Statistically robust representation and comparison of mortality profiles in archaeozoology

Archaeozoological mortality profiles have been used to infer site-specific subsistence strategies. There is however no common agreement on the best way to present these profiles and confidence intervals around age class proportions. In order to deal with these issues, we propose the use of the Dirichlet distribution and present a new approach to perform age-at-death multivariate graphical comparisons. We demonstrate the efficiency of this approach using domestic sheep/goat dental remains from 10 Cardial sites (Early Neolithic) located in South France and the Iberian Peninsula. We show that the Dirichlet distribution in age-at-death analysis can be used: (i) to generate Bayesian credible intervals around each age class of a mortality profile, even when not all age classes are observed; and (ii) to create 95% kernel density contours around each age-at-death frequency distribution when multiple sites are compared using correspondence analysis. The statistical procedure we present is applicable to the analysis of any categorical count data and particularly well-suited to archaeological data (e.g. potsherds, arrow heads) where sample sizes are typically small

Biomedical Support of U.S. Extravehicular Activity

The world's first extravehicular activity (EVA) was performed by A. A. Leonov on March 18, 1965 during the Russian Voskhod-2 mission. The first US EVA was executed by Gemini IV astronaut Ed White on June 3, 1965, with an umbilical tether that included communications and an oxygen supply. A hand-held maneuvering unit (HHMU) also was used to test maneuverability during the brief EVA; however the somewhat stiff umbilical limited controlled movement. That constraint, plus difficulty returning through the vehicle hatch, highlighted the need for increased thermal control and improved EVA ergonomics. Clearly, requirements for a useful EVA were interrelated with the vehicle design. The early Gemini EVAs generated requirements for suits providing micro-meteor protection, adequate visual field and eye protection from solar visual and infrared radiation, gloves optimized for dexterity while pressurized, and thermal systems capable of protecting the astronaut while rejecting metabolic heat during high workloads. Subsequent Gemini EVAs built upon this early experience and included development of a portable environmental control and life support systems (ECLSS) and an astronaut maneuvering unit. The ECLSS provided a pressure vessel and controller with functional control over suit pressure, oxygen flow, carbon dioxide removal, humidity, and temperature control. Gemini EVA experience also identified the usefulness of underwater neutral buoyancy and altitude chamber task training, and the importance of developing reliable task timelines. Improved thermal management and carbon dioxide control also were required for high workload tasks. With the Apollo project, EVA activity was primarily on the lunar surface; and suit durability, integrated liquid cooling garments, and low suit operating pressures (3.75 pounds per square inch absolute [psia] or 25.8 kilopascal [kPa],) were required to facilitate longer EVAs with ambulation and significant physical workloads with average metabolic rates of 1000 BTU/hr and peaks of up to 2200 BTU/hr. Mobility was further augmented with the Lunar Roving Vehicle. The Apollo extravehicular mobility unit (EMU) was made up of over 15 components, ranging from a biomedical belt for capturing and transmitting biomedical data, urine and fecal containment systems, a liquid cooling garment, communications cap, a modular portable life support system (PLSS), a boot system, thermal overgloves, and a bubble helmet with eye protection. Apollo lunar astronauts performed successful EVAs on the lunar surface from a 5 psia (34.4 kPa) 100% oxygen environment in the Lunar Lander. A maximum of three EVAs were performed on any mission. For Skylab a modified A7LB suit, used for Apollo 15, was selected. The Skylab astronaut life support assembly (ALSA) provided umbilical support through the life support umbilical (LSU) and used open loop oxygen flow, rather than closed-loop as in Apollo missions. Thermal control was provided by liquid water circulated by spacecraft pumps and electrical power also was provided from the spacecraft via the umbilical. The cabin atmosphere of 5 psia (34.4 kPa), 70% oxygen, provided a normoxic atmosphere and because of the very low nitrogen partial pressures, no special protocols were required to protect against decompression sickness (DCS) as was the case with the Apollo spacecraft with a 5 psi, 100% oxygen environment

CFHTLenS: the environmental dependence of galaxy halo masses from weak lensing

We use weak gravitational lensing to analyse the dark matter haloes around satellite galaxies in galaxy groups in the Canada–France–Hawaii Telescope Lensing Survey (CFHTLenS) data set. This data set is derived from the Canada–France–Hawaii Telescope Legacy Survey Wide survey, and encompasses 154 deg^2 of high-quality shape data. Using the photometric redshifts, we divide the sample of lens galaxies with stellar masses in the range 10^(9)–10^(10.5) M_⊙ into those likely to lie in high-density environments (HDE) and those likely to lie in low-density environments (LDE). Through comparison with galaxy catalogues extracted from the Millennium Simulation, we show that the sample of HDE galaxies should primarily (∼61 per cent) consist of satellite galaxies in groups, while the sample of LDE galaxies should consist of mostly (∼87 per cent) non-satellite (field and central) galaxies. Comparing the lensing signals around samples of HDE and LDE galaxies matched in stellar mass, the lensing signal around HDE galaxies clearly shows a positive contribution from their host groups on their lensing signals at radii of ∼500–1000 kpc, the typical separation between satellites and group centres. More importantly, the subhaloes of HDE galaxies are less massive than those around LDE galaxies by a factor of 0.65 ± 0.12, significant at the 2.9σ level. A natural explanation is that the haloes of satellite galaxies are stripped through tidal effects in the group environment. Our results are consistent with a typical tidal truncation radius of ∼40 kpc

MultiSig: a new high-precision approach to the analysis of complex biomolecular systems

MultiSig is a newly developed mode of analysis of sedimentation equilibrium (SE) experiments in the analytical ultracentrifuge, having the capability of taking advantage of the remarkable precision (~0.1 % of signal) of the principal optical (fringe) system employed, thus supplanting existing methods of analysis through reducing the ‘noise’ level of certain important parameter estimates by up to orders of magnitude. Long-known limitations of the SE method, arising from lack of knowledge of the true fringe number in fringe optics and from the use of unstable numerical algorithms such as numerical differentiation, have been transcended. An approach to data analysis, akin to ‘spatial filtering’, has been developed, and shown by both simulation and practical application to be a powerful aid to the precision with which near-monodisperse systems can be analysed, potentially yielding information on protein-solvent interaction. For oligo- and poly-disperse systems the information returned includes precise average mass distributions over both cell radial and concentration ranges and mass-frequency histograms at fixed radial positions. The application of MultiSig analysis to various complex heterogenous systems and potentially multiply-interacting carbohydrate oligomers is described

Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

A Single Amino Acid Mutation in SNAP-25 Induces Anxiety-Related Behavior in Mouse

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC) phosphorylates Ser187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser187 of SNAP-25 with Ala using “knock-in” technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

β-alanine supplementation improves in-vivo fresh and fatigued skeletal muscle relaxation speed

Purpose: In fresh muscle, supplementation with the rate-limiting precursor of carnosine, β-alanine (BA), results in a decline in muscle half-relaxation time (HRT) potentially via alterations to calcium (Ca2+) handling. Accumulation of hydrogen cation (H+) has been shown to impact Ca2+ signalling during muscular contraction, carnosine has the potential to serve as a cytoplasmic regulator of Ca2+ and H+ coupling, since it binds to both ions. The present study examined the effect of BA supplementation on intrinsic in-vivo isometric knee extensor force production and muscle contractility in both fresh and fatigued human skeletal muscle assessed during voluntary and electrically evoked (nerve and superficial muscle stimulation) contractions. Methods: Twenty-three males completed two experimental sessions, pre- and post- 28 day supplementation with 6.4 g.day−1 of BA (n=12) or placebo (PLA; n=11). Isometric force was recorded during a series of voluntary and electrically evoked knee extensor contractions. Results: BA supplementation had no effect on voluntary or electrically  evoked isometric force production, or twitch electromechanical delay and time-to-peak tension. There was a significant decline in muscle HRT in fresh and fatigued muscle conditions  during both resting (3±13%; 19±26%) and potentiated (1±15%; 2±20%) twitch contractions. Conclusions: The mechanism for reduced HRT in fresh and fatigued skeletal muscle following BA supplementation is unclear. Due to the importance of muscle relaxation on total energy consumption, especially during short, repeated contractions, BA supplementation may prove to be beneficial in minimising contractile slowing induced by fatigue. Trial registration The trial is registered with Clinicaltrials.gov, ID number NCT02819505