Independent Orbiter Assessment (IOA): Assessment of the landing/deceleration (LDG/DEC) subsystem FMEA/CIL

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA effort first completed an analysis of the Landing/Deceleration (LDG/DEC) hardware, generating draft failure modes and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The IOA contained within the NASA FMEA/CIL documentation. The IOA results were then compared to the NASA FMEA/CIL baseline with proposed Post 51-L updates included. A resolution of each discrepancy from the comparison is provided through additional analysis as required. This report documents the results of that comparison for the Orbiter LDG/DEC hardware. The IOA product for the LDG/DEC analysis consisted of 259 failure mode worksheets that resulted in 124 potential critical items being identified. Comparison was made to the NASA baseline which consisted of 267 FMEA's and 120 CIL items. This comparison produced agreement on all but 75 FMEA's which caused differences in 51 CIL items

Motion sickness susceptibility under weightless and hypergravity conditions generated by parabolic flight

Motion sickness susceptibility under weightless and hypergravity conditions generated by parabolic fligh

Independent Orbiter Assessment (IOA): Analysis of the guidance, navigation, and control subsystem

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) is presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. The independent analysis results corresponding to the Orbiter Guidance, Navigation, and Control (GNC) Subsystem hardware are documented. The function of the GNC hardware is to respond to guidance, navigation, and control software commands to effect vehicle control and to provide sensor and controller data to GNC software. Some of the GNC hardware for which failure modes analysis was performed includes: hand controllers; Rudder Pedal Transducer Assembly (RPTA); Speed Brake Thrust Controller (SBTC); Inertial Measurement Unit (IMU); Star Tracker (ST); Crew Optical Alignment Site (COAS); Air Data Transducer Assembly (ADTA); Rate Gyro Assemblies; Accelerometer Assembly (AA); Aerosurface Servo Amplifier (ASA); and Ascent Thrust Vector Control (ATVC). The IOA analysis process utilized available GNC hardware drawings, workbooks, specifications, schematics, and systems briefs for defining hardware assemblies, components, and circuits. Each hardware item was evaluated and analyzed for possible failure modes and effects. Criticality was assigned based upon the severity of the effect for each failure mode

Independent Orbiter Assessment (IOA): Analysis of the reaction control system, volume 3

The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results for the Reaction Control System (RCS). The RCS is situated in three independent modules, one forward in the orbiter nose and one in each OMS/RCS pod. Each RCS module consists of the following subsystems: Helium Pressurization Subsystem; Propellant Storage and Distribution Subsystem; Thruster Subsystem; and Electrical Power Distribution and Control Subsystem. Volume 3 continues the presentation of IOA analysis worksheets and the potential critical items list

Stressful and traumatic life events as disruptors to antiretroviral therapy adherence

Stressful and traumatic life events (STLEs) are common among HIV-infected individuals and may affect health behaviors such as adherence to antiretroviral (ARV) therapy, with important implications for treatment outcomes. We examined the association between STLEs and ARV adherence among 289 US-based participants enrolled between 7/1/2010 and 9/1/2013 in a study of depression treatment for HIV-infected patients. Participants received monthly telephone calls to assess STLEs and pill count-based ARV adherence. Inverse probability of observation weighting was combined with multiple imputation to address missing data. Participants were mostly male (71%) and black (63%), with a median age of 45 years. Median monthly adherence was 96% (interquartile range (IQR): 85–100%). Participants experienced a mean of 2.48 STLEs (range: 0–14) in the previous month. The presence of ≥2 STLEs was associated with a mean change in adherence of −3.67% (95% confidence interval (CI): −7.12%, −0.21%) and decreased likelihood of achieving ≥95% adherence (risk ratio (95% CI) = 0.82 (0.71, 0.95)). For each additional STLE, the mean adherence change was −0.90% (95% CI: −1.79%, 0.00%). STLEs were associated with poorer ARV adherence, including decreased likelihood of adhering to ≥95% of ARV doses. This level of adherence has a critical role in regimen effectiveness and prevention of resistance

White paper: CeLAND - Investigation of the reactor antineutrino anomaly with an intense 144Ce-144Pr antineutrino source in KamLAND

We propose to test for short baseline neutrino oscillations, implied by the recent reevaluation of the reactor antineutrino flux and by anomalous results from the gallium solar neutrino detectors. The test will consist of producing a 75 kCi 144Ce - 144Pr antineutrino source to be deployed in the Kamioka Liquid Scintillator Anti-Neutrino Detector (KamLAND). KamLAND's 13m diameter target volume provides a suitable environment to measure energy and position dependence of the detected neutrino flux. A characteristic oscillation pattern would be visible for a baseline of about 10 m or less, providing a very clean signal of neutrino disappearance into a yet-unknown, "sterile" state. Such a measurement will be free of any reactor-related uncertainties. After 1.5 years of data taking the Reactor Antineutrino Anomaly parameter space will be tested at > 95% C.L.Comment: White paper prepared for Snowmass-2013; slightly different author lis

Changes in catastrophic health expenditure in post-conflict Sierra Leone: an Oaxaca-blinder decomposition analysis.

BACKGROUND: At the end of the eleven-year conflict in Sierra Leone, a wide range of policies were implemented to address both demand- and supply-side constraints within the healthcare system, which had collapsed during the conflict. This study examines the extent to which households' exposure to financial risks associated with seeking healthcare evolved in post-conflict Sierra Leone. METHOD: This study uses the 2003 and 2011 cross-sections of the Sierra Leone Integrated Household Survey to examine changes in catastrophic health expenditure between 2003 and 2011. An Oaxaca-Blinder decomposition approach is used to quantify the extent to which changes in catastrophic health expenditure are attributable to changes in the distribution of determinants (distributional effect) and to changes in the impact of these determinants on the probability of incurring catastrophic health expenditure (coefficient effect). RESULTS: The incidence of catastrophic health expenditure decreased significantly by 18% from approximately 50% in 2003 t0 32% in 2011. The decomposition analysis shows that this decrease represents net effects attributable to the distributional and coefficient effects of three determinants of catastrophic health expenditure - ill-health, the region in which households reside and the type of health facility used. A decrease in the incidence of ill-health and changes in the regional location of households contributed to a decrease in catastrophic health expenditure. The distributional effect of health facility types observed as an increase in the use of public health facilities, and a decrease in the use of services in facilities owned by non-governmental organizations (NGOs) also contributed to a decrease in the incidence of catastrophic health expenditure. However, the coefficient effect of public health facilities and NGO-owned facilities suggests that substantial exposure to financial risk remained for households utilizing both types of health facilities in 2011. CONCLUSION: The findings support the need to continue expanding current demand-side policies in Sierra Leone to reduce the financial risk of exposure to ill health

Minimal residual disease in Myeloma: Application for clinical care and new drug registration

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes

FACT, the Bur Kinase Pathway, and the Histone Co-Repressor HirC Have Overlapping Nucleosome-Related Roles in Yeast Transcription Elongation

Gene transcription is constrained by the nucleosomal nature of chromosomal DNA. This nucleosomal barrier is modulated by FACT, a conserved histone-binding heterodimer. FACT mediates transcription-linked nucleosome disassembly and also nucleosome reassembly in the wake of the RNA polymerase II transcription complex, and in this way maintains the repression of ‘cryptic’ promoters found within some genes. Here we focus on a novel mutant version of the yeast FACT subunit Spt16 that supplies essential Spt16 activities but impairs transcription-linked nucleosome reassembly in dominant fashion. This Spt16 mutant protein also has genetic effects that are recessive, which we used to show that certain Spt16 activities collaborate with histone acetylation and the activities of a Bur-kinase/Spt4–Spt5/Paf1C pathway that facilitate transcription elongation. These collaborating activities were opposed by the actions of Rpd3S, a histone deacetylase that restores a repressive chromatin environment in a transcription-linked manner. Spt16 activity paralleling that of HirC, a co-repressor of histone gene expression, was also found to be opposed by Rpd3S. Our findings suggest that Spt16, the Bur/Spt4–Spt5/Paf1C pathway, and normal histone abundance and/or stoichiometry, in mutually cooperative fashion, facilitate nucleosome disassembly during transcription elongation. The recessive nature of these effects of the mutant Spt16 protein on transcription-linked nucleosome disassembly, contrasted to its dominant negative effect on transcription-linked nucleosome reassembly, indicate that mutant FACT harbouring the mutant Spt16 protein competes poorly with normal FACT at the stage of transcription-linked nucleosome disassembly, but effectively with normal FACT for transcription-linked nucleosome reassembly. This functional difference is consistent with the idea that FACT association with the transcription elongation complex depends on nucleosome disassembly, and that the same FACT molecule that associates with an elongation complex through nucleosome disassembly is retained for reassembly of the same nucleosome

Effective control of sars-cov-2 transmission between healthcare workers during a period of diminished community prevalence of covid-19

Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to nearzero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely