In an international trial involving 450 patients with acute subdural hematoma, craniotomy (bone flap replaced) and decompressive craniectomy (bone flap left out) yielded similar disability-related ...outcomes at 12 months.
Aim
The British Isles have been worked for millennia to extract metal ores to feed industrial development, leaving a legacy of mine water pollution that continues to impact freshwater communities in ...many regions. Brown trout (Salmo trutta L.) have long been observed to persist in these metal‐impacted systems as apex predators, with previous studies showing a small number of impacted populations to be highly genetically divergent. We sought to understand the scale of genetic diversity across regions and the repeatability of genetic divergence in trout populations affected by metal pollution.
Location
We examined four mine water‐impacted regions across the British Isles: west Wales, northeast England, southwest England and southeast Ireland.
Methods
We employed a panel of 95 SNP loci to screen 1236 individuals from 71 sites representing paired metal‐impacted and clean sites from across the four regions. From these, we obtained diversity statistics, assessed genetic structuring of populations and modelled historical demographic scenarios to understand which factors most credibly explain genetic variation in divergent populations.
Results
We evidenced hierarchical population structure in the regions studied, in line with expectations from phylogeographic history. However, in a hierarchical analysis of genetic structuring the first level of differentiation was driven by the divergence of the metal‐impacted trout of Cornwall in southwest England. Within regions we observed reduced genetic diversity and repeated patterns of local genetic sub‐structuring between paired samples from metal‐impacted and relatively clean sites. Demographic history analyses suggested the timing of these splits to be relatively recent and to be associated with periods of peak mining activity.
Main conclusions
Our findings demonstrate distinct patterns of genetic isolation and reduced diversity arising from legacy pollution in freshwater ecosystems, with impacts being most apparent where both chemical pollution and physical barriers are present. Management should focus on the amelioration of mine water wash‐out and the removal of barriers to fish movement to safeguard genetic diversity in impacted populations.
Stressors associated with climate change and contaminants, resulting from the activities of humans, are affecting organisms and ecosystems globally. Previous studies suggest that the unique ...characteristics of polar biota, such as slower metabolisms and growth, and the generally stable conditions in their natural environment, cause higher susceptibility to contamination and climate change than those in temperate and tropical areas. We investigated the effects of increased temperature and decreased salinity on copper toxicity in four subantarctic marine invertebrates using realistic projected conditions under a future climatic change scenario for this region. We hypothesised that these relatively subtle shifts in environmental stressors would impact the sensitivity of cold-adapted species to copper. The four test species were: a copepod Harpacticus sp.; isopod Limnoria stephenseni; flatworm Obrimoposthia ohlini; and bivalve Gaimardia trapesina. These species occupy a range of ecological niches, spanning intertidal and subtidal nearshore zones. We predicted that species would differ in their tolerance to stressors, depending on where they occurred within this ecological gradient. Organisms were exposed to the multiple stressors in a factorial design in laboratory based toxicity tests. Sensitivity estimates for copper (LC50) were calculated using a novel statistical approach which directly assessed the impacts of the multiple stressors. In three of the four species tested, sensitivity to copper was amplified by small increases in temperature (2-4 °C). The effects of salinity were more variable but a decrease of as little as 2 ppt caused a significant effect in one species. This study provides some of the first evidence that high latitude species may be at increased risk from contaminants under projected future climate conditions. This interaction, between contaminants and the abiotic environment, highlights a potential pathway to biodiversity loss under a changing climate.
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•Climate change affected copper toxicity to all four marine invertebrates tested.•The effects on toxicity differed with each of the four species tested.•The copepod was the most sensitive to both copper and climate change stressors.•Subantarctic species may be more susceptible than temperate counterparts.
These subantarctic marine invertebrate species, particularly the copepod Harpacticus sp, are acutely susceptible to changes in temperature and salinity in the presence of a contaminant.
Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to ...stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal, and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally responsive systemic cancers with meningioma subgroups, reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histologic grading. Superenhancer signatures predicted drug dependencies with superior
efficacy to treatment based upon the
genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth
. Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies. SIGNIFICANCE: Enhancer landscapes inform prognostic classification of aggressive meningiomas, identifying tumors at high risk of recurrence, and reveal previously unknown therapeutic targets. Druggable dependencies discovered through epigenetic profiling potentially guide treatment of intractable meningiomas.
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The rivers of southern England and northern France which drain into the English Channel contain several genetically unique groups of trout (Salmo trutta L.) that have suffered dramatic declines in ...numbers over the past 40 years. Knowledge of levels and patterns of genetic diversity is essential for effective management of these vulnerable populations. Using restriction site‐associated DNA sequencing (RADseq) data, we describe the development and characterisation of a panel of 95 single nucleotide polymorphism (SNP) loci for trout from this region and investigate their applicability and variability in both target (i.e., southern English) and non‐target trout populations from northern Britain and Ireland. In addition, we present three case studies which demonstrate the utility and resolution of these genetic markers at three levels of spatial separation:(a) between closely related populations in nearby rivers, (b) within a catchment and (c) when determining parentage and familial relationships between fish sampled from a single site, using both empirical and simulated data. The SNP loci will be useful for population genetic and assignment studies on brown trout within the UK and beyond.
The accreting millisecond X-ray pulsar SAX J1808.4−3658 shows a peculiar orbital evolution that proceeds at a very fast pace. It is important to identify the underlying mechanism responsible for this ...behavior because it can help to understand how this system evolves and which physical processes (such as mass loss or spin-orbit coupling) are occurring in the binary. It has also been suggested that, when in quiescence, SAX J1808.4−3658 turns on as a radio pulsar, a circumstance that might provide a link between accreting millisecond pulsars and black-widow (BW) radio pulsars. In this work, we report the results of a deep radio pulsation search at 2 GHz using the Green Bank Telescope in 2014 August and an X-ray study of the 2015 outburst with Chandra, Swift XRT, and INTEGRAL. In quiescence, we detect no radio pulsations and place the strongest limit to date on the pulsed radio flux density of any accreting millisecond pulsar. We also find that the orbit of SAX J1808.4−3658 continues evolving at a fast pace. We compare the orbital evolution of SAX J1808.4−3658 to that of several other accreting and nonaccreting binaries, including BWs, redbacks, cataclysmic variables, black holes, and neutron stars in low-mass X-ray binaries. We discuss two possible scenarios: either the neutron star has a large moment of inertia and is ablating the donor, generating mass loss with an efficiency of 40%, or the donor star has a strong magnetic field of at least 1 kG and is undergoing quasi-cyclic variations due to spin-orbit coupling.
Proopiomelanocortin (POMC) neurons contribute to the regulation of many physiological processes; the majority of which have been attributed to the release of peptides produced from the POMC ...prohormone such as α-MSH, which plays key roles in food intake and metabolism. However, it is now clear that POMC neurons also release amino acid transmitters that likely contribute to the overall function of POMC cells. Recent work indicates that constitutive deletion of these transmitters can affect metabolic phenotypes, but also that the expression of GABAergic or glutamatergic markers changes throughout development. The goal of the present study was to determine whether the release of glutamate or GABA from POMC neurons in the adult mouse contributes notably to energy balance regulation. Disturbed release of glutamate or GABA specifically from POMC neurons in adult mice was achieved using a tamoxifen-inducible
construct (
expressed in mice also carrying floxed versions of
or
and
, encoding the vesicular glutamate transporter type 2 and GAD67 and GAD65 proteins, respectively. All mice in the experiments received tamoxifen injections, but control mice lacked the tamoxifen-inducible Cre sequence. Body weight was unchanged in
and
- or
-deleted female and male mice. Additionally, no significant differences in glucose tolerance or refeeding after an overnight fast were observed. These data collectively suggest that the release of GABA or glutamate from POMC neurons in adult mice does not significantly contribute to the metabolic parameters tested here. In light of prior work, the data also suggest that amino acid transmitter release from POMC cells may contribute to separate functions in the adult versus the developing mouse.
To investigate the association between optical coherence tomography (OCT) parameters and long-term visual recovery following optic chiasm decompression surgery.
Prospective cohort study.
Consecutive ...patients who underwent pituitary or parasellar tumor resection between January 2009 to December 2018 were recruited in a single-center, 2-year prospective, longitudinal cohort study. Best-corrected visual acuity, visual fields, and OCT retinal nerve fiber layer (RNFL) thickness, macular thickness and volume were assessed preoperatively, and at 6 weeks, 6 months, and 2 years postoperatively. Long-term visual field recovery and maintenance were defined as a mean deviation of >−3 at 24 months, and visual acuity recovery and maintenance were defined as a logarithm of minimal angle of resolution (logMAR) of 0 (Snellen 20/20) or better at 24 months.
A total of 239 patients (129 men, 110 women; mean ± SD age: 52 ± 16 years) were included. Multiple logistic regression analysis demonstrated that increased inferior RNFL thickness (per 10 μm) was associated with higher odds of long-term visual field recovery and maintenance (odds ratio OR: 1.26; 95% confidence interval CI: 1.12-1.41; Q < 0.001), and greater superior RNFL thickness (per 10 μm) was associated with higher odds of visual acuity recovery and maintenance (OR: 1.13; 95% CI: 1.03-1.27; Q = 0.031). A multivariable risk prediction model developed for long-term visual field recovery and maintenance that incorporated age, preoperative visual function, and RNFL thickness demonstrated C-statistics of 0.83 (95% CI: 0.72-0.94).
Preoperative RNFL thickness was associated with long-term visual recovery and maintenance following chiasmal decompression. The multivariable risk prediction model developed in the present study may assist with preoperative patient counseling and prognosis.
Anesthetic agents are known greenhouse gases with hundreds to thousands of times the global warming impact compared with carbon dioxide. We sought to mitigate the negative environmental and financial ...impacts of our practice in the perioperative setting through multidisciplinary staff engagement and provider education on flow rate reduction and volatile agent choice. These efforts led to a 64% per case reduction in carbon dioxide equivalent emissions (163 kg in Fiscal Year 2012, compared with 58 kg in Fiscal Year 2015), as well as a cost savings estimate of $25,000 per month.
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