Monitoring changes in skin temperature associated with exercise in horses on a water treadmill by use of infrared thermography

Infrared thermography (IRT) was used to assess surface temperature change as an indirect measure of muscle activity and exercise associated changes in blood flow in the working hind limb muscles of horses (n¼7) undergoing water tread mill exercise. Three treatments were investigated including the treadmill ran dry (TD), water at the height of the proximal interphalangeal joint (PIP) and water at the height of the carpus (CP). Maximum skin surface temperature was recorded from the region of these mitendinosus muscle during exercise at each water height. There was a significant difference in surface hind limb temperature between exercise on the water treadmill ran dry and with water at the height of the PIP and CP (Po0.0001) with hotter temperatures recorded during the TD treatment. There was a greater increase in surface temperature of the hind limbs from preexercise to maximum temperature during the PIP and CP treatments when compared to the TD treatment, however, this was not significant (P¼0.58). There was no significant difference in surface hind limb temperature found between exercise in water at the height of the PIP and water at the height of the CP. The findings from this study suggest that IRT is able to non-invasively detect muscle activity and associated changes in blood flow whilst horses are exercised on a water treadmill. IRT could potentially be used as an alternative method to assess muscle activity and temperature change in an aquatic environment where existing methods present methodological challenges

Probing the X-Ray Binary Populations of the Ring Galaxy NGC 1291

We present Chandra studies of the X-ray binary (XRB) populations in the bulge and ring regions of the ring galaxy NGC 1291. We detect 169 X-ray point sources in the galaxy, 75 in the bulge and 71 in the ring, utilizing the four available Chandra observations totaling an effective exposure of 179 ks. We report photometric properties of these sources in a point-source catalog. There are ~40% of the bulge sources and ~25% of the ring sources showing >3\sigma long-term variability in their X-ray count rate. The X-ray colors suggest that a significant fraction of the bulge (~75%) and ring (~65%) sources are likely low-mass X-ray binaries (LMXBs). The spectra of the nuclear source indicate that it is a low-luminosity AGN with moderate obscuration; spectral variability is observed between individual observations. We construct 0.3-8.0 keV X-ray luminosity functions (XLFs) for the bulge and ring XRB populations, taking into account the detection incompleteness and background AGN contamination. We reach 90% completeness limits of ~1.5\times10^{37} and ~2.2\times10^{37} erg/s for the bulge and ring populations, respectively. Both XLFs can be fit with a broken power-law model, and the shapes are consistent with those expected for populations dominated by LMXBs. We perform detailed population synthesis modeling of the XRB populations in NGC 1291, which suggests that the observed combined XLF is dominated by an old LMXB population. We compare the bulge and ring XRB populations, and argue that the ring XRBs are associated with a younger stellar population than the bulge sources, based on the relative overdensity of X-ray sources in the ring, the generally harder X-ray color of the ring sources, the overabundance of luminous sources in the combined XLF, and the flatter shape of the ring XLF.Comment: 15 pages, 11 figures. Accepted for publication in Ap

Treatment for inclusion body myositis

Background Inclusion body myositis (IBM) is a late‐onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects of treatment for IBM. Search methods On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials. Selection criteria We considered randomised or quasi‐randomised trials, including cross‐over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews. Data collection and analysis We used standard Cochrane methodological procedures. Main results The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta‐1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) ‐0.06, 95% CI ‐0.15 to 0.03) between IFN beta‐1a and placebo (moderate‐quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate‐quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low‐quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta‐analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re‐analysis. Other comparisons were also reported in single trials. An open trial of anti‐T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low‐quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events. Authors' conclusions Trials of interferon beta‐1a and MTX provided moderate‐quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low‐quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures

The Southwest Pacific Ocean circulation and climate experiment (SPICE) : report to CLIVAR SSG

The Southwest Pacific Ocean Circulation and Climate Experiment (SPICE) is an international research program under the auspices of CLIVAR. The key objectives are to understand the Southwest Pacific Ocean circulation and the South Pacific Convergence Zone (SPCZ) dynamics, as well as their influence on regional and basin-scale climate patterns. South Pacific thermocline waters are transported in the westward flowing South Equatorial Current (SEC) toward Australia and Papua-New Guinea. On its way, the SEC encounters the numerous islands and straits of the Southwest Pacific and forms boundary currents and jets that eventually redistribute water to the equator and high latitudes. The transit in the Coral, Solomon, and Tasman Seas is of great importance to the climate system because changes in either the temperature or the amount of water arriving at the equator have the capability to modulate the El Nino-Southern Oscillation, while the southward transports influence the climate and biodiversity in the Tasman Sea. After 7 years of substantial in situ oceanic observational and modeling efforts, our understanding of the region has much improved. We have a refined description of the SPCZ behavior, boundary currents, pathways, and water mass transformation, including the previously undocumented Solomon Sea. The transports are large and vary substantially in a counter-intuitive way, with asymmetries and gating effects that depend on time scales. This paper provides a review of recent advancements and discusses our current knowledge gaps and important emerging research directions

The entrepreneurial marketing management and commercialization arrangements of born-global bio-enterprises: the case of UK companies

Born global bio-enterprises are a unique “breed” of relatively small biotechnology enterprises operating in multiple countries. The companies are nimble and seemingly well-prepared for challenges that ephemeral markets such as the internationalised biotechnology sector brings. The international marketing management challenges they encounter appear to stimulate their entrepreneurial marketing and commercialisation instincts. Surprisingly, there is a dearth of studies that examine their entrepreneurial predispositions. As such, this study is an attempt to explain their entrepreneurial tendencies by investigating the marketing and commercialisation strategies adopted by born global bio-enterprises in the UK’s biotechnology industry. The study assumes a multi-case approach examining five archetypical born global bio-enterprises currently active in the UK. It contributes to the international entrepreneurship and marketing management literature. Specifically, it provides international business managers with new knowledge about various marketing manoeuvres they can apply in international networks for their marketing mileage. In doing so, the study proposes a theoretical framework mapping out entrepreneurial marketing and commercialisation arrangements in internationalised biotechnology markets. Its findings are useful to various stakeholders including: policy makers, managers of technology-based companies and business management researchers

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

ACCESS-OM2 v1.0: a global ocean-sea ice model at three resolutions

We introduce ACCESS-OM2, a new version of the ocean–sea ice model of the Australian Community Climate and Earth System Simulator. ACCESS-OM2 is driven by a prescribed atmosphere (JRA55-do) but has been designed to form the ocean–sea ice component of the fully coupled (atmosphere–land–ocean–sea ice) ACCESS-CM2 model. Importantly, the model is available at three different horizontal resolutions: a coarse resolution (nominally 1∘ horizontal grid spacing), an eddy-permitting resolution (nominally 0.25∘), and an eddy-rich resolution (0.1∘ with 75 vertical levels); the eddy-rich model is designed to be incorporated into the Bluelink operational ocean prediction and reanalysis system. The different resolutions have been developed simultaneously, both to allow for testing at lower resolutions and to permit comparison across resolutions. In this paper, the model is introduced and the individual components are documented. The model performance is evaluated across the three different resolutions, highlighting the relative advantages and disadvantages of running ocean–sea ice models at higher resolution. We find that higher resolution is an advantage in resolving flow through small straits, the structure of western boundary currents, and the abyssal overturning cell but that there is scope for improvements in sub-grid-scale parameterizations at the highest resolution

Novel mutations in the TBX5 gene in patients with Holt-Oram Syndrome

The Holt-Oram syndrome (HOS) is an autosomal dominant condition characterized by upper limb and cardiac malformations. Mutations in the TBX5 gene cause HOS and have also been associated with isolated heart and arm defects. Interactions between the TBX5, GATA4 and NKX2.5 proteins have been reported in humans. We screened the TBX5, GATA4, and NKX2.5 genes for mutations, by direct sequencing, in 32 unrelated patients presenting classical (8) or atypical HOS (1), isolated congenital heart defects (16) or isolated upper-limb malformations (7). Pathogenic mutations in the TBX5 gene were found in four HOS patients, including two new mutations (c.374delG; c.678G > T) in typical patients, and the hotspot mutation c.835C > T in two patients, one of them with an atypical HOS phenotype involving lower-limb malformations. Two new mutations in the GATA4 gene were found in association with isolated upper-limb malformations, but their clinical significance remains to be established. A previously described possibly pathogenic mutation in the NKX2.5 gene (c.73C > 7) was detected in a patient with isolated heart malformations and also in his clinically normal father

“Just one animal among many?” Existential phenomenology, ethics, and stem cell research

Stem cell research and associated or derivative biotechnologies are proceeding at a pace that has left bioethics behind as a discipline that is more or less reactionary to their developments. Further, much of the available ethical deliberation remains determined by the conceptual framework of late modern metaphysics and the correlative ethical theories of utilitarianism and deontology. Lacking, to any meaningful extent, is a sustained engagement with ontological and epistemological critiques, such as with “postmodern” thinking like that of Heidegger’s existential phenomenology. Some basic “Heideggerian” conceptual strategies are reviewed here as a way of remedying this deficiency and adding to ethical deliberation about current stem cell research practices