Forecasting Proximal Femur and Wrist Fracture Caused by a Fall to the Side during Space Exploration Missions to the Moon and Mars

The possibility of bone fracture in space is a concern due to the negative impact it could have on a mission. The Bone Fracture Risk Module (BFxRM) developed at the NASA Glenn Research Center is a statistical simulation that quantifies the probability of bone fracture at specific skeletal locations for particular activities or events during space exploration missions. This paper reports fracture probability predictions for the proximal femur and wrist resulting from a fall to the side during an extravehicular activity (EVA) on specific days of lunar and Martian exploration missions. The risk of fracture at the proximal femur on any given day of the mission is small and fairly constant, although it is slightly greater towards the end of the mission, due to a reduction in proximal femur bone mineral density (BMD). The risk of wrist fracture is greater than the risk of hip fracture and there is an increased risk on Mars since it has a higher gravitational environment than the moon. The BFxRM can be used to help manage the risk of bone fracture in space as an engineering tool that is used during mission operation and resource planning

The Extravehicular Suit Impact Load Attenuation Study for Use in Astronaut Bone Fracture Prediction

The NASA Integrated Medical Model (IMM) assesses the risk, including likelihood and impact of occurrence, of all credible in-flight medical conditions. Fracture of the proximal femur is a traumatic injury that would likely result in loss of mission if it were to happen during spaceflight. The low gravity exposure causes decreases in bone mineral density which heightens the concern. Researchers at the NASA Glenn Research Center have quantified bone fracture probability during spaceflight with a probabilistic model. It was assumed that a pressurized extravehicular activity (EVA) suit would attenuate load during a fall, but no supporting data was available. The suit impact load attenuation study was performed to collect analogous data. METHODS: A pressurized EVA suit analog test bed was used to study how the offset, defined as the gap between the suit and the astronaut s body, impact load magnitude and suit operating pressure affects the attenuation of impact load. The attenuation data was incorporated into the probabilistic model of bone fracture as a function of these factors, replacing a load attenuation value based on commercial hip protectors. RESULTS: Load attenuation was more dependent on offset than on pressurization or load magnitude, especially at small offsets. Load attenuation factors for offsets between 0.1 - 1.5 cm were 0.69 +/- 0.15, 0.49 +/- 0.22 and 0.35 +/- 0.18 for mean impact forces of 4827, 6400 and 8467 N, respectively. Load attenuation factors for offsets of 2.8 - 5.3 cm were 0.93 +/- 0.2, 0.94 +/- 0.1 and 0.84 +/- 0.5, for the same mean impact forces. Reductions were observed in the 95th percentile confidence interval of the bone fracture probability predictions. CONCLUSIONS: The reduction in uncertainty and improved confidence in bone fracture predictions increased the fidelity and credibility of the fracture risk model and its benefit to mission design and operational decisions

Instantons on ALE spaces and orbifold partitions

We consider N=4 theories on ALE spaces of $A_{k-1}$ type. As is well known, their partition functions coincide with $A_{k-1}$ affine characters. We show that these partition functions are equal to the generating functions of some peculiar classes of partitions which we introduce under the name 'orbifold partitions'. These orbifold partitions turn out to be related to the generalized Frobenius partitions introduced by G. E. Andrews some years ago. We relate the orbifold partitions to the blended partitions and interpret explicitly in terms of a free fermion system.Comment: 28 pages, 10 figures; reference adde

Hepatic profile analyses of tipranavir in Phase II and III clinical trials

<p>Abstract</p> <p>Background</p> <p>The risk and course of serum transaminase elevations (TEs) and clinical hepatic serious adverse event (SAE) development in ritonavir-boosted tipranavir (TPV/r) 500/200 mg BID recipients, who also received additional combination antiretroviral treatment agents in clinical trials (TPV/r-based cART), was determined.</p> <p>Methods</p> <p>Aggregated transaminase and hepatic SAE data through 96 weeks of TPV/r-based cART from five Phase IIb/III trials were analyzed. Patients were categorized by the presence or absence of underlying liver disease (+LD or -LD). Kaplan-Meier (K-M) probability estimates for time-to-first US National Institutes of Health, Division of AIDS (DAIDS) Grade 3/4 TE and clinical hepatic SAE were determined and clinical actions/outcomes evaluated. Risk factors for DAIDS Grade 3/4 TE were identified through multivariate Cox regression statistical modeling.</p> <p>Results</p> <p>Grade 3/4 TEs occurred in 144/1299 (11.1%) patients; 123/144 (85%) of these were asymptomatic; 84% of these patients only temporarily interrupted treatment or continued, with transaminase levels returning to Grade ≤ 2. At 96 weeks of study treatment, the incidence of Grade 3/4 TEs was higher among the +LD (16.8%) than among the -LD (10.1%) patients. K-M analysis revealed an incremental risk for developing DAIDS Grade 3/4 TEs; risk was greatest through 24 weeks (6.1%), and decreasing thereafter (>24-48 weeks: 3.4%, >48 weeks-72 weeks: 2.0%, >72-96 weeks: 2.2%), and higher in +LD than -LD patients at each 24-week interval. Treatment with TPV/r, co-infection with hepatitis B and/or C, DAIDS grade >1 TE and CD4⁺> 200 cells/mm³at baseline were found to be independent risk factors for development of DAIDS Grade 3/4 TE; the hazard ratios (HR) were 2.8, 2.0, 2.1 and 1.5, respectively. Four of the 144 (2.7%) patients with Grade 3/4 TEs developed hepatic SAEs; overall, 14/1299 (1.1%) patients had hepatic SAEs including six with hepatic failure (0.5%). The K-M risk of developing hepatic SAEs through 96 weeks was 1.4%; highest risk was observed during the first 24 weeks and decreased thereafter; the risk was similar between +LD and -LD patients for the first 24 weeks (0.6% and 0.5%, respectively) and was higher for +LD patients, thereafter.</p> <p>Conclusion</p> <p>Through 96 weeks of TPV/r-based cART, DAIDS Grade 3/4 TEs and hepatic SAEs occurred in approximately 11% and 1% of TPV/r patients, respectively; most (84%) had no significant clinical implications and were managed without permanent treatment discontinuation. Among the 14 patients with hepatic SAE, 6 experienced hepatic failure (0.5%); these patients had profound immunosuppression and the rate appears higher among hepatitis co-infected patients. The overall probability of experiencing a hepatic SAE in this patient cohort was 1.4% through 96 weeks of treatment. Independent risk factors for DAIDS Grade 3/4 TEs include TPV/r treatment, co-infection with hepatitis B and/or C, DAIDS grade >1 TE and CD4⁺> 200 cells/mm³at baseline.</p> <p>Trial registration</p> <p>US-NIH Trial registration number: NCT00144170</p

Dideoxynucleoside HIV reverse transcriptase inhibitors and drug-related hepatotoxicity: a case report

This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis). A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage

We know DAAs work, so now what?:Simplifying models of care to enhance the hepatitis C cascade

Globally, some 71 million people are chronically infected with hepatitis C virus (HCV). Marginalised populations, particularly people who inject drugs (PWID), have low testing, linkage-to-care and treatment rates for HCV. Several models of care (MoCs) and service delivery interventions have the potential to improve outcomes across the HCV cascade of care, but much of the relevant research was carried out when interferon-based treatment was the standard of care. Often it was not practical to scale up these earlier models and interventions because the clinical care needs of patients taking interferon-based regimens imposed too much of a financial and human resource burden on health systems. Despite the adoption of highly effective, all-oral direct-acting antiviral (DAA) therapies in recent years, approaches to HCV testing and treatment have evolved slowly and often remain rooted in earlier paradigms. The effectiveness of DAAs allows for simpler approaches and has encouraged countries where the drugs are widely available to set their sights on the ambitious World Health Organization (WHO) HCV elimination targets. Since a large proportion of chronically HCV-infected people are not currently accessing treatment, there is an urgent need to identify and implement existing simplified MoCs that speak to specific populations' needs. This article aims to: 1) review the evidence on MoCs for HCV; and 2) distil the findings into recommendations for how stakeholders can simplify the path taken by chronically HCV-infected individuals from testing to cure and subsequent care and monitoring

ABJM theory as a Fermi gas

The partition function on the three-sphere of many supersymmetric Chern-Simons-matter theories reduces, by localization, to a matrix model. We develop a new method to study these models in the M-theory limit, but at all orders in the 1/N expansion. The method is based on reformulating the matrix model as the partition function of an ideal Fermi gas with a non-trivial, one-particle quantum Hamiltonian. This new approach leads to a completely elementary derivation of the N^{3/2} behavior for ABJM theory and N=3 quiver Chern-Simons-matter theories. In addition, the full series of 1/N corrections to the original matrix integral can be simply determined by a next-to-leading calculation in the WKB or semiclassical expansion of the quantum gas, and we show that, for several quiver Chern-Simons-matter theories, it is given by an Airy function. This generalizes a recent result of Fuji, Hirano and Moriyama for ABJM theory. It turns out that the semiclassical expansion of the Fermi gas corresponds to a strong coupling expansion in type IIA theory, and it is dual to the genus expansion. This allows us to calculate explicitly non-perturbative effects due to D2-brane instantons in the AdS background.Comment: 52 pages, 11 figures. v3: references, corrections and clarifications added, plus a footnote on the relation to the recent work by Hanada et a

Direct Integration and Non-Perturbative Effects in Matrix Models

We show how direct integration can be used to solve the closed amplitudes of multi-cut matrix models with polynomial potentials. In the case of the cubic matrix model, we give explicit expressions for the ring of non-holomorphic modular objects that are needed to express all closed matrix model amplitudes. This allows us to integrate the holomorphic anomaly equation up to holomorphic modular terms that we fix by the gap condition up to genus four. There is an one-dimensional submanifold of the moduli space in which the spectral curve becomes the Seiberg--Witten curve and the ring reduces to the non-holomorphic modular ring of the group $\Gamma(2)$. On that submanifold, the gap conditions completely fix the holomorphic ambiguity and the model can be solved explicitly to very high genus. We use these results to make precision tests of the connection between the large order behavior of the 1/N expansion and non-perturbative effects due to instantons. Finally, we argue that a full understanding of the large genus asymptotics in the multi-cut case requires a new class of non-perturbative sectors in the matrix model.Comment: 51 pages, 8 figure

High Prevalence and Genetic Diversity of HCV among HIV-1 Infected People from Various High-Risk Groups in China

BACKGROUND: Co-infection with HIV-1 and HCV is a significant global public health problem and a major consideration for anti-HIV-1 treatment. HCV infection among HIV-1 positive people who are eligible for the newly launched nationwide anti-HIV-1 treatment program in China has not been well characterized. METHODOLOGY: A nationwide survey of HIV-1 positive injection drug uses (IDU), former paid blood donors (FBD), and sexually transmitted cases from multiple provinces including the four most affected provinces in China was conducted. HCV prevalence and genetic diversity were determined. We found that IDU and FBD have extremely high rates of HCV infection (97% and 93%, respectively). Surprisingly, people who acquired HIV-1 through sexual contact also had a higher rate of HCV infection (20%) than the general population. HIV-1 subtype and HCV genotypes were amazingly similar among FBD from multiple provinces stretching from Central to Northeast China. However, although patterns of overland trafficking of heroin and distinct HIV-1 subtypes could be detected among IDU, HCV genotypes of IDU were more diverse and exhibited significant regional differences. CONCLUSION: Emerging HIV-1 and HCV co-infection and possible sexual transmission of HCV in China require urgent prevention measures and should be taken into consideration in the nationwide antiretroviral treatment program