Lepidorbitoides (Foraminifera) from the lower Maastrichtian Kallankuruchchi Formation, Cauvery Basin, India: Morphometry and paleobiogeography

The southernmost occurrence of the early Maastrichtian larger benthic foraminifera (LBF) in Tethys is known from the Kallankuruchchi Formation in the Cauvery Basin, SE India, represented by Lepidorbitoides-Siderolites assemblages. The systematics, age and paleobiogeography of Lepidorbitoides here have as yet remained unresolved due to lack of information particularly on the nepionic arrangement, whereas their links with the Western Tethyan and Caribbean biogeographic domains were speculated. Lepidorbitoides, studied from the same level in seven samples in two separate areas, invariably possess quadriserial nepionts and adauxiliary chamberlets, whose mean number ranges from 3.79 to 4.67. The ratio between the sample means of the internal diameter of deuteroconch and protoconch varies between 1.72 and 1.86. The equatorial layer in the early stage consists of arcuate chambers with basal stolons, and ogival-to spatulate chamberlets with annular and oblique stolons in the later stages. These features are consistent with the phylogenetically advanced members of the Western Tethyan Lepidorbitoides lineage, such as L. minor (Schlumberger) and L. socialis (Leymerie), and all samples were assigned to the transitional development stages of these species based on the morphometry. The taxonomic status of some Lepidorbitoides species, originally described from the Kallankuruchchi Formation and widely adopted in previous works, such as L. blanfordi (Rao) and L. inornata (Rao), are not justified. We extend the geographic range of Western Tethyan Lepidorbitoides to southern India. © 2017 Elsevier Lt

Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial.

Background Hyperbaric oxygen has been used as a therapy for patients experiencing chronic intestinal syndromes after pelvic radiotherapy for decades, yet the evidence to support the use of this therapy is based almost exclusively on non-randomised studies. We aimed to provide conclusive results for the clinical benefits of hyperbaric oxygen in patients with chronic bowel dysfunction after radiotherapy for pelvic malignancies.Methods HOT2 was a double-blind, sham-controlled, phase 3 randomised study of patients (≥18 years) with chronic gastrointestinal symptoms for 12 months or more after radiotherapy and which persisted despite at least 3 months of optimal medical therapy and no evidence of cancer recurrence. Participants were stratified by participating hyperbaric centre and randomly assigned (2:1) by a computer-generated list (block size nine or 12) to receive treatment with hyperbaric oxygen therapy or sham. Participants in the active treatment group breathed 100% oxygen at 2·4 atmospheres of absolute pressure (ATA) and the control group breathed 21% oxygen at 1·3 ATA; both treatment groups received 90-min air pressure exposures once daily for 5 days per week for a total of 8 weeks (total of 40 exposures). Staff at the participating hyperbaric medicine facilities knew the allocated treatment, but patients, clinicians, nurse practitioners, and other health-care professionals associated with patients' care were masked to treatment allocation. Primary endpoints were changes in the bowel component of the modified Inflammatory Bowel Disease Questionnaire (IBDQ) score and the IBDQ rectal bleeding score 12 months after start of treatment relative to baseline. The primary outcome was analysed in a modified intention-to-treat population, excluding patients who did not provide IBDQ scores within a predetermined time-frame. All patients have completed 12 months of follow-up and the final analysis is complete. The trial is registered with the ISRCTN registry, number ISRCTN86894066.Findings Between Aug 14, 2009, and Oct 23, 2012, 84 participants were randomly assigned: 55 to hyperbaric oxygen and 29 to sham control. 75 (89%) participants received 40 pressure exposures, all participants returned the IBDQ at baseline, 75 (89%) participants returned the IBDQ at 2 weeks post-treatment, and 79 (94%) participants returned the IBDQ at 12 months post-start of treatment. Patients were excluded from analyses of co-primary endpoints if they had missing IBDQ scores for intestinal function or rectal bleeding at baseline or at 12 months. In an analysis of 46 participants in the active treatment group and 23 participants in the control group, we found no significant differences in the change of IBDQ bowel component score (median change from baseline to 12 months of 4 (IQR -3 to 11) in the treatment group vs 4 (-6 to 9) in the sham group; Mann-Whitney U score 0·67, p=0·50). In an analysis of 29 participants in the active treatment group and 11 participants in the sham group with rectal bleeding at baseline, we also found no significant differences in the change of IBDQ rectal bleeding score (median change from baseline to 12 months of 3 [1 to 3] in the treatment group vs 1 [1 to 2] in the sham group; U score 1·69, p=0·092). Common adverse events in both groups were eye refractive changes (three [11%] of 28 patients in the control group vs 16 [30%] of 53 patients in the treatment group), increased fatigue (three [11%] vs two [4%]), and ear pain (six [21%] vs 15 [28%]). Eight serious adverse events were reported in eight patients: two were reported in two patients in the control group (tonsillitis requiring surgery [grade 3]; recurrent cancer of the vulva [grade 4]) and six serious adverse events were reported in six patients in the treatment group (malignant spinal cord compression requiring surgery [grade 3]; malignant paraortic lymph node involvement requiring surgery [grade 3]; recurrence of vomiting and dehydration [grade 3]; diarrhoea and fever associated with Campylobacter infection [grade 3]; recurrence of abdominal pain, bloating, diarrhoea, and urinary tract infection [grade 3]; aneurysm [grade 4]), none of which were deemed treatment-related.Interpretation We found no evidence that patients with radiation-induced chronic gastrointestinal symptoms, including those patients with rectal bleeding, benefit from hyperbaric oxygen therapy. These findings contrast with evidence used to justify current practices, and more level 1 evidence is urgently needed.Funding Cancer Research UK and National Health Service (NHS) funding to the National Institute of Health Research Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research

Bottom mixed layer oxygen dynamics in the Celtic Sea

The seasonally stratified continental shelf seas are highly productive, economically important environments which are under considerable pressure from human activity. Global dissolved oxygen concentrations have shown rapid reductions in response to anthropogenic forcing since at least the middle of the twentieth century. Oxygen consumption is at the same time linked to the cycling of atmospheric carbon, with oxygen being a proxy for carbon remineralisation and the release of CO2. In the seasonally stratified seas the bottom mixed layer (BML) is partially isolated from the atmosphere and is thus controlled by interplay between oxygen consumption processes, vertical and horizontal advection. Oxygen consumption rates can be both spatially and temporally dynamic, but these dynamics are often missed with incubation based techniques. Here we adopt a Bayesian approach to determining total BML oxygen consumption rates from a high resolution oxygen time-series. This incorporates both our knowledge and our uncertainty of the various processes which control the oxygen inventory. Total BML rates integrate both processes in the water column and at the sediment interface. These observations span the stratified period of the Celtic Sea and across both sandy and muddy sediment types. We show how horizontal advection, tidal forcing and vertical mixing together control the bottom mixed layer oxygen concentrations at various times over the stratified period. Our muddy-sand site shows cyclic spring-neap mediated changes in oxygen consumption driven by the frequent resuspension or ventilation of the seabed. We see evidence for prolonged periods of increased vertical mixing which provide the ventilation necessary to support the high rates of consumption observed

Assessment of the methodology for establishing the EU list of critical raw materials : background report

This report presents the results of work carried out by the Directorate General (DG) Joint Research Centre (JRC) of the European Commission (EC), in close cooperation with Directorate-General for Internal Market, Industry, Entrepreneurship and SMEs (GROW), in the context of the revision of the EC methodology that was used to identify the list of critical raw materials (CRMs) for the EU in 2011 and 2014 (EC 2011, 2014). As a background report, it complements the corresponding Guidelines Document, which contains the "ready-to-apply" methodology for updating the list of CRMs in 2017. This background report highlights the needs for updating the EC criticality methodology, the analysis and the proposals for improvement with related examples, discussion and justifications. However, a few initial remarks are necessary to clarify the context, the objectives of the revision and the approach. As the in-house scientific service of the EC, DG JRC was asked to provide scientific advice to DG GROW in order to assess the current methodology, identify aspects that have to be adapted to better address the needs and expectations of the list of CRMs and ultimately propose an improved and integrated methodology. This work was conducted closely in consultation with the adhoc working group on CRMs, who participated in regular discussions and provided informed expert feedback. The analysis and subsequent revision started from the assumption that the methodology used for the 2011 and 2014 CRMs lists proved to be reliable and robust and, therefore, the JRC mandate was focused on fine-tuning and/or targeted incremental methodological improvements. An in depth re-discussion of fundamentals of criticality assessment and/or major changes to the EC methodology were not within the scope of this work. High priority was given to ensure good comparability with the criticality exercises of 2011 and 2014. The existing methodology was therefore retained, except for specific aspects for which there were policy and/or stakeholder needs on the one hand, or strong scientific reasons for refinement of the methodology on the other. This was partially facilitated through intensive dialogue with DG GROW, the CRM adhoc working group, other key EU and extra-EU stakeholders

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Work-related pesticide poisoning among farmers in two villages of Southern China: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Pesticide poisoning is an important health problem among Chinese farm workers, but there is a paucity of pesticide poisoning data from China. Using the WHO standard case definition of a possible acute pesticide poisoning, we investigated the prevalence and risk factors of acute work-related pesticide poisoning among farmers in Southern China.</p> <p>Methods</p> <p>A stratified sample of 910 pesticide applicators from two villages in southern China participated in face-to-face interviews. Respondents who self-reported having two or more of a list of sixty-six symptoms within 24 hours after pesticide application were categorized as having suffered acute pesticide poisoning. The association between the composite behavioral risk score and pesticide poisoning were assessed in a multivariate logistic model.</p> <p>Results</p> <p>A total of 80 (8.8%) pesticide applicators reported an acute work-related pesticide poisoning. The most frequent symptoms among applicators were dermal (11.6%) and nervous system (10.7%) symptoms. Poisoning was more common among women, farmers in poor areas, and applicators without safety training (all p < 0.001). After controlling for gender, age, education, geographic area and the behavioral risk score, farmers without safety training had an adjusted odds ratio of 3.22 (95% CI: 1.86-5.60). The likelihood of acute pesticide poisoning was also significantly associated with number of exposure risk behaviors. A significant "dose-response" relationship between composite behavioral risk scores calculated from 9 pesticides exposure risk behaviors and the log odds of pesticide poisoning prevalence was seen among these Chinese farmers (R²= 0.9246).</p> <p>Conclusions</p> <p>This study found that 8.8% of Chinese pesticide applicators suffered acute pesticide poisoning and suggests that pesticide safety training, safe application methods, and precautionary behavioral measures could be effective in reducing the risk of pesticide poisoning.</p

Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation. Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.Peer reviewe

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases

Caspase involvement in autophagy

Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development