 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. Since previous samples were collected about every six years, more frequent sampling is desirable, but not more than once yearly. An important scientific question that can be addressed with additional samples is whether age-related osteoporosis results in an increase in the rate of Pu urinary excretion. Because current biokinetic models do not take this possibility into account, it is important to document whether the phenomenon occurs. It is anticipated that at least two reports will be prepared as a result of these efforts. One report will deal with the results of the review of medical conditions and mortality analyses, and the other will deal with the improved, updated dose assessments.
LA-UR-06-1175
"Neuromagnetic Mapping of Functional Centers in the Human Brain"
Principal Investigator: Dr. Robert H. Kraus, Jr., Los Alamos National Laboratory
Project started in: 1998
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: 02/11/05
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 2005
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 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 principals 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 LANL superconducting imaging surface (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 FY2004 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 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 FY2004 focused on signal quality improvement by noise rejection methods, comparing features of signal-to-noise and temporal details of the signal, localization reliability and accuracy by combining MEG and EEG. The evoked response 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-06-1175
"Polarized Elastic Scattering Spectroscopy System"
Principal Investigator: Dr. Judith R. Mourant, Los Alamos National Laboratory
Project started in: 2001
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: 11/30/04
IRB approval number: LANL 00-07
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 03/08/05
IRB approval number: 00-282
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 2005
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 criteria 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-06-1175
"Early Detection and Genotyping of Influenza Strains (Formerly Titled: Early Detection of Influenza Strains)"
Principal Investigator: Dr. P. Scott White, Los Alamos National Laboratory
Project started in: 2001
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: 02/11/05
IRB approval number: LANL 01-06
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: University of New Mexico
Most recent approval: 03/21/01
IRB approval number: HRRC: 01-078
Explanation of additional approval:
Exempt approval by the University of New Mexico
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 40
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
Study Title: Early Detection and Genotyping of Influenza Strains (Formerly Titled: Early Detection of Influenza Strains)
Influenza, caused by influenza viruses, is a highly contagious acute respiratory disease. Rapid and accurate detection and differentiation of influenza virus types (A versus B), subtypes, and optimally strains are essential for influenza surveillance, vaccine development, therapeutic treatment, and infection control. In this project, we will use both the genetic and antigenic approaches developed at LANL to characterize influenza virus isolates for improved influenza surveillance and diagnostics. Clinical specimens (throat, nasal or nasopharyngeal swabs, nasopharyngeal aspirates, or broncho-alveolar lavages from patients with febrile respiratory illness) will be collected and forwarded to LANL by our collaborator, a non-profit organization that provides analytical data for clinical samples. The laboratory propagates putative influenza samples in mammalian tissue cultures and routinely isolates ribonucleic acid (RNA) from these samples using commercial RNA isolation kits (guanadinium lysis and spin columns; Qiagen, Inc.). This process results in the isolation and purification of the negative RNA strand that is not infectious. We will use this RNA extracted by our collaborators to sequence the whole influenza genome (~15 kb). Meanwhile, part of the properly stored specimen will be analyzed by our immunoassay for viral protein (antigenicity) characterization.
At LANL our basic genetic protocol will be the reverse transcription of the RNA samples and subsequent polymerase chain reaction (PCR) amplification of the eight segments of the influenza genome. These amplified products will then be sequenced using standard protocols within the Production Sequencing Facility or other smaller sequencing units within LANL. The RNA sequence will be analyzed to identify distinguishing characters that define evolutionary relationships among strains. A microsphere-based genotyping assay will be developed to detect these identifying characters to enable rapid, nucleic acid-based influenza surveillance. On the other hand, the antigenic protocol will be used to test the specimen directly on our unique immunoassay using viral proteins. Currently at LANL, we are developing a rapid and sensitive microsphere-based immunoassay for influenza virus typing and subtyping by flow cytometry. The conceptual assay design can be described as follows: micron-sized polymer particles (microspheres) covalently coupled with type- and subtype-specific monoclonal antibodies are used to capture the influenza virus in the sample. This complex is then incubated with fluorophore-conjugated reporter polyclonal antibody (against influenza) and analyzed on a multiparameter flow cytometer. Inactivated influenza viruses are being used for the assay development at the present stage. However, further assessment of assay performance cannot be completed without testing live viruses in tissue culture or clinical specimens. The clinical specimens will come from the same collaborator and will be de-identified. The success of this project will have significant impact on the influenza diagnostics and surveillance, and also aid in the vaccine development.
The total number of samples to be collected will be in the range of 20 to 50 samples per year, depending on availability. Samples will be coded to indicate the date and location of collection and will not be associated with identifying information. Samples obtained from our collaborators are collected through the New Mexico Department of Health influenza surveillance activities, and as such, have no consent form associated with them. These activities were reviewed by the University of New Mexico IRB and are approved as Exempt (but as Expedited by the LANL IRB).
LA-UR-06-1175
"Optical Biosensor for the Early Detection of Breast Cancer"
Principal Investigator: Dr. Basil I. Swanson, Los Alamos National Laboratory
Project started in: 2001
This project ended in fiscal year 2005.
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: 07/27/04
IRB approval number: LANL 01-09
Explanation of IRB approval:
Study not submitted for renewal.
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: City of Hope National Medical Center
Most recent approval: 04/13/04
IRB approval number: 00080
Explanation of additional approval:
Last approval date reveived from PI and City of Hope National Medical Center
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 2005
Type(s) of Human Subjects Involvement:
Abstract:
Study Title: Optical Bio-Sensor for the Early Detection of Bresat Cancer
Abstract: The overarching objective is to develop a sensor system that could be used for the early detection of antigenic markers for breast cancer to aid in the diagnosis and monitoring of cancer. Currently, the diagnosis of breast cancer is limited to self-exam, clinical exam, and mammography. Mammography is the best of these diagnostic tools and yet it is quite expensive and has significant problems with both false positives and false negatives. The development of a quick, simple diagnostic tool based on the detection of a panel of tumor markers would greatly improve the management of this disease. The biosensor platform and assays are being developed at Los Alamos and the clinical study is being performed at the City of Hope. The human patient studies are being conducted under the auspices of the City of Hope IRB (protocol # 00080) as well as the Los Alamos National Laboratory Human Subject Protocol 01-09.
In the R21 phase we have demonstrated the optical biosensor for the detection of carcinoembrionic antigen (CEA) and in the R33 phase we will fully develop assays for three additional tumor markers including prostaglandin cell derived growth factor (PCDGF), Her2/neu and CA15.3 (MUC-1). We have established a detection limit for CEA using this approach and have demonstrated a dynamic range for quantitation that will cover the observed clinical levels of CEA. We have demonstrated a detection limit that is better than current laboratory-based assays and have shown that the assay can be completed in less than 10 minutes. All patients that were enrolled for the R21 study were referred to the City of Hope clinic as a result of an abnormal mammogram on one breast. The original hypothesis was that the contralateral breast (the breast NOT showing an abnormal mammogram) would provide a control. During the course of the R21 study we found no significant difference in CEA levels between the breast with the lesion and the contralateral breast. We did, however, find a significant decrease in the level of CEA for those patients with invasive ductal carcinoma relative to the pool that had non-invasive ductal carcinoma (DCIS).
We were unable to enroll normal controls in the R21 study owing to the limited access to patients. In the R33 phase we will be able to enroll both normal controls and patients with breast cancer. Nipple aspirate fluids will be collected from both breasts using a nipple aspirate fluid (NAF) breast pump procedure developed by Susan Love. The intra-patient variability in CEA levels detected in NAF will be determined by collecting replicate samples from the same patient as described in the City of Hope protocol. Sample collection will not interfere with the patients' treatment schedule. When allowed for by the treatment schedule, replicate samples will be collected with at least a two-day interval prior to the patient's treatment (surgery/biopsy). In addition, NAF will be collected from patients' 30-day post-treatment at the regular follow-up examination. When possible a duplicate post-treatment NAF will be collected with a two-day interval. Data from these replicate samples were examined statistically as described in Section VIII.B of the City of Hope protocol. Specifically reproducibility of the NAF CEA assay will be assessed using data from replicate samples within each group (cancerous breast, benign diseased breast, and bilateral healthy breast) by the intra-class correlation coefficient (ICC).
Blood samples (10 mililiters) will be drawn from each patient and tumor marker levels will be determined by Elisa immunoassay (EIA) and by the biosensor analysis. NAF will be obtained from each breast on each patient. All of the data will be coded and used for this study only. The risks to the patient are minimal. Routine blood draws carry a small risk of a transient hematoma. We know of and anticipate no risk associated with obtaining the NAF. If a rash or other problem develops, we will treat the patient with an appropriate ointment. The patients' names and study results will be coded and kept confidential. The data will be retained by the Principal Investigator in a locked file draw in his office.
The levels of CEA, PCDGF, Her2/neu and CA15.3 will be measured using the waveguide-based biosensor for both serum and NAF samples as described above. Human serum albumin will also be measured as a reference. We expect to make these measurements in the third year of the R33 phase after having optimized the assay for all four markers and the human serum albumin (HAS) reference in the first two years.
LA-UR-06-1175
"Joint Protective Air Crew Ensemble, JPACE. Formerly known as Air Warrior Dirty Doffing Test"
Principal Investigator: Mr. Fredric N. Bolton, Los Alamos National Laboratory
Project started in: 2001
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: 10/26/04
IRB approval number: LANL 01-11
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 2005
Type(s) of Human Subjects Involvement:
Study Title: Joint Protective Air Crew Ensemble (JPACE)
(Formerly: "Air Warrior Dirty Doffing Test")
Scientific Context and Objectives:
This study is a continuation of work performed for JPACE Testing during FY2002. One of the JPACE objectives is that the selected garment be capable of providing protection to both the wearer and assistants during the doffing process following completion of a military mission. The objective of this phase of the study is to determine how the effectiveness of the protective garments may be improved during post-mission doffing and decontamination.
Hypothesis:
The hypothesis to be tested is that the protection afforded to the wearer and assistants can be greatly improved through a combination of decontamination methods and doffing technique.
Experimental Design:
This phase of the study involves similar combinations of protective garments and equipment, and test subjects previously identified for JPACE work will be asked to participate. A variety of methods of decontamination (dry removal, wetting garment surfaces, etc.) will be employed to determine which combinations of decontamination method and doffing technique appear to provide better overall protection from contamination transfer to bare skin.
Privacy and Confidentiality:
Approved advertisements are used to recruit subjects. Personal identifiers will not be disclosed without written permission of the test subjects, except if necessary to protect subjects' rights and/or welfare or if required by law. The study material and identifying information will be kept locked in filing cabinets.
Procedures Involving Human Subjects:
As with previous JPACE work, human subjects will be dressed in the appropriate combination of protective garment and equipment. Once dressed in the military garb, the subjects will be exposed to a tracer (e.g., fingerprint powder), which will be used to visually track the transfer of contamination to the wearer's skin during the doffing process.
The known risks to human subjects include:
· Brief inhalation exposure to airborne tracer materials (e.g., fingerprint powder) while fully garbed in military protective gear (including respiratory protection).
· Potential contact between the tracer material and unprotected skin (e.g., neck, wrists, and ankles).
· Slightly elevated risk of heat stress (a combination of the protective clothing and respirator).
· Slightly elevated risk of cold stress arising from the use of wet decontamination methods.
· Potential for brief exposure to ultraviolet light during test evaluation (post-doffing) and digital imaging.
The main record of interest for this phase of JPACE continues to be the digital images collected after the military garb has been doffed. Key to success of the work is the ability to qualitatively discern the differences in performance between different combinations of decontamination method and doffing technique. The study is expected to result in information that will be useful to military planners in establishing appropriate decontamination and doffing procedures for potentially contaminated air crew members and assistants. The study will be terminated when the final JPACE garment design has been accepted by the DoD.
LA-UR-06-1175
"Transmission and Viral Dynamics of Drug Resistant HIV-1"
Principal Investigator: Dr. Alan S. Perelson, Los Alamos National Laboratory
Project started in: 2001
This project ended in fiscal year 2005.
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: 09/10/04
IRB approval number: LANL 01-12
Explanation of IRB approval:
Study not submitted for renewal.
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: The Rockefeller University
Most recent approval: 06/03/04
IRB approval number: MMA-0340-0604
Explanation of additional approval:
Approval dates: 7/3/2004 through 7/2/2005
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
Study Title: Transmission and Viral Dynamics of Drug Resistant HIV-1
Objectives: This is an National Institutes of Health (NIH)-funded project aimed at understanding the virological determinants that govern the transmission, fitness, and in vivo replication dynamics of multi-drug resistant human immunodeficiency virus-type 1 (HIV-1).
The project has three specific aims:
1. Use genotypic and phenotypic methods to determine whether drug resistant HIV-1 variants are being transmitted with increasing prevalence.
2. Determine how the replicative characteristics and relative fitness of drug resistant viruses may affect the transmission of HIV-1 infection.
3. Use intervention-based clinical studies to define the replication dynamics of drug resistant variants of HIV-1 in vivo.
Methodology: To accomplish Aim 1, blood will be drawn and HIV isolated, and tested for resistance to antiretroviral drugs.
To accomplish Aim 2, wild-type and drug resistant virus will be grown in cell culture. By measuring the fraction of viruses in culture that are drug-resistant at different times, one can compute the fitness of the drug-resistant virus relative to the wild-type.
In Aim 3, the concentration of HIV-1 in plasma will be measured as a function of time patients have been on antiretroviral drug therapy. Mathematical models of HIV-1 replication in individuals undergoing drug therapy will be used to analyze the data obtained from the study subjects. From such an analysis one can deduce how fast subjects are clearing HIV from their blood stream and how rapidly the virus is killing infected cells. We are interested in learning how these rates change in patients infected with drug-resistant virus versus wild-type virus.
Ionizing Radiation, Radioactive Substances, or Chemical Substances: None.
Involvement of Human Subjects: Work at LANL will only involve statistical analysis and mathematical modeling of data obtained elsewhere. The data will be sent to LANL with patients identified in coded form. The data will include patient coded identification numbers, time since start of therapy, HIV RNA/ml CD4 count, and the fraction of the HIV RNA that is wild-type or drug resistant. No personal information about the patients will be obtained.
LA-UR-06-1175
"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 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: 12/20/04
IRB approval number: LANL 02-02
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 2005
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 project aims to improve the timeliness of incident-related dose assessments by providing radiometric measurements of actinides in fecal samples within 24 to 48 hours after worker inhalation exposure, which is up to two weeks sooner than is currently possible using existing radiochemical methods for analyzing urine bioassay samples. The methods to be developed involve using a specialized photon detector that can measure small amounts of Pu, Am, Cm in minimally processed fecal samples. To do this study, human fecal samples obtained from unexposed volunteers are needed. To date, such samples have been obtained from five volunteers. The samples were obtained without any labeling or personal identifiers, and are maintained frozen as anonymous samples in a locked freezer until needed for the study. No progress was made during FY2005 because of other commitments of the investigators. To date, a method for reducing the volume of fecal samples by 75 percent has been identified. This is adequate to allow the entire sample to be counted within the active volume of the photon counter. As before, there is no risk to the volunteers who contribute fecal samples.
LA-UR-06-1175
"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
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: 09/29/05
IRB approval number: LANL 02-10
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston, Mass.
Most recent approval: 09/29/05
IRB approval number: MGH: 2001-P-001941
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston Mass.
Most recent approval: 10/06/05
IRB approval number: 2001-P-000012
Explanation of additional approval:
Most current approval date for continuation
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston Mass.
Most recent approval: 10/15/04
IRB approval number: 2002-P-000063
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital, Boston Mass.
Most recent approval: 09/19/05
IRB approval number: 2002-P-000132
Type of Review:
Full Board
Approving Institution: Massachusetts General Hospital, Boston, Mass.
Most recent approval: 07/14/05
IRB approval number: MGH: 2004-P-001730
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 2005
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 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 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 can break 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-06-1175
"Bio-Surveillance Analysis Feedback Evaluation and Response (B-SAFER)"
Principal Investigator: Dr. Edward L. Joyce, Los Alamos National Laboratory
Project started in: 2003
This project ended in fiscal year 2005.
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: 08/11/04
IRB approval number: LANL 03-03
Explanation of IRB approval:
Study closed 7/19/2005.
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 2005
Type(s) of Human Subjects Involvement:
Abstract:
Study Title: Bio-Surveillance Analysis Feedback Evaluation and Response (B-SAFER)
Concern about natural and man-made threats to public health has resulted in the adoption of syndromic surveillance to extend the capabilities of the public health department in early detection of a disease outbreak. The efficacy of syndromic surveillance is still being evaluated, but it is being widely adopted as an important strategy for identifying bioterrorism events. Surveillance needs to be able to quickly detect the nature and scale of an event to assist both local public health and healthcare organizations and nationwide and even worldwide health authorities (in the case of Severe Acute Respiratory Syndrome (SARS), for example). This need for simultaneous information at multiple levels requires both data standards and component functional standards so that systems can work individually and together in a transparent manner. We briefly describe a pilot demonstration of such system architecture as well as a mechanism for making such a system widely available for rapid deployment. Finally, we describe techniques for increasing the sensitivity and specificity of syndromic surveillance to possibly detect an outbreak before an individual physician identifies it.
IEEE Journal Engineering in Biology and Medicine, January 2004
LA-UR-06-1175
"HIV Compartmentalization in Women: Virus and CTL Response"
Principal Investigator: Dr. Carla L. Kuiken, Los Alamos National Laboratory
Project started in: 2003
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: 02/13/05
IRB approval number: LANL 03-04
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: State of New York Department of Health
Most recent approval: 06/22/05
IRB approval number: 00-312
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 approval notification received dated 1/13/2006 with an expiration date of 1/25/2007.
Type of Review:
Expedited
Approving Institution: SUNNY Downstate Medical Center, Brooklyn NY
Most recent approval: 02/24/05
IRB approval number: 90-129
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 2005
Type(s) of Human Subjects Involvement:
Study Title: HIV Compartmentalization in Women: Virus and CTL Response
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.
LA-UR-06-1175
"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
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: 05/01/05
IRB approval number: LANL 03-07
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 2005
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.
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.
LA-UR-06-1175
"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
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: 10/28/04
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 2005
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.
LA-UR-06-1175
"Improved Dosimetry and Risk Assessment for Plutonium-Induced Lung Disease: Phase III"
Principal Investigator: Dr. Raymond A. Guilmette, Los Alamos National Laboratory
Project started in: 2004
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: 01/08/05
IRB approval number: LANL 04-04
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: Southern Urals Biophysics Institute, Russia
Most recent approval: 10/17/05
Explanation of additional approval:
International study review schedule
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 2005
Type(s) of Human Subjects Involvement:
Study Title: Improved dosimetry and risk assessment for plutonium-induced disease: Phase III
This study is a continuation of previous work conducted at Lovelace Respiratory Research Institute (LRRI), IRB protocol 98-036, and funded under a grant awarded by the Office of International Health Programs, DOE/EH-51, as part of the research program of the Joint Coordinating Committee for Radiation Effects Research (JCCRER). The original project grant focused on measuring the distribution of plutonium (Pu) particles in fixed lung tissue from deceased workers from the Mayak Plutonium Production Association (MPA) using a combination of stereological sampling and quantitative autoradiography. This experimental work was done at both LRRI and SUBI (Southern Urals Biophysics Institute, Ozyorsk, Russia). This continuation project changes the emphasis of the work. The new hypotheses are: 1) The current human respiratory tract and systemic biokinetic models do not adequately describe the Pu distribution data from the MPA Pu workers; and 2) theoretically derived dose and dose rate patterns from Pu retained in the lung can be used to specify dose uniformity factors for radiation protection and epidemiology. The first hypothesis will be addressed using the data available from Pu radiochemical analysis of soft tissues and bone of about 600 deceased Mayak workers. This data set is part of the SUBI tissue archive, and is supplemented by varying amounts of urine and fecal bioassay data for these same individuals. All the work associated with these sanitized data will involve testing the structures and parameter values for the most contemporary Pu dosimetry models. The study will also use the richness of these data to characterize the magnitude of uncertainty inherent in these models and develop methods (likely involving Bayesian statistical inference) for applying these uncertainties to improve dose estimates for individuals in the Mayak worker population. This latter work will impact directly on the quality of dosimetry data available for retrospective epidemiological investigations of lung, liver, and bone cancer risk from internalized Pu.
The studies associated with the second hypothesis will involve experimental work done solely at SUBI. One or more fixed whole lung specimens from deceased subjects will be acquired according to the rules and regulations of the SUBI IRB (their IRB policies and consent forms have received the concurrence of the U.S. DOE). Briefly, the lung specimens will be fixed at simulated atmospheric pressure so that proper lung inflation is achieved and sampled using stereological techniques. Histological sections will be prepared and the target anatomic structures digitized to provide maps of the microscopic anatomy of normal human lung. Pu particles will be theoretically placed in areas of the lung shown to contain such particles. This placement will be guided by the results obtained in the Phase I and II parts of this project. Then Monte Carlo methods will be used to simulate the local dose-rate patterns in different cell populations of the lung arising from the alpha particles emitted from the theoretical Pu particles. These results will provide a technical basis for developing a scheme for quantifying the degree of non-uniformity of irradiation of the various lung tissue types.
As has always been the case in this study, no personal information will be available to LANL researchers; subjects are identified solely by case numbers, and the key to the identification of each subject lies solely in the control of the SUBI scientists.
LA-UR-06-1175
"HIV-1 Diversity in Optimized Vaccine Selection"
Principal Investigator: Dr. Karina Yusim, Los Alamos National Laboratory
Project started in: 2004
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: 01/23/05
IRB approval number: LANL 04-05
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital
Most recent approval: 09/30/05
IRB approval number: 2001-P-001941/9
Type of Review:
Expedited
Approving Institution: Mass. Dept. of Public Health, Lemuel Shattuck Hospital
Most recent approval: 09/16/05
IRB approval number: 05-PARC011
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 2005
Type(s) of Human Subjects Involvement:
Study Title: HIV-1 Diversity I Optimized Vaccine Selection
The extraordinary scale of HIV variation poses a major obstacle for AIDS vaccine development. The HIV Database in 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.
LA-UR-06-1175
"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
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: 05/20/05
IRB approval number: LANL 04-06
Additional IRB approvals from other institutions:
Type of Review:
Full Board
Approving Institution: Central Beryllium IRB
Most recent approval: 05/19/05
IRB approval number: CBeIRB(04)-19
Type of Review:
Expedited
Approving Institution: University of Pennsylvania
Most recent approval: 01/07/05
IRB approval number: 800836
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 2005
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 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 numer, address, telephone number, or any other direct personal identifier) is given to LANL.
LA-UR-06-1175
"Spatiotemporal Imaging of Human Visual System Processing"
Principal Investigator: Dr. John S. George, Los Alamos National Laboratory
Project started in: 2004
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: 05/20/05
IRB approval number: LANL 04-07
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital, Boston, Mass.
Most recent approval: 10/24/04
IRB approval number: 1999-P-010946/27
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 2005
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 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 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.
LA-UR-06-1175
"Integrated Analysis of Multi-Modality Functional Imaging Data"
Principal Investigator: Dr. David M. Schmidt, Los Alamos National Laboratory
Project started in: 2004
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: 08/31/05
IRB approval number: LANL 04-09
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 3
Reporting period for number of human subjects:
Fiscal Year 2005
Type(s) of Human Subjects Involvement:
Title of Research: Integrated Analysis of Multi-Modality Functional Imaging Data
ABSTRACT:
As part of a National Institutes of Health (NIH)/National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant, we are developing and testing methods to analyze MEG/EEG human brain mapping data using the probabilistic technique of Bayesian inference. Unlike other approaches, our approaches do not result in a single best solution to the problem, rather, they yield a probability distribution of solutions upon which all subsequent inferences are based. This is significant because there are many different solutions that could give rise to the same data. While much of our work involves simulated data, we also need to use empirical data to test and demonstrate our analysis methods. We use retrospective data that were obtained at another institution under their approved IRB rules and have been de-identified. This data consists of MEG, functional MRI, and anatomical MRI data from one normal subject that were taken using electrical median nerve stimulation at the Veterans Administration (VA) Medical Center in Albuquerque.
The approved University of New Mexico (UNM)/VA project title is "Pharmacologic functional brain imaging using amphetamine and acetazolamide" (UNM/VA Human Research Review Committee (HRRC) # 00-342), which is in part a study of pharmacological agents but includes a methods development component involving no pharmacological agents. It includes data gathered in this latter component that we are using for this study.
The data were acquired in March of 2002, so that Health Insurance Portability and Accountability Act (HIPAA) does not apply. Data are sent to us with identifying features, and we de-identify the data and delete the original data files. We use three types of data: MEG, functional MRI (fMRI) and anatomical MRI. All three types contain identifying information in the header fields of their files. We apply programs that strip the identifying features from these header fields. This process does not reveal the subject's identifying information. In addition, the anatomical MRI data itself can be used to form an image of the subject's face using 3-dimensional reconstruction algorithms. To de-identify this aspect of the data, we use another program to apply a mask over the facial features and then to blur the facial features with the mask so that the facial features cannot be reconstructed. This process also does not reveal identifiable features because the task of applying a mask is done using 2-dimensional views of the data.
Glossary of Terms:
MEG - Magnetoencephalography
EEG - Electroencephalograpy
MRI - Magnetic Resonance Imaging
LA-UR-06-1175
"HLA Typing and Epitope Mapping Realtive to HIV Vaccine Design-Contract #2"
Principal Investigator: Dr. Thomas K. Leitner, Los Alamos National Laboratory
Project started in: 2004
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: 09/21/05
IRB approval number: LANL 04-10
Additional IRB approvals from other institutions:
Type of Review:
Expedited
Approving Institution: Massachusetts General Hospital
Most recent approval: 09/29/05
IRB approval number: 2003-P-001990/1
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 2005
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 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 - 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
LA-UR-06-1175
"Ultra Low Field Magnetic Resonance Imaging"
Principal Investigator: Dr. Robert H. Kraus, Jr., Los Alamos National Laboratory
Project started in: 2005
Funding for Human Subjects Research:
This project does not involve the use of multiple