Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes

Background Despite the number of medications for type 2 diabetes, many people with the condition do not achieve good glycaemic control. Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most patients require treatment with combinations of glucose-lowering agents. The sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of glucose-lowering agents. Objective To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. Data sources MEDLINE, Embase, Cochrane Library (all sections); Science Citation Index; trial registries; conference abstracts; drug regulatory authorities; bibliographies of retrieved papers. Inclusion criteria Randomised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy. Methods Systematic review. Quality assessment used the Cochrane risk of bias score. Results Seven trials, published in full, assessed dapagliflozin and one assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced HbA1c by −0.54% (weighted mean differences (WMD), 95% CI −0.67 to −0.40) compared to placebo, but there was no difference compared to glipizide. Canagliflozin reduced HbA1c slightly more than sitagliptin (up to −0.21% vs sitagliptin). Both dapagliflozin and canagliflozin led to weight loss (dapagliflozin WMD −1.81 kg (95% CI −2.04 to −1.57), canagliflozin up to −2.3 kg compared to placebo). Limitations Long-term trial extensions suggested that effects were maintained over time. Data on canagliflozin are currently available from only one paper. Costs of the drugs are not known so cost-effectiveness cannot be assessed. More data on safety are needed, with the Food and Drug Administration having concerns about breast and bladder cancers. Conclusions Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes, although more safety data are needed

The Evolution of X-ray Bursts in the "Bursting Pulsar" GRO J1744-28

GRO J1744-28, commonly known as the `Bursting Pulsar', is a low mass X-ray binary containing a neutron star and an evolved giant star. This system, together with the Rapid Burster (MXB 1730-33), are the only two systems that display the so-called Type II X-ray bursts. These type of bursts, which last for 10s of seconds, are thought to be caused by viscous instabilities in the disk; however the Type II bursts seen in GRO J1744-28 are qualitatively very different from those seen in the archetypal Type II bursting source the Rapid Burster. To understand these differences and to create a framework for future study, we perform a study of all X-ray observations of all 3 known outbursts of the Bursting Pulsar which contained Type II bursts, including a population study of all Type II X-ray bursts seen by RXTE. We find that the bursts from this source are best described in four distinct phenomena or `classes' and that the characteristics of the bursts evolve in a predictable way. We compare our results with what is known for the Rapid Burster and put out results in the context of models that try to explain this phenomena.Comment: Accepted to MNRAS Aug 17 201

The Jefferson Lab Frozen Spin Target

A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200--300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin-lattice relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.Comment: 11 pages, 12 figures, preprint submitted to Nuclear Instruments and Methods in Physics Research, Section

Unicondylar fractures of the distal femur

AbstractBackgroundUnicondylar fractures of the distal femur are rare, complex, intra-articular fractures. The objective of this multicentre study was to assess the reduction and fixation of unicondylar fractures.HypothesisAnatomic reduction followed by strong fixation allows early rehabilitation therapy and provides good long-term outcomes.Material and methodsWe studied 163 fractures included in two multicentre studies, of which one was retrospective (n=134) and the other prospective (n=29). Follow-up of at least 1 year was required for inclusion. The treatment was at the discretion of the surgeon. Outcome measures were the clinical results assessed using the International Knee Society (IKS) scores and presence after fracture healing of malunion with angulation, an articular surface step-off, and/or tibio-femoral malalignment.ResultsMean age of the study patients was 50.9±24 years, and most patients were males with no previous history of knee disorders. The fracture was due to a high-energy trauma in 51% of cases; 17% of patients had compound fractures and 44% multiple fractures or injuries. The lateral and medial condyles were equally affected. The fracture line was sagittal in 82% of cases and coronal (Hoffa fracture) in 18% of cases. Non-operative treatment was used in 5% of cases and internal fixation in 95% of cases, with either direct screw or buttress-plate fixation for the sagittal fractures and either direct or indirect screw fixation for the coronal fractures. After treatment of the fracture, 15% of patients had articular malunion due to insufficient reduction, with either valgus-varus (10%) or flexion-recurvatum (5%) deformity; and 12% of patients had an articular step-off visible on the antero-posterior or lateral radiograph. Rehabilitation therapy was started immediately in 65% of patients. Time to full weight bearing was 90 days and time to fracture healing 120 days. Complications consisted of disassembly of the construct (2%), avascular necrosis of the condyle (2%), and arthrolysis (5%). The material was removed in 11% of patients. At last follow-up, the IKS knee score was 71±20 and the IKS function score 64±7; flexion range was 106±28° (<90° in 27% of patients); and 12% of patients had knee osteoarthritis.ConclusionAnatomic reduction of unicondylar distal femoral fractures via an appropriate surgical approach, followed by stable internal fixation using either multiple large-diameter screws or a buttress-plate, allows immediate mobilisation, which in turn ensures good long-term outcomes.Level of evidenceIV, cohort study

A systematic review of the energy and climate impacts of teleworking

Information and communication technologies (ICTs) increasingly enable employees to work from home and other locations (‘teleworking’). This study explores the extent to which teleworking reduces the need to travel to work and the consequent impacts on economy-wide energy consumption. Methods/Design: The paper provides a systematic review of the current state of knowledge of the energy impacts of teleworking. This includes the energy savings from reduced commuter travel and the indirect impacts on energy consumption associated with changes in non-work travel and home energy consumption. The aim is to identify the conditions under which teleworking leads to a net reduction in economy-wide energy consumption, and the circumstances where benefits may be outweighed by unintended impacts. The paper synthesises the results of 39 empirical studies, identified through a comprehensive search of 9,000 published articles. Review results/Synthesis: Twenty six of the 39 studies suggest that teleworking reduces energy use, and only eight studies suggest that teleworking increases, or has a neutral impact on energy use. However, differences in the methodology, scope and assumptions of the different studies make it difficult to estimate ‘average’ energy savings. The main source of savings is the reduced distance travelled for commuting, potentially with an additional contribution from lower office energy consumption. However, the more rigorous studies that include a wider range of impacts (e.g. non-work travel or home energy use) generally find smaller savings. Discussion: Despite the generally positive verdict on teleworking as an energy-saving practice, there are numerous uncertainties and ambiguities about its actual or potential benefits. These relate to the extent to which teleworking may lead to unpredictable increases in non-work travel and home energy use that may outweigh the gains from reduced work travel. The available evidence suggests that economy-wide energy savings are typically modest, and in many circumstances could be negative or non-existent

A GPU-based finite-size pencil beam algorithm with 3D-density correction for radiotherapy dose calculation

Targeting at the development of an accurate and efficient dose calculation engine for online adaptive radiotherapy, we have implemented a finite size pencil beam (FSPB) algorithm with a 3D-density correction method on GPU. This new GPU-based dose engine is built on our previously published ultrafast FSPB computational framework [Gu et al. Phys. Med. Biol. 54 6287-97, 2009]. Dosimetric evaluations against Monte Carlo dose calculations are conducted on 10 IMRT treatment plans (5 head-and-neck cases and 5 lung cases). For all cases, there is improvement with the 3D-density correction over the conventional FSPB algorithm and for most cases the improvement is significant. Regarding the efficiency, because of the appropriate arrangement of memory access and the usage of GPU intrinsic functions, the dose calculation for an IMRT plan can be accomplished well within 1 second (except for one case) with this new GPU-based FSPB algorithm. Compared to the previous GPU-based FSPB algorithm without 3D-density correction, this new algorithm, though slightly sacrificing the computational efficiency (~5-15% lower), has significantly improved the dose calculation accuracy, making it more suitable for online IMRT replanning

Twenty-First Century Climate Change and Submerged Aquatic Vegetation in a Temperate Estuary: The Case of Chesapeake Bay

Introduction: The Chesapeake Bay was once renowned for expansive meadows of submerged aquatic vegetation (SAV). However, only 10% of the original meadows survive. Future restoration effortswill be complicated by accelerating climate change, including physiological stressors such as a predicted mean temperature increase of 2-6°C and a 50-160% increase in CO2 concentrations. Outcomes: As the Chesapeake Bay begins to exhibit characteristics of a subtropical estuary, summer heat waves will become more frequent and severe. Warming alone would eventually eliminate eelgrass (Zostera marina) from the region. It will favor native heat-tolerant species such as widgeon grass (Ruppia maritima) while facilitating colonization by non-native seagrasses (e.g., Halodule spp.). Intensifying human activity will also fuel coastal zone acidification and the resulting high CO2/low pH conditions may benefit SAV via a CO2 fertilization effect. . Discussion: Acidification is known to offset the effects of thermal stress and may have similar effects in estuaries, assuming water clarity is sufficient to support CO2-stimulated photosynthesis and plants are not overgrown by epiphytes. However, coastal zone acidification is variable, driven mostly by local biological processes that may or may not always counterbalance the effects of regional warming. This precarious equipoise between two forces - thermal stress and acidification - will be critically important because it may ultimately determine the fate of cool-water plants such as Zostera marina in the Chesapeake Bay. Conclusion: The combined impacts of warming, coastal zone acidification, water clarity, and overgrowth of competing algae will determine the fate of SAV communities in rapidly changing temperate estuaries

Integration of professional judgement and decision-making in high-level adventure sports coaching practice

This study examined the integration of professional judgement and decision-making processes in adventure sports coaching. The study utilised a thematic analysis approach to investigate the decision-making practices of a sample of high-level adventure sports coaches over a series of sessions. Results revealed that, in order to make judgements and decisions in practice, expert coaches employ a range of practical and pedagogic management strategies to create and opportunistically use time for decision-making. These approaches include span of control and time management strategies to facilitate the decision-making process regarding risk management, venue selection, aims, objectives, session content, and differentiation of the coaching process. The implication for coaches, coach education, and accreditation is the recognition and training of the approaches that“create time” for the judgements in practice, namely“creating space to think”. The paper concludes by offering a template for a more expertise-focused progression in adventure sports coachin

Personalised service? Changing the role of the government librarian

Investigates the feasibility of personalised information service in a government department. A qualitative methodology explored stakeholder opinions on the remit, marketing, resourcing and measurement of the service. A questionnaire and interviews gathered experiences of personalised provision across the government sector. Potential users were similarly surveyed to discuss how the service could meet their needs. Data were analysed using coding techniques to identify emerging theory. Lessons learned from government librarians centred on clarifying requirements, balancing workloads and selective marketing. The user survey showed low usage and awareness of existing specialist services, but high levels of need and interest in services repackaged as a tailored offering. Fieldwork confirmed findings from the literature on the scope for adding value through information management advice, information skills training and substantive research assistance and the need to understand business processes and develop effective partnerships. Concluding recommendations focus on service definition, strategic marketing, resource utilisation and performance measurement

Veils, Crucifixes, and the Public Sphere: What Kind of Secularism? Rethinking Neutrality in a Post-Secular Europe

The Lautsi case in Italy attracted widespread attention in Europe and beyond. Though the issue under contention was a Christian symbol, the European Court of Human Rights (ECHR) judgements showed changes in assessment both about religion (in contrast with former cases regarding Muslim veils) and secularism (which did not have the same meaning for everyone). In light of those rulings, this paper reflects on the concepts of neutrality and secularism and their normative implications for European citizens in terms of belonging, solidarity and cohesion. An open and plural public sphere, in which intercultural exchange can flourish, is crucial if Europe is serious about the integration of its immigrants, many of whom possess a Muslim background. A ‘post-secular’ Europe may have to reconsider long-held stereotypes about religion and nuance its self-understanding as ‘secular’, in a way that religious citizens can identify with Europe too. The discussion will draw on the ideas of Taylor, Casanova, Habermas, Weiler and Beck to illustrate some of the political, ethical and theoretical complexities of the Lautsi case, specifically issues to do with neutrality, secularism and the role of religion in the public sphere