Large sulfur isotope fractionations in Martian sediments at Gale crater

Variability in the sulfur isotopic composition in sediments can reflect atmospheric, geologic and biological processes. Evidence for ancient fluvio-lacustrine environments at Gale crater on Mars and a lack of efficient crustal recycling mechanisms on the planet suggests a surface environment that was once warm enough to allow the presence of liquid water, at least for discrete periods of time, and implies a greenhouse effect that may have been influenced by sulfur-bearing volcanic gases. Here we report in situ analyses of the sulfur isotopic compositions of SO2 volatilized from ten sediment samples acquired by NASA’s Curiosity rover along a 13 km traverse of Gale crater. We find large variations in sulfur isotopic composition that exceed those measured for Martian meteorites and show both depletion and enrichment in 34S. Measured values of δ34S range from −47 ± 14‰ to 28 ± 7‰, similar to the range typical of terrestrial environments. Although limited geochronological constraints on the stratigraphy traversed by Curiosity are available, we propose that the observed sulfur isotopic signatures at Gale crater can be explained by equilibrium fractionation between sulfate and sulfide in an impact-driven hydrothermal system and atmospheric processing of sulfur-bearing gases during transient warm periods

Ancient DNA Elucidates the Controversy about the Flightless Island Hens (Gallinula sp.) of Tristan da Cunha

A persistent controversy surrounds the flightless island hen of Tristan da Cunha, Gallinula nesiotis. Some believe that it became extinct by the end of the 19th century. Others suppose that it still inhabits Tristan. There is no consensus about Gallinula comeri, the name introduced for the flightless moorhen from the nearby island of Gough. On the basis of DNA sequencing of both recently collected and historical material, we conclude that G. nesiotis and G. comeri are different taxa, that G. nesiotis indeed became extinct, and that G. comeri now inhabits both islands. This study confirms that among gallinules seemingly radical adaptations (such as the loss of flight) can readily evolve in parallel on different islands, while conspicuous changes in other morphological characters fail to occur

A Model of a MAPK•Substrate Complex in an Active Conformation: A Computational and Experimental Approach

The mechanisms by which MAP kinases recognize and phosphorylate substrates are not completely understood. Efforts to understand the mechanisms have been compromised by the lack of MAPK-substrate structures. While MAPK-substrate docking is well established as a viable mechanism for bringing MAPKs and substrates into close proximity the molecular details of how such docking promotes phosphorylation is an unresolved issue. In the present study computer modeling approaches, with restraints derived from experimentally known interactions, were used to predict how the N-terminus of Ets-1 associates with ERK2. Interestingly, the N-terminus does not contain a consensus-docking site ((R/K)2-3-X2-6-ΦA-X-ΦB, where Φ is aliphatic hydrophobic) for ERK2. The modeling predicts that the N-terminus of Ets-1 makes important contributions to the stabilization of the complex, but remains largely disordered. The computer-generated model was used to guide mutagenesis experiments, which support the notion that Leu-11 and possibly Ile-13 and Ile-14 of Ets-1 1-138 (Ets) make contributions through binding to the hydrophobic groove of the ERK2 D-recruiting site (DRS). Based on the modeling, a consensus-docking site was introduced through the introduction of an arginine at residue 7, to give the consensus 7RK-X2-ΦA-X-ΦB13. This results in a 2-fold increase in kcat/Km for the phosphorylation of Ets by ERK2. Similarly, the substitution of the N-terminus for two different consensus docking sites derived from Elk-1 and MKK1 also improves kcat/Km by two-fold compared to Ets. Disruption of the N-terminal docking through deletion of residues 1-23 of Ets results in a 14-fold decrease in kcat/Km, with little apparent change in kcat. A peptide that binds to the DRS of ERK2 affects Km, but not kcat. Our kinetic analysis suggests that the unstructured N-terminus provides 10-fold uniform stabilization of the ground state ERK2•Ets•MgATP complex and intermediates of the enzymatic reaction

Mothers' AdvocateS In the Community (MOSAIC)- non-professional mentor support to reduce intimate partner violence and depression in mothers: a cluster randomised trial in primary care

Background : Effective interventions to increase safety and wellbeing of mothers experiencing intimate partner violence (IPV) are scarce. As much attention is focussed on professional intervention, this study aimed to determine the effectiveness of non-professional mentor support in reducing IPV and depression among pregnant and recent mothers experiencing, or at risk of IPV.Methods : MOSAIC was a cluster randomised trial in 106 primary care (maternal and child health nurse and general practitioner) clinics in Melbourne, Australia. 63/106 clinics referred 215 eligible culturally and linguistically diverse women between January 2006 and December 2007. 167 in the intervention (I) arm, and 91 in the comparison (C) arm. 174 (80.9%) were recruited. 133 (76.4%) women (90 I and 43 C) completed follow-up at 12 months.Intervention: 12 months of weekly home visiting from trained and supervised local mothers, (English &amp; Vietnamese speaking) offering non-professional befriending, advocacy, parenting support and referrals.Main outcome measures: Primary outcomes; IPV (Composite Abuse Scale CAS) and depression (Edinburgh Postnatal Depression Scale EPDS); secondary measures included wellbeing (SF-36), parenting stress (PSI-SF) and social support (MOS-SF) at baseline and follow-up.Analysis: Intention-to-treat using multivariable logistic regression and propensity scoring.Results : There was evidence of a true difference in mean abuse scores at follow-up in the intervention compared with the comparison arm (15.9 vs 21.8, AdjDiff -8.67, CI -16.2 to -1.15). There was weak evidence for other outcomes, but a trend was evident favouring the intervention: proportions of women with CAS scores &ge;7, 51/88 (58.4%) vs 27/42 (64.3%) AdjOR 0.47, CI 0.21 to 1.05); depression (EPDS score &ge;13) (19/85, 22% (I) vs 14/43, 33% (C); AdjOR 0.42, CI 0.17 to 1.06); physical wellbeing mean scores (PCS-SF36: AdjDiff 2.79; CI -0.40 to 5.99); mental wellbeing mean scores (MCS-SF36: AdjDiff 2.26; CI -1.48 to 6.00). There was no observed effect on parenting stress. 82% of women mentored would recommend mentors to friends in similar situations.Conclusion : Non-professional mentor mother support appears promising for improving safety and enhancing physical and mental wellbeing among mothers experiencing intimate partner violence referred from primary care.<br /

CONSORT 2010 statement: extension to randomised pilot and feasibility trials [on behalf of the PAFS consensus group*]

The Consolidated Standards of Reporting Trials (CONSORT) statement is a guideline designed to improve the transparency and quality of the reporting of randomised controlled trials (RCTs). In this article we present an extension to that statement for randomised pilot and feasibility trials conducted in advance of a future definitive RCT. The checklist applies to any randomised study in which a future definitive RCT, or part of it, is conducted on a smaller scale, regardless of its design (eg, cluster, factorial, crossover) or the terms used by authors to describe the study (eg, pilot, feasibility, trial, study). The extension does not directly apply to internal pilot studies built into the design of a main trial, non-randomised pilot and feasibility studies, or phase II studies, but these studies all have some similarities to randomised pilot and feasibility studies and so many of the principles might also apply. The development of the extension was motivated by the growing number of studies described as feasibility or pilot studies and by research that has identified weaknesses in their reporting and conduct. We followed recommended good practice to develop the extension, including carrying out a Delphi survey, holding a consensus meeting and research team meetings, and piloting the checklist. The aims and objectives of pilot and feasibility randomised studies differ from those of other randomised trials. Consequently, although much of the information to be reported in these trials is similar to those in randomised controlled trials (RCTs) assessing effectiveness and efficacy, there are some key differences in the type of information and in the appropriate interpretation of standard CONSORT reporting items. We have retained some of the original CONSORT statement items, but most have been adapted, some removed, and new items added. The new items cover how participants were identified and consent obtained; if applicable, the prespecified criteria used to judge whether or how to proceed with a future definitive RCT; if relevant, other important unintended consequences; implications for progression from pilot to future definitive RCT, including any proposed amendments; and ethical approval or approval by a research review committee confirmed with a reference number. This article includes the 26 item checklist, a separate checklist for the abstract, a template for a CONSORT flowchart for these studies, and an explanation of the changes made and supporting examples. We believe that routine use of this proposed extension to the CONSORT statement will result in improvements in the reporting of pilot trials. Editor’s note: In order to encourage its wide dissemination this article is freely accessible on the BMJ and Pilot and Feasibility Studies journal websites

A critical review of the research literature on Six Sigma, Lean and StuderGroup's Hardwiring Excellence in the United States: the need to demonstrate and communicate the effectiveness of transformation strategies in healthcare

<p>Abstract</p> <p>Background</p> <p>U.S. healthcare organizations are confronted with numerous and varied transformational strategies promising improvements along all dimensions of quality and performance. This article examines the peer-reviewed literature from the U.S. for evidence of effectiveness among three current popular transformational strategies: Six Sigma, Lean/Toyota Production System, and Studer's Hardwiring Excellence.</p> <p>Methods</p> <p>The English language health, healthcare management, and organizational science literature (up to December 2007) indexed in Medline, Web of Science, ABI/Inform, Cochrane Library, CINAHL, and ERIC was reviewed for studies on the aforementioned transformation strategies in healthcare settings. Articles were included if they: appeared in a peer-reviewed journal; described a specific intervention; were not classified as a pilot study; provided quantitative data; and were not review articles. Nine references on Six Sigma, nine on Lean/Toyota Production System, and one on StuderGroup meet the study's eligibility criteria.</p> <p>Results</p> <p>The reviewed studies universally concluded the implementations of these transformation strategies were successful in improving a variety of healthcare related processes and outcomes. Additionally, the existing literature reflects a wide application of these transformation strategies in terms of both settings and problems. However, despite these positive features, the vast majority had methodological limitations that might undermine the validity of the results. Common features included: weak study designs, inappropriate analyses, and failures to rule out alternative hypotheses. Furthermore, frequently absent was any attention to changes in organizational culture or substantial evidence of lasting effects from these efforts.</p> <p>Conclusion</p> <p>Despite the current popularity of these strategies, few studies meet the inclusion criteria for this review. Furthermore, each could have been improved substantially in order to ensure the validity of the conclusions, demonstrate sustainability, investigate changes in organizational culture, or even how one strategy interfaced with other concurrent and subsequent transformation efforts. While informative results can be gleaned from less rigorous studies, improved design and analysis can more effectively guide healthcare leaders who are motivated to transform their organizations and convince others of the need to employ such strategies. Demanding more exacting evaluation of projects consultants, or partnerships with health management researchers in academic settings, can support such efforts.</p

Effectiveness and cost-effectiveness of a group-based pain self-management intervention for patients undergoing total hip replacement: Feasibility study for a randomized controlled trial

Background: Total hip replacement (THR) is a common elective surgical procedure and can be effective for reducing chronic pain. However, waiting times can be considerable. A pain self-management intervention may provide patients with skills to more effectively manage their pain and its impact during their wait for surgery. This study aimed to evaluate the feasibility of conducting a randomized controlled trial to assess the effectiveness and cost-effectiveness of a group-based pain self-management course for patients undergoing THR.Methods: Patients listed for a THR at one orthopedic center were posted a study invitation pack. Participants were randomized to attend a pain self-management course plus standard care or standard care only. The lay-led course was delivered by Arthritis Care and consisted of two half-day sessions prior to surgery and one full-day session after surgery. Participants provided outcome and resource-use data using a diary and postal questionnaires prior to surgery and one month, three months and six months after surgery. Brief telephone interviews were conducted with non-participants to explore barriers to participation.Results: Invitations were sent to 385 eligible patients and 88 patients (23%) consented to participate. Interviews with 57 non-participants revealed the most common reasons for non-participation were views about the course and transport difficulties. Of the 43 patients randomized to the intervention group, 28 attended the pre-operative pain self-management sessions and 11 attended the post-operative sessions. Participant satisfaction with the course was high, and feedback highlighted that patients enjoyed the group format. Retention of participants was acceptable (83% of recruited patients completed follow-up) and questionnaire return rates were high (72% to 93%), with the exception of the pre-operative resource-use diary (35% return rate). Resource-use completion rates allowed for an economic evaluation from the health and social care payer perspective.Conclusions: This study highlights the importance of feasibility work prior to a randomized controlled trial to assess recruitment methods and rates, barriers to participation, logistics of scheduling group-based interventions, acceptability of the intervention and piloting resource use questionnaires to improve data available for economic evaluations. This information is of value to researchers and funders in the design and commissioning of future research.Trial registration: Current Controlled Trials ISRCTN52305381. © 2014 Wylde et al.; licensee BioMed Central Ltd