Dolphin blubber/axial muscle shear : implications for rigid transdermal intramuscular tracking tag trauma in whales

Author Posting. © The Company of Biologists, 2017. This article is posted here by permission of Company of Biologists for personal use, not for redistribution. The definitive version was published in Journal of Experimental Biology 220 (2017): 3717-3723, doi:10.1242/jeb.165282.Whale tracking tags often penetrate semi-rigid blubber, with intramuscular sharp tips and toggling barbs under the subdermal sheath to reduce premature shedding. Tag sites can show persistent regional swellings or depressions. Fibroelastic blubber grips a tag, so if muscle shears relative to blubber during locomotion, the tag tip could cavitate the muscle within overall shearing distance. We modeled shearing of blubber relative to muscle, within the dorsal-ventral peduncular movement range of four common dolphin (Delphinus delphis) cadavers (mean length 186 cm). The net change in angle and hence tip distance moved was calculated with dorsal and ventral flexion, and compared between 1.5 mm diameter needles inserted into blubber only and through blubber into muscle. The greatest shearing value was 3.6 cm, and shearing was most pronounced in the areas ventral and caudal to the dorsal fin. Scaled dummy tags were also inserted and the animal cyclically flexed dorsally and ventrally for 18 h. Tag sites were dissected and cavities around the tag tips documented. If this shearing is comparable in large whales, depressions and regional swellings observed with intramuscular tracking tags are likely the result of tissue loss and repair, respectively. Placing tags para-sagittally anterior to the dorsal fin would cause the least trauma, but pain from such tags remains a concern.This study was undertaken with support from the Office of Naval Research (award no. N00014-13-1-0653 to Cascadia Research Collective).2018-08-1

A synopsis of the Joint Environment and Human Health Programme in the UK

The Joint Environment and Human Health (E&HH) Programme has explored how both man-made and natural changes to the environment can influence human health. Scientists have tackled the complicated mix of environmental, social and economic factors that influence health, particularly focusing on naturally occurring toxins, man-made pollutants, nanoparticles and pathogens to see

Challenges Facing the Sacramento–San Joaquin Delta: Complex, Chaotic, or Simply Cantankerous?

Freshwater is a scarce and precious resource in California; its overall value is being made clear by the current severe drought. The Sacramento–San Joaquin Delta is a critical node in a complex water supply system that extends throughout much of the western U.S. wherein demand is exceeding supply. The Delta also underpins a major component of the U.S. economy, helps feed a substantial part of the country, is a unique and valuable ecological resource, and is a place with a rich cultural heritage. Sustaining the Delta is a problem that manifests itself in many dimensions including the physical structure of the Delta, the conflicting demands for water, changing water quality, rapidly evolving ecological character, and high institutional complexity. The problems of the California Delta are increasingly complex, sometimes chaotic, and always contentious. There is general agreement that current management will sustain neither the Delta ecosystem nor high-quality water exports, as required under the Delta Reform Act, so there is a renewed urgency to address all dimensions of the problem aggressively. Sustainable management of the Delta ecosystem and California’s highly variable water supply, in the face of global climate change, will require bold political decisions that include adjustments to the infrastructure but give equal emphasis to chronic overuse and misuse of water, promote enhanced efficiency of water use, and facilitate new initiatives for ecosystem recovery. This new approach will need to be underpinned by collaborative science that supports ongoing evaluation and re-adjustment of actions. Problems like the Delta are formally “wicked" problems that cannot be “solved” in the traditional sense, but they can be managed with appropriate knowledge and flexible institutions. Where possible, it is advisable to approach major actions incrementally, with an eye toward avoiding catastrophic unexpected outcomes. Collaborative analyses of risks and benefits that consider all dimensions of the problem are essential. Difficult as the problems are, California has the tools and the intellectual resources to manage the Delta problem and achieve the twin goals of a reliable water supply and an ecologically diverse Delta ecosystem

Continuity properties of measurable group cohomology

A version of group cohomology for locally compact groups and Polish modules has previously been developed using a bar resolution restricted to measurable cochains. That theory was shown to enjoy analogs of most of the standard algebraic properties of group cohomology, but various analytic features of those cohomology groups were only partially understood. This paper re-examines some of those issues. At its heart is a simple dimension-shifting argument which enables one to `regularize' measurable cocycles, leading to some simplifications in the description of the cohomology groups. A range of consequences are then derived from this argument. First, we prove that for target modules that are Fr\'echet spaces, the cohomology groups agree with those defined using continuous cocycles, and hence they vanish in positive degrees when the acting group is compact. Using this, we then show that for Fr\'echet, discrete or toral modules the cohomology groups are continuous under forming inverse limits of compact base groups, and also under forming direct limits of discrete target modules. Lastly, these results together enable us to establish various circumstances under which the measurable-cochains cohomology groups coincide with others defined using sheaves on a semi-simplicial space associated to the underlying group, or sheaves on a classifying space for that group. We also prove in some cases that the natural quotient topologies on the measurable-cochains cohomology groups are Hausdorff.Comment: 52 pages. [Nov 22, 2011:] Major re-write with Calvin C. Moore as new co-author. Results from previous version strengthened and several new results added. [Nov 25, 2012:] Final version now available at springerlink.co

Fas Regulates Macrophage Polarization and Fibrogenic Phenotype in a Model of Chronic Ethanol-Induced Hepatocellular Injury

The role of Fas-mediated apoptosis and its effect on proinflammatory cytokine production in early alcoholic liver disease has not been addressed. Wild-type mice (C57Bl/6) or mice with a functional mutation in the Fas ligand (B6

Two-Dimensional Topology of the 2dF Galaxy Redshift Survey

We study the topology of the publicly available data released by the 2dFGRS. The 2dFGRS data contains over 100,000 galaxy redshifts with a magnitude limit of b_J=19.45 and is the largest such survey to date. The data lie over a wide range of right ascension (75 degree strips) but only within a narrow range of declination (10 degree and 15 degree strips). This allows measurements of the two-dimensional genus to be made. The NGP displays a slight meatball shift topology, whereas the SGP displays a bubble like topology. The current SGP data also have a slightly higher genus amplitude. In both cases, a slight excess of overdense regions are found over underdense regions. We assess the significance of these features using mock catalogs drawn from the Virgo Consortium's Hubble Volume LCDM z=0 simulation. We find that differences between the NGP and SGP genus curves are only significant at the 1 sigma level. The average genus curve of the 2dFGRS agrees well with that extracted from the LCDM mock catalogs. We compare the amplitude of the 2dFGRS genus curve to the amplitude of a Gaussian random field with the same power spectrum as the 2dFGRS and find, contradictory to results for the 3D genus of other samples, that the amplitude of the GRF genus curve is slightly lower than that of the 2dFGRS. This could be due to a a feature in the current data set or the 2D genus may not be as sensitive as the 3D genus to non-linear clustering due to the averaging over the thickness of the slice in 2D. (Abridged)Comment: Submitted to ApJ A version with Figure 1 in higher resolution can be obtained from http://www.physics.drexel.edu/~hoyle

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial

Olaparib; Ovarian cancer; TolerabilityOlaparib; Cáncer de ovarios; TolerabilidadOlaparib; Càncer d'ovaris; TolerabilitatObjectives In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1. Methods Eligible patients were randomized to olaparib tablets 300 mg twice daily (N = 260) or placebo (N = 131), with a 2-year treatment cap in most patients. Safety outcomes were analyzed in detail in randomized patients who received at least one dose of study drug (olaparib, n = 260; placebo, n = 130). Results Median time to first onset of the most common hematologic (anemia, neutropenia, thrombocytopenia) and non-hematologic (nausea, fatigue/asthenia, vomiting) adverse events was <3 months in olaparib-treated patients. The first event of anemia, neutropenia, thrombocytopenia, nausea and vomiting lasted a median of <2 months and the first event of fatigue/asthenia lasted a median of 3.48 months in the olaparib group. These adverse events were manageable with supportive treatment and/or olaparib dose modification in most patients, with few patients requiring discontinuation of olaparib. Of 162 patients still receiving olaparib at month 24, 64.2% were receiving the recommended starting dose of olaparib 300 mg twice daily. Conclusions Maintenance olaparib had a predictable and manageable adverse event profile in the newly diagnosed setting with no new safety signals identified. Adverse events usually occurred early, were largely manageable and led to discontinuation in a minority of patients.This work was supported by AstraZeneca and is part of an alliance between AstraZeneca and MSD