Modelling the Milky Way's globular cluster system

We construct a model for the Galactic globular cluster system based on a realistic gravitational potential and a distribution function (DF) analytic in the action integrals. The DF comprises disc and halo components whose functional forms resemble those recently used to describe the stellar discs and stellar halo. We determine the posterior distribution of our model parameters using a Bayesian approach. This gives us an understanding of how well the globular cluster data constrain our model. The favoured parameter values of the disc and halo DFs are similar to values previously obtained from fits to the stellar disc and halo, although the cluster halo system shows clearer rotation than does the stellar halo. Our model reproduces the generic features of the globular cluster system, namely the density profile, the mean rotation velocity. The fraction of disc clusters coincides with the observed fraction of metal-rich clusters. However, the data indicate either incompatibility between catalogued cluster distances and current estimates of distance to the Galactic Centre, or failure to identify clusters behind the bulge. As the data for our Galaxy's components increase in volume and precision over the next few years, it will be rewarding to revisit the present analysis.Comment: 13 pages accepted by MNRA

Treatment for inclusion body myositis

Background Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects of treatment for IBM. Search methods On 7 October 2014 we search ed the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials. Selection criteria We considered randomised or quasi-randomised trials, including cross-over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews. Data collection and analysis We used standard Cochrane methodological procedures. Main results The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events. Authors\u27 conclusions Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures

Toward Assessment of Lung Water Content Using Wireless Cardio-Pulmonary Stethoscope Measurements

M.S

Development of a universal benefit-risk assessment framework and its application for regulatory agencies

The assessment of medicines has moved from efficacy and safety to that of a benefit-risk balance and regulatory agencies and pharmaceutical companies are improving their processes in order to achieve greater consistency and transparency in decision-making. However, their efforts are largely independent and do not address the lack of consistency in decisions by different countries, albeit for the same medicine, resulting in the potential inaccessibility of important medicines. The aim of this study was the development and validation of a universal benefit-risk framework for use by regulatory authorities. A questionnaire, specifically developed for this study, was used to evaluate the current approaches to benefit-risk assessment of medicines by 14 regulatory agencies and 24 pharmaceutical companies. None of the 11 agencies (79%) and 20 companies (83%) that responded used a fully quantitative approach, but the majority used a qualitative system for benefit-risk assessment. The development of a universal benefit-risk framework for use by both regulators and industry, with the involvement of all stakeholders, was supported by the study participants. A comparison of the existing benefit-risk assessment frameworks used by agencies and companies identified the common elements. As no major differences were observed, an 8-step universal framework was developed which incorporated the other frameworks. To support the framework in the assessment of benefits and risks, a template for documenting the benefit-risk decision together with a user manual was also developed. Four regulatory agencies conducted a retrospective pilot study to investigate the feasibility of this framework, the benefit-risk template and user manual. Subsequently, a prospective study was conducted by TGA of Australia, Health Canada and HSA of Singapore. The agencies found the benefit-risk template was ‘fit for purpose’ in terms of the relevance of information supporting the benefit-risk decision, the documentation and communication and the relative importance and values of the benefits and risks. The results showed that the benefit-risk summary template was adequate to document benefits and risks, relevant summaries and ii conclusions for the emerging markets. The applicability and validity of the summary component of the benefit-risk template was evaluated by sixteen HSA clinical reviewers in a retrospective study. They found that the BR Summary Template was adequate to document benefits, risks, relevant summaries and conclusions. However, a revision of the BR Summary Template should include technical improvements and more details of safety information. The BR Summary Template was thought to be a useful tool for communicating benefit-risk decisions to a variety of stakeholders. The formats of publicly available reports from major regulatory agencies were compared and found to be generally similar. When compared to the BR Template, the listing of benefits and risks, assigning of weights and values, visualisation and a more detailed, systematic standardised structure were found to be absent. This research has demonstrated that the 8-step universal framework is of value for the assessment of benefits and risks of medicines by regulatory agencies and the template was found to be useful for documenting and communicating benefit-risk decisions

High power and ultra-low-noise photodetector for squeezed-light enhanced gravitational wave detectors

Current laser-interferometric gravitational wave detectors employ a self-homodyne readout scheme where a comparatively large light power (5–50 mW) is detected per photosensitive element. For best sensitivity to gravitational waves, signal levels as low as the quantum shot noise have to be measured as accurately as possible. The electronic noise of the detection circuit can produce a relevant limit to this accuracy, in particular when squeezed states of light are used to reduce the quantum noise. We present a new electronic circuit design reducing the electronic noise of the photodetection circuit in the audio band. In the application of this circuit at the gravitational-wave detector GEO 600 the shot-noise to electronic noise ratio was permanently improved by a factor of more than 4 above 1 kHz, while the dynamic range was improved by a factor of 7. The noise equivalent photocurrent of the implemented photodetector and circuit is about 5 µA/ √\ud Hz above 1 kHz with a maximum detectable photocurrent of 20 mA. With the new circuit, the observed squeezing level in GEO 600 increased by 0.2 dB. The new circuit also creates headroom for higher laser power and more squeezing to be observed in the future in GEO 600 and is applicable to other optics experiments