Conservation implications and opportunities of mining activities for terrestrial mammal habitat

Mining companies increasingly commit to a net positive impact on biodiversity. However, assessing the industry's progress toward achieving this goal is limited by knowledge of current mining threats to biodiversity and the relevant opportunities available for them to improve conservation outcomes. Here, we investigate the global exposure of terrestrial mammal habitat to mining activities, revealing the 136 species with > 30% of their habitat within 10 km of a mining property or exploration site. One third (n = 42) of these species are already threatened with extinction according to the International Union for Conservation of Nature (IUCN), suggesting projected increased demand for minerals may push some species beyond critical thresholds. Moreover, 28% (n = 33) of species are Data Deficient, illustrating tangible ways for industry to fill current knowledge gaps. However, large discrepancies between our results and the species currently listed as threatened by mining in the IUCN Red List, suggest other species may be at risk and that conservation tools and analyses based on these data may underestimate the benefits of averting such threats. We recommend ways to better capture mining threats to species within IUCN Red List assessments and discuss how these changes could improve conservation outcomes in mineral-rich areas

Shaping of nova remnants by binary motion

We present the results of 2.5D hydrodynamic calculations of the effects of the underlying binary system on shaping the ejecta in a classical nova outburst. In the model, the outburst takes place in the form of a wind with secularly increasing velocity. This wind flows past a binary companion, which experiences a frictional drag force and transfers energy and angular momentum from its orbit into the expanding envelope. We find that many of the features seen in classical novaremnants can be reproduced, including polar blobs, polar rings and shells with tropical and equatorial bands. The features seen in the shells correlate with speed class in the observed manner — fast novae produce spherical shells, whereas slower novae produce banded shells and polar blobs. The effects of radiative cooling andthe Rayleigh-Taylor instability on the shells are discussed. It is found that, as observations appear to indicate, the shells of fast novae should comprise a few, large clumps, whereas the shells of slower novae will be clumped on scales which are small compared to the shell radius

Bipolar recurrent nova outbursts – I. Hydrodynamic models

We describe hydrodynamic models of bipolar outbursts in recurrent nova systems containing a red giant with a dense wind. Two mechanisms are investigated for the production of the bipolarity observed in the outbursts of some such systems - a model in which the outburst occurs as a point explosion in an anisotropic wind, and one in which the wind is isotropic but the outburst itself is intrinsically bipolar. It is argued on the basis of radio observations of RS Oph (1985) that the latter model is more likely to be appropriate. The numerical computations of bipolar explosions also show that the ejection of parcels of gas at highly supersonic, and oppositely directed, velocities into a dense surrounding medium gives rise to bowshocks which interact in such a way as to give a dense ring of material in a plane normal to the line of ejection

Astrophysical Fluids of Novae: High Resolution Pre-decay X-ray spectrum of V4743 Sagittarii

Eight X-ray observations of V4743 Sgr (2002), observed with Chandra and XMM-Newton are presented. The nova turned off some time between days 301.9 and 371, and the X-ray flux subsequently decreased from day 301.9 to 526 following an exponential decline time scale of $(96 \pm 3)$ days. We use the absorption lines present in the SSS spectrum for diagnostic purposes, and characterize the physics and the dynamics of the expanding atmosphere during the explosion of the nova. The information extracted from this first stage is then used as input for computing full photoionization models of the ejecta in V4743 Sgr. The SSS spectrum is modeled with a simple black-body and multiplicative Gaussian lines, which provides us of a general kinematical picture of the system, before it decays to its faint phase (Ness et al. 2003). In the grating spectra taken between days 180.4 and 370, we can resolve the line profiles of absorption lines arising from H-like and He-like C, N, and O, including transitions involving higher principal quantum numbers. Except for a few interstellar lines, all lines are significantly blue-shifted, yielding velocities between 1000 and 6000 km/s which implies an ongoing mass loss. It is shown that significant expansion and mass loss occur during this phase of the explosion, at a rate $\dot{M} \approx (3-5) \times 10^{-4} ~ (\frac{L}{L_{38}}) ~ M_{\odot}/yr$. Our measurements show that the efficiency of the amount of energy used for the motion of the ejecta, defined as the ratio between the kinetic luminosity $L_{\rm kin}$ and the radiated luminosity $L_{\rm rad}$, is of the order of one.Comment: 25 pages, 9 figures. Accepted in book: Recent Advances in Fluid Dynamics with Environmental Applications, pp.365-39

Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma.

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1-2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders

The epidemiology of injuries across the weight-training sports

Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma

Neoadjuvant therapy followed by surgery is the standard of care for locally advanced esophageal adenocarcinoma (EAC). Unfortunately, response to neoadjuvant chemotherapy (NAC) is poor (20-37%), as is the overall survival benefit at five years (9%). The EAC genome is complex and heterogeneous between patients, and it is not yet understood whether specific mutational patterns may result in chemotherapy sensitivity or resistance. To identify associations between genomic events and response to NAC in EAC, a comparative genomic analysis was performed in 65 patients with extensive clinical and pathological annotation using whole-genome sequencing (WGS). We defined response using Mandard Tumor Regression Grade (TRG), with responders classified as TRG1-2 (n = 27) and non-responders classified as TRG4-5 (n =38). We report a higher non-synonymous mutation burden in responders (median 2.08/Mb vs. 1.70/Mb, p = 0.036) and elevated copy number variation in non-responders (282 vs. 136/patient, p < 0.001). We identified copy number variants unique to each group in our cohort, with cell cycle (CDKN2A, CCND1), c-Myc (MYC), RTK/PIK3 (KRAS, EGFR) and gastrointestinal differentiation (GATA6) pathway genes being specifically altered in non-responders. Of note, NAV3 mutations were exclusively present in the non-responder group with a frequency of 22%. Thus, lower mutation burden, higher chromosomal instability and specific copy number alterations are associated with resistance to NAC

Antigen-Specific T-Cell Activation Distinguishes between Recent and Remote Tuberculosis Infection

Rationale: Current diagnostic tests fail to identify individuals at higher risk of progression to tuberculosis disease, such as those with recent Mycobacterium tuberculosis infection, who should be prioritized for targeted preventive treatment. Objectives: To define a blood-based biomarker, measured with a simple flow cytometry assay, that can stratify different stages of tuberculosis infection to infer risk of disease. Methods: South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion 1 yr) infection. We defined the ΔHLA-DR median fluorescence intensity biomarker as the difference in HLA-DR expression between IFN-γ+ TNF+ Mycobacterium tuberculosis-specific T cells and total CD3+ T cells. Biomarker performance was assessed by blinded prediction in untouched test cohorts with recent versus persistent infection or tuberculosis disease and by unblinded analysis of asymptomatic adolescents with tuberculosis infection who remained healthy (nonprogressors) or who progressed to microbiologically confirmed disease (progressors). Measurements and Main Results: In the test cohorts, frequencies of Mycobacterium tuberculosis-specific T cells differentiated between QuantiFERON-TB- (n = 25) and QuantiFERON-TB+ (n = 47) individuals (area under the receiver operating characteristic curve, 0.94; 95% confidence interval, 0.87-1.00). ΔHLA-DR significantly discriminated between recent (n = 20) and persistent (n = 22) QuantiFERON-TB+ (0.91; 0.83-1.00); persistent QuantiFERON-TB+ and newly diagnosed tuberculosis (n = 19; 0.99; 0.96-1.00); and tuberculosis progressors (n = 22) and nonprogressors (n = 34; 0.75; 0.63-0.87). However, ΔHLA-DR median fluorescent intensity could not discriminate between recent QuantiFERON-TB+ and tuberculosis (0.67; 0.50-0.84). Conclusions: The ΔHLA-DR biomarker can identify individuals with recent QuantiFERON-TB conversion and those with disease progression, allowing targeted provision of preventive treatment to those at highest risk of tuberculosis. Further validation studies of this novel immune biomarker in various settings and populations at risk are warranted