Nanoscopic Interfacial Hydrogel Viscoelasticity Revealed from Comparison of Macroscopic and Microscopic Rheology

Deviations between macrorheological and particle-based microrheological measurements are often considered to be a nuisance and neglected. We study aqueous poly(ethylene oxide) (PEO) hydrogels for varying PEO concentrations and chain lengths that contain microscopic tracer particles and show that these deviations reveal the nanoscopic viscoelastic properties of the particle–hydrogel interface. Based on the transient Stokes equation, we first demonstrate that the deviations are not due to finite particle radius, compressibility, or surface-slip effects. Small-angle neutron scattering rules out hydrogel heterogeneities. Instead, we show that a generalized Stokes–Einstein relation, accounting for an interfacial shell around tracers with viscoelastic properties that deviate from bulk, consistently explains our macrorheological and microrheological measurements. The extracted shell diameter is comparable to the PEO end-to-end distance, indicating the importance of dangling chain ends. Our methodology reveals the nanoscopic interfacial rheology of hydrogels and is applicable to different kinds of viscoelastic fluids and particles

ATAMM enhancement and multiprocessor performance evaluation

ATAMM (Algorithm To Architecture Mapping Model) enhancement and multiprocessor performance evaluation is discussed. The following topics are included: the ATAMM model; ATAMM enhancement; ADM (Advanced Development Model) implementation of ATAMM; and ATAMM support tools

Saxagliptin clinical trials: evaluation of CV risk

Diabetes is Australia's fastest growing chronic disease with approximately 890,000 patients currently diagnosed with diabetes. 1 By 2031 it is predicted that 3.3 million Australians will have type 2 diabetes mellitus, 2 thus increasing the demand for treatment. However, several diabetes, obesity, and lipid drug trials have had unexpected and unfavourable cardiovascular (CV) results. The saxagliptin (SAXA) phase 2b/3 program enrolled a range of patients with diabetes and included a controlled, long-term safety extension phase. SAXA is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor. In the SAXA clinical data, the primary endpoint, major adverse cardiovascular events (MACE; stroke, myocardial infarction or CV death, analysed post hoc) and acute cardiovascular events (ACE; acute, clinically significant events, including cardiac revascularisation procedures) were identified using selected MedDRA Preferred Terms. CV events were analysed in a comprehensive dataset: 8 randomised, double-blind, phase 2b/3 trials, which included 4607 patients (3206 randomised to SAXA 2.5, 5, or 10 mg; 150 randomised to SAXA 20, 40, or 100 mg; and 1251 randomised to placebo, metformin, or up-titrated glyburide). Overall exposure was 3758 patient-years on SAXA and 1293 patient-years on comparators. Within the SAXA population, 81% had at least 1 CV risk factor in addition to diabetes, with hypertension (52%), dyslipidaemia (44%), or history of smoking (39%) the most common; 12% had known prior CV disease. Comparator group had similar proportions. Numbers of patients with events are shown in Table. The Cox proportional hazard ratio for MACE was 0.44 (95% CI: 0.24–0.82) and for ACE was 0.59 (95% CI: 0.35–1.00). A series of sensitivity analyses using related endpoints and alternative analytic methods produced consistent results. Based on a >5000 patient-year clinical trial experience, there was no evidence of increased CV risk with SAXA treatment ― as monotherapy or in combination with other oral antidiabetic agents. These data raise the hypothesis of a cardioprotective effect of SAXA, which will be studied in the SAVOR trial

What makes automated systems tick?

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High variability within pet foods prevents the identification of native species in pet cats' diets using isotopic evaluation

Domestic cats preying on wildlife is a frequent conservation concern but typical approaches for assessing impacts rely on owner reports of prey returned home, which can be biased by inaccurate reporting or by cats consuming prey instead of bringing it home. Isotopes offer an alternative way to quantify broad differences in animal diets. By obtaining samples of pet food from cat owners we predicted that we would have high power to identify cats feeding on wild birds or mammals, given that pet food is thought to have higher C isotope values, due to the pervasive use of corn and/or corn by-products as food ingredients, than native prey. We worked with citizen scientists to quantify the isotopes of 202 cat hair samples and 239 pet food samples from the US and UK. We also characterized the isotopes of 11 likely native prey species from the southeastern US and used mixing models to assess the diet of 47 cats from the same region. Variation in C and N isotope values for cat food was very high, even within the same brand/flavor, suggesting that pet food manufacturers use a wide range of ingredients, and that these may change over time. Cat food and cat hair from the UK had lower C values than the US, presumably reflecting differences in the amount of corn used in the food chains of the two countries. This high variation in pet food reduced our ability to classify cats as hunters of native prey, such that only 43% of the animals could be confidently assigned. If feral or free ranging cats were considered, this uncertainty would be even higher as pet food types would be unknown. Our results question the general assumption that anthropogenic foods always have high C isotope values, because of the high variability we documented within one product type (cat food) and between countries (US vs. UK), and emphasize the need to test a variety of standards before making conclusions from isotope ecology studies

In Memoriam: Professor Emeritus Richard O. Kummert

The Washington Law Review dedicates its October 2012 issue to Professor Richard O. Kummert who passed away last April at the age of seventy-nine. Professor Kummert served as the faculty advisor to the Washington Law Review for over four decades. The success of this publication owes, in many ways, to Professor Kummert\u27s steadfast guidance. The following memorial remarks come from his former students, colleagues, and friends. Many, but not all, of these remarks have been graciously adapted from speeches given at Professor Kummert\u27s memorial service, which was held at the University of Washington School of Law on April 29, 2012

A single nephron model of acute tubular injury: Role of tubuloglomerular feedback

A single nephron model of acute tubular injury: Role of tubuloglomerular feedback. A single nephron model of nephrotoxic tubular injury was established to examine the mechanism whereby acute tubular damage contributes to reductions in nephron filtration rate (SNGFR). Acute microperfusion of 0.5ng of uranyl nitrate (UN) into the early proximal tubule produced a significant reduction (16 to 30%) in SNGFR measured in both distal and proximal tubules of the same nephron and a decrease in absolute proximal reabsorption. Microperfused inulin was retained in the tubule suggesting this finding reflected a true reduction in SNGFR. Concurrent infusion of high dose furosemide (2 × 10-4M) and bumetanide (2 × 10-5M), but not low dose furosemide (2 × 10-5M), prevented the UN induced reduction in SNGFR. High dose furosemide begun after UN perfusion also prevented reduction in SNGFR. Continuous direct measurement of glomerular capillary hydrostatic pressure revealed no change. Distal intratubular Na+ and CI- concentration increased significantly after UN perfusion. Activation of tubuloglomerular feedback mechanisms best explains the reduction in glomerular ultrafiltration that is characteristic of nephrotoxic forms of tubular injury

Initial severity of depression and efficacy of cognitive-behavioural therapy: individual-participant data meta-analysis of pill-placebo-controlled trials

BACKGROUND: The influence of baseline severity has been examined for antidepressant medications but has not been studied properly for cognitive-behavioural therapy (CBT) in comparison with pill placebo. AIMS: To synthesise evidence regarding the influence of initial severity on efficacy of CBT from all randomised controlled trials (RCTs) in which CBT, in face-to-face individual or group format, was compared with pill-placebo control in adults with major depression. METHOD: A systematic review and an individual-participant data meta-analysis using mixed models that included trial effects as random effects. We used multiple imputation to handle missing data. RESULTS: We identified five RCTs, and we were given access to individual-level data (n = 509) for all five. The analyses revealed that the difference in changes in Hamilton Rating Scale for Depression between CBT and pill placebo was not influenced by baseline severity (interaction P = 0.43). Removing the non-significant interaction term from the model, the difference between CBT and pill placebo was a standardised mean difference of -0.22 (95% CI -0.42 to -0.02, P = 0.03, I2 = 0%). CONCLUSIONS: Patients suffering from major depression can expect as much benefit from CBT across the wide range of baseline severity. This finding can help inform individualised treatment decisions by patients and their clinicians.R01 MH060998 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R01 AT007257 - NCCIH NIH HHS; R21 MH101567 - NIMH NIH HHS; K02 MH001697 - NIMH NIH HHS; R01 MH060713 - NIMH NIH HHS; R34 MH099311 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; K23 MH100259 - NIMH NIH HHS; R01 MH099021 - NIMH NIH HH

Human Adaptability for Deep Space Missions: An Exploratory Study

The present qualitative study conducts in-depth interviews with astronauts and other subject matter experts in order to shed light on human adaptability in extreme environments. Deep space travel will entail a range of highly stressful conditions to which astronauts must adapt. Feelings of isolation will be increased, as the space traveler is farther from Earth for longer periods of time. Daily life will take place in small and confined areas, for durations extending into years. The dangers of the extreme environment of space are ever-present, and failure of critical equipment or components can lead to death. Astronauts will need to function more autonomously, with diminished support from Earth. It is thus important to select and train future astronauts who are able to adapt to such extreme and variable conditions and continue to function effectively. Subject matter experts identify the central adaptive challenges faced by crewmembers, and what are the key individual attributes associated with human adaptability. Results also point to organizational factors, as well as several coping and resource strategies that can be applied to improve human adaptability to extreme environments and missions. These results can be used to inform selection and training programs, as well as the design of space vehicles, systems, and habitats in order to enhance astronaut adaptive task performance