Hanford Radiological Protection Support Services Annual Report for 1999

During calendar year (CY) 1999, the Pacific Northwest National Laboratory (PNNL) performed its customary radiological protection support services in support of the U.S. Department of Energy (DOE) Richland Operations Office (RL) and the Hanford contractors. These services included: (1) external dosimetry, (2) internal dosimetry, (3) in vivo measurements, (4) radiological records, (5) instrument calibration and evaluation, and (6) calibration of radiation sources traceable to the National Institute of Standards and Technology (NIST). The services were provided under a number of programs as summarized here. Along with providing site-wide nuclear accident and environmental dosimetry capabilities, the Hanford External Dosimetry Program (HEDP) supports Hanford radiation protection programs by providing external radiation monitoring capabilities for all Hanford workers and visitors to help ensure their health and safety. Processing volumes decreased in CY 1999 relative to prior years for all types of dosimeters, with an overall decrease of 19%. During 1999, the HEDP passed the National Voluntary Laboratory Accreditation Program (NVLAP) performance testing criteria in 15 different categories. HEDP computers and processors were tested and upgraded to become Year 2000 (Y2K) compliant. Several changes and improvements were made to enhance the interpretation of dosimeter results. The Hanford Internal Dosimetry Program (HIDP) provides for the assessment and documentation of occupational dose from intakes of radionuclides at the Hanford Site. Performance problems carried over from CY 1998 continued to plague the in vitro bioassay contractor. A new contract was awarded for the in vitro bioassay program. A new computer system was put into routine operation by the in vivo bioassay program. Several changes to HIDP protocols were made that were related to bioassay grace periods, using field data to characterize the amount of alpha activity present and using a new default particle size. The number of incidents and high routine investigations that required follow-up were lower compared with 1998. Also, the number of excreta analyses performed decreased compared with CY 1998. The In Vivo Monitoring Program for Hanford (formerly the Hanford Whole Body Counting Project) provides the in vivo counting services for Hanford Site radiation workers. New computer hardware and software were put into routine operation to acquire, analyze, and store the measurement data. The technical procedures were revamped to reflect operational changes implemented with the new computer system. The U.S. Department of Energy Laboratory Accreditation Program (DOELAP) accreditation was extended to include two additional categories. New detectors were purchased for wound counting applications. The 8,085 in vivo measurements performed in 1999 represent a 2% decrease from 1998. Several high-purity germanium detectors were repaired at the In Vivo Radioassay and Research Facility, thereby saving out-of-service time and money compared with returning the detectors to the vendor. There were 11 phantom loans made through the DOE Phantom Library in 1999, including 2 international loans

HOX D13 expression across 79 tumor tissue types.

HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas-tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis

Neurologic complications of acute hepatitis E virus infection.

To assess the prevalence and clinical features of neurologic involvement in patients with acute hepatitis E virus (HEV) infection in Southern Switzerland. Among 1,940 consecutive patients investigated for acute hepatitis E, we identified 141 cases of acute of HEV infection (anti-HEV immunoglobulin M and immunoglobulin G both reactive and/or HEV RNA positive) between June 2014 and September 2017. Neurologic cases were followed up for 6 months. We compared patients with and without neurologic symptoms. Neurologic symptoms occurred in 43 acute HEV cases (30.4%) and consisted of neuralgic amyotrophy (NA, n = 15, 10.6%) and myalgia (n = 28, 19.8%). All NA cases were immunocompetent. Men had higher odds (OR = 5.2, CI 1.12-24.0, p = 0.03) of developing NA after infection with HEV, and in 3 couples simultaneously infected with HEV, only men developed NA. Bilateral involvement of NA was predominant (2:1) and occurred only in men. Seven NA cases were viremic (all genotype 3), but HEV was undetectable in their CSF. In the acute phase of NA, 9 patients were treated with intravenous immunoglobulin and 4 with prednisone, reporting no side effects and improvement in pain and strength. Myalgia occurred both without (n = 16) or with (n = 12) concomitant elevated serum creatinine kinase. Seven cases with myalgia in the shoulder girdle did not have muscle weakness ("forme fruste" of NA). Neurologic symptoms occurred in one-third of acute HEV infections and consisted of NA and myalgia. NA seems to occur more frequently in men infected by HEV and has a predominant (but not exclusive) bilateral involvement

Radiation and Health Technology Laboratory Capabilities

The Radiological Standards and Calibrations Laboratory, a part of Pacific Northwest National Laboratory (PNNL)(a) performs calibrations and upholds reference standards necessary to maintain traceability to national standards. The facility supports U.S. Department of Energy (DOE) programs at the Hanford Site, programs sponsored by DOE Headquarters and other federal agencies, radiological protection programs at other DOE and commercial nuclear sites and research and characterization programs sponsored through the commercial sector. The laboratory is located in the 318 Building of the Hanford Site's 300 Area. The facility contains five major exposure rooms and several laboratories used for exposure work preparation, low-activity instrument calibrations, instrument performance evaluations, instrument maintenance, instrument design and fabrication work, thermoluminescent and radiochromic Dosimetry, and calibration of measurement and test equipment (M&TE). The major exposure facilities are a low-scatter room used for neutron and photon exposures, a source well room used for high-volume instrument calibration work, an x-ray facility used for energy response studies, a high-exposure facility used for high-rate photon calibration work, a beta standards laboratory used for beta energy response studies and beta reference calibrations and M&TE laboratories. Calibrations are routinely performed for personnel dosimeters, health physics instrumentation, photon and neutron transfer standards alpha, beta, and gamma field sources used throughout the Hanford Site, and a wide variety of M&TE. This report describes the standards and calibrations laboratory

From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a “live” textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology

Randomized Controlled Trials of HIV/AIDS Prevention and Treatment in Africa: Results from the Cochrane HIV/AIDS Specialized Register

INTRODUCTION: To effectively address HIV/AIDS in Africa, evidence on preventing new infections and providing effective treatment is needed. Ideally, decisions on which interventions are effective should be based on evidence from randomized controlled trials (RCTs). Our previous research described African RCTs of HIV/AIDS reported between 1987 and 2003. This study updates that analysis with RCTs published between 2004 and 2008. OBJECTIVES: To describe RCTs of HIV/AIDS conducted in Africa and reported between 2004 and 2008. METHODS: We searched the Cochrane HIV/AIDS Specialized Register in September 2009. Two researchers independently evaluated studies for inclusion and extracted data using standardized forms. Details included location of trials, interventions, methodological quality, location of principal investigators and funders. RESULTS: Our search identified 834 RCTs, with 68 conducted in Africa. Forty-three assessed prevention-interventions and 25 treatment-interventions. Fifteen of the 43 prevention RCTs focused on preventing mother-to-child HIV transmission. Thirteen of the 25 treatment trials focused on opportunistic infections. Trials were conducted in 16 countries with most in South Africa (20), Zambia (12) and Zimbabwe (9). The median sample size was 628 (range 33-9645). Methods used for the generation of the allocation sequence and allocation concealment were adequate in 38 and 32 trials, respectively, and 58 reports included a CONSORT recommended flow diagram. Twenty-nine principal investigators resided in the United States of America (USA) and 18 were from African countries. Trials were co-funded by different agencies with most of the funding obtained from USA governmental and non-governmental agencies. Nineteen pharmaceutical companies provided partial funding to 15 RCTs and African agencies co-funded 17 RCTs. Ethical approval was reported in 65 trials and informed consent in 61 trials. CONCLUSION: Prevention trials dominate the trial landscape in Africa. Of note, few principal investigators and funders are from Africa. These findings mirror our previous work and continue to indicate a need for strengthening trial research capacity in Africa

Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis. METHODS: The expression of TLR-2, TLR-4 and CD14 in monocytes was analyzed by flow cytometry. To study the functional responses of these receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and the amounts of TNFα and IL-6 secreted were determined by ELISA. RESULTS: We found that the expression of TLR-2 was up-regulated in peripheral blood monocytes from COPD patients, either clinically stable or during AECOPD, as compared to never smokers or smokers with normal lung function. Upon stimulation with TLR-2 ligand monocytes from COPD patients secreted increased amounts of cytokines than similarly stimulated monocytes from never smokers and smokers. In contrast, the expressions of TLR-4 and CD14 were not significantly different between groups, and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not significantly different either. At discharge from hospital TLR-2 expression was down-regulated in peripheral blood monocytes from AECOPD patients. This could be due to the treatment with systemic steroids because, in vitro, steroids down-regulated TLR-2 expression in a dose-dependent manner. Finally, we demonstrated that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro TLR-2 expression in monocytes from never smokers. CONCLUSION: Our results reveal abnormalities in TLRs expression in COPD patients and highlight its potential relationship with systemic inflammation in these patients

Committing curriculum time to science literacy: The benefits from science based media resources

Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC-restricted manner. To investigate how AZT sensitizes PELs to immune control we first examined BJAB cells transduced with individual KSHV-latent genes for their ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL receptors. This showed that in addition to the previously described vFLIP protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli. Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited in the presence of AZT as was a second vIRF3 associated phenotype, the downregulation of surface MHC class II. Although both vFLIP and vIRF3 are expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be sufficient to restore T cell control of these tumor cells

Hepatitis B Virus Infection Is Associated With Impaired Immunological Recovery During Antiretroviral Therapy in the Swiss HIV Cohort Study

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients worldwide. It is unclear whether HIV-related outcomes are affected by HBV coinfection. We compared virological suppression and immunological recovery during antiretroviral therapy (ART) of patients of different HBV serological status in the Swiss HIV Cohort Study. CD4 cell recovery during ART was significantly impaired in hepatitis B surface antigen-positive patients and in those with anti-hepatitis B core antigen alone compared with HBV-uninfected patients, despite similar virological efficacy of ART. CD4 increase in patients with resolved HBV infection was similar to that in HBV-uninfected individual