General practitioners' reasons for removing patients from their lists: postal survey in England and Wales

The removal of patients from doctors' lists causes con­ siderable public and political concern, with speculation that patients are removed for inappropriate, including financial, reasons. In 1999 the House of Commons Select Committee on Public Administration noted that little evidence was available on either the frequency of, or the reasons for, removal of patients. National statistics do not distinguish between patients removed after moving out of a practice area and those removed for other reasons. Two postal surveys have reported why general practitioners might, in general, remove patients, and one small study has described the reasons doctors give for particular removals. We therefore determined the current scale of, and doctors' reasons for, removal of patients from their lists in Eng­ land and Wales

PS16dtm: A Tidal Disruption Event in a Narrow-line Seyfert 1 Galaxy

[Abridged] We present observations of PS16dtm, a luminous transient that occurred at the nucleus of a known Narrow-line Seyfert 1 galaxy hosting a 10$^6$ M$_\odot$ black hole. The transient was previously claimed to be a Type IIn SLSN due to its luminosity and hydrogen emission lines. The light curve shows that PS16dtm brightened by about two magnitudes in ~50 days relative to the archival host brightness and then exhibited a plateau phase for about 100 days followed by the onset of fading in the UV. During the plateau PS16dtm showed no color evolution, maintained a blackbody temperature of 1.7 x 10$^4$ K, and radiated at approximately $L_{Edd}$ of the SMBH. The spectra exhibit multi-component hydrogen emission lines and strong FeII emission, show little evolution with time, and closely resemble the spectra of NLS1s while being distinct from those of Type IIn SNe. Moreover, PS16dtm is undetected in the X-rays to a limit an order of magnitude below an archival X-ray detection of its host galaxy. These observations strongly link PS16dtm to activity associated with the SMBH and are difficult to reconcile with a SN origin or any known form of AGN variability, and therefore we argue that it is a TDE in which the accretion of the stellar debris powers the rise in the continuum and excitation of the pre-existing broad line region, while providing material that obscures the X-ray emitting region of the pre-existing AGN accretion disk. A detailed TDE model fit to the light curve indicates that PS16dtm will remain bright for several years; we further predict that the X-ray emission will reappear on a similar timescale as the accretion rate declines. Finally, we place PS16dtm in the context of other TDEs and find that TDEs in AGN galaxies are an order of magnitude more efficient and reach Eddington luminosities, likely due to interaction of the stellar debris with the pre-existing accretion disk.Comment: 19 pages, 17 figures, Submitted to Ap

A re-examination of the anatomy and systematics of the tomistomine crocodylians from the Miocene of Italy and Malta

Once a much more globally widespread crocodylian clade, Tomistominae is today represented by just one species, Tomistoma schlegelii (the false gharial), restricted to south-east Asia. Although tomistomine fossil occurrences are recognized from the early Eocene (∼55 Ma) onwards, their remains are often incomplete, making appropriate taxonomic classification within the group problematic. This is especially pertinent to several taxa from the Miocene of Europe, which were historically erected from fragmentary remains. Here we re-examine and describe four approximately contemporaneous taxa from Malta and Italy to determine their taxonomy and phylogenetic affinities: Melitosaurus champsoides, Tomistoma calaritanum, Tomistoma gaudense and Tomistoma lyceense. We place them into a phylogenetic analysis for the first time, comprising 70 taxa scored for 244 characters, several of which are revised or novel, and apply a number of character weighting strategies. Whereas ‘Tomistoma lyceense’ is deemed to be an indeterminate tomistomine, a unique combination of features confirms Melitosaurus champsoides, Tomistoma calaritanum and Tomistoma gaudense as three distinct species. These three taxa are recovered as derived tomistomines, with characters such as a posterior maxillary process between the lacrimal and nasal, large supratemporal fenestrae that are wider than long, and the posteromedial alignment of the last three premaxillary teeth, suggesting a close relationship with the approximately contemporaneous European taxa, Tomistoma lusitanica and Gavialosuchus eggenburgensis. It is unlikely that any of these species belong to Tomistoma, with the possibility that they can all be classified under Melitosaurus and Gavialosuchus. However, we retain them in open nomenclature pending reassessment of the remaining European Miocene tomistomines. Our taxonomic and phylogenetic revision helps to elucidate past tomistomine diversity in the Miocene of the Mediterranean region, prior to the group’s extirpation, and is an important first step in resolving the complicated history of European tomistomine systematics

Reporting issues in group sequential randomised controlled trials: a systematic review protocol of published journal reports

Background: Adaptive designs are somewhat underused, despite prominence given to methodology in the statistical literature. Some concerns relates to robustness of adaptive designs in decision making, acceptability of trial findings to change practice, anxiety about early stopping of trials and worry about wrong decision making. These issues could be linked to inadequate reporting of the conduct of such clinical trials. We assess the reporting of group sequential randomised controlled trials (RCTs), which are one of the most well-understood adaptive designs in the confirmatory setting. Methods: We undertake a systematic review searching Ovid MEDLINE from 1st January 2001 to 23rd September 2014 and including parallel group confirmatory group sequential RCTs that were prospectively designed using the Frequentist approach. Eligible trials are screened for completeness in reporting against the CONSORT 2010 checklist with some proposed modifications to capture issues such as statistical bias correction following early stopping. Descriptive statistics aided with forest plots on CONSORT compliance are presented. Discussion: Reporting of the conduct of adaptive designs is an area which has not been fully explored. Hence, the findings from this study can enlighten us on the adequacy in reporting of well-understood group sequential RCTs as a class of adaptive designs and on ways to address some of the cited concerns. Most importantly, the study can inform policy makers on the adequacy of the current CONSORT statements in enhancing reporting of such adaptive designs

Sphingosine-1-phosphate–induced smooth muscle cell migration involves the mammalian target of rapamycin

BackgroundVascular smooth muscle cell (SMC) migration is an important component of the development of intimal hyperplasia. Sphingosine-1-phosphate (S-1-P) is a lipid released from activated platelets with numerous cellular effects including the stimulation of SMC migration in vitro. We examined the role of the mammalian target of rapamycin and ribosomal p70S6 kinase (p70S6K) in S-1-P–induced SMC migration.MethodsRat arterial SMCs were cultured in vitro. Linear wound and Boyden microchemotaxis assays of migration were performed in the presence of S-1-P (0.01 to 100 μmol/L) with and without rapamycin (10 nmol/L). Western blotting was performed for phosphorylated and total p70S6K, ERK1/2, and p38MAPK after stimulation with S-1-P (0.1 μmol/L), with and without rapamycin pretreatment. Phosphorylation of p70S6K was also assayed after S-1-P treatment in the presence and absence of inhibitors of PI3 kinase (wortmannin, WN, and LY294002, LY), Akt (AktI), p38MAPK (SB203580), and MEK1 (PD98059).ResultsS-1-P stimulated migration of SMCs in both linear wound and Boyden chamber assays compared to control (P < .05); these responses were inhibited by rapamycin to below the level of control (P < .05 vs S-1-P alone for both assays) in a dose-dependent manner (inhibitory concentration of 50%, 10 nmol/L). S-1-P stimulated phosphorylation of ERK1/2, p38MAPK, and p70S6K, which peaked at 5 minutes for ERK1/2 and p38MAPK and10 minutes for p70S6K (2-fold increase over control for each, P < .05). Rapamycin prevented the phosphorylation of p70S6K at the Thr 389 site (which correlates with enzyme activity), reduced ERK1/2 phosphorylation, but had no effect on the Thr 421/Ser 424 site or on p38MAPK phosphorylation. Wortmannin and LY294002 inhibited phosphorylation of the Thr 389 site of p70S6K. AktI and SB203580 had no effect on p70S6K, whereas PD98059 had a marginal effect.ConclusionsS-1-P–induced SMC migration was completely inhibited by rapamycin, indicating that the p70S6K pathway is involved. This mechanism likely involves modulation of the ERK1/2 pathway. S-1-P stimulates phosphorylation of p70S6K in a MEK1-dependent, PI3 kinase–dependent, but Akt-independent manner.Clinical relevanceS-1-P is released from activated platelets at sites of vessel injury and contributes to the development of intimal hyperplasia after bypass grafting, angioplasty, and stenting. S-1-P is a potent pro-migratory molecule for SMCs. Rapamycin is a commonly used immunosuppressive agent that has most recently been incorporated as the biologic agent in drug eluting stents with good success in the coronary circulation. Rapamycin inhibits the mammalian target of rapamycin, which, in turn, controls the translational mechanisms of the cell. The role of translational control during S-1-P–induced SMC migration is poorly understood. This study identifies a link between the mammalian target of rapamycin translational pathway and S-1-P and demonstrates how rapamycin might interfere with another facet of a vessel's response to injury after a vascular intervention, namely by interfering with the cell signaling of factors released from platelets deposited at the injury site

The host galaxy and late-time evolution of the Super-Luminous Supernova PTF12dam

Super-luminous supernovae of type Ic have a tendency to occur in faint host galaxies which are likely to have low mass and low metallicity. PTF12dam is one of the closest and best studied super-luminous explosions that has a broad and slowly fading lightcurve similar to SN 2007bi. Here we present new photometry and spectroscopy for PTF12dam from 200-500 days (rest-frame) after peak and a detailed analysis of the host galaxy (SDSS J142446.21+461348.6 at z = 0.107). Using deep templates and image subtraction we show that the full lightcurve can be fit with a magnetar model if escape of high-energy gamma rays is taken into account. The full bolometric lightcurve from -53 to +399 days (with respect to peak) cannot be fit satisfactorily with the pair-instability models. An alternative model of interaction with a dense CSM produces a good fit to the data although this requires a very large mass (~ 13 M_sun) of hydrogen free CSM. The host galaxy is a compact dwarf (physical size ~ 1.9 kpc) and with M_g = -19.33 +/- 0.10, it is the brightest nearby SLSN Ic host discovered so far. The host is a low mass system (2.8 x 10^8 M_sun) with a star-formation rate (5.0 M_sun/year), which implies a very high specific star-formation rate (17.9 Gyr^-1). The remarkably strong nebular lines provide detections of the [O III] \lambda 4363 and [O II] \lambda\lambda 7320,7330 auroral lines and an accurate oxygen abundance of 12 + log(O/H) = 8.05 +/- 0.09. We show here that they are at the extreme end of the metallicity distribution of dwarf galaxies and propose that low metallicity is a requirement to produce these rare and peculiar supernovae.Comment: 20 pages, 12 figures, 8 tables, accepted for publication to MNRA

A systematic review of naturalistic interventions in refugee populations

Naturalistic interventions with refugee populations examine outcomes following mental health interventions in existing refugee service organisations. The current review aimed to examine outcomes of naturalistic interventions and quality of the naturalistic intervention literature in refugee populations with the view to highlight the strengths and limitations of naturalistic intervention studies. Database search was conducted using the search terms ‘refugee’, ‘asylum seeker’, ‘treatment’, ‘therapy’ and ‘intervention. No date limitations were applied, but searches were limited to articles written in English. Seven studies were identified that assessed the outcome of naturalistic interventions on adult refugees or asylum seekers in a country of resettlement using quantitative outcome measures. Results showed significant variation in the outcomes of naturalistic intervention studies, with a trend towards showing decreased symptomatology at post-intervention. However, conclusions are limited by methodological problems of the studies reviewed, particularly poor documentation of intervention methods and lack of control in the design of naturalistic intervention studies. Further examination of outcomes following naturalistic interventions is needed with studies which focus on increasing the rigour of the outcome assessment process

MOSFiT: Modular open source fitter for transients

Much of the progress made in time-domain astronomy is accomplished by relating observational multi-wavelength time series data to models derived from our understanding of physical laws. This goal is typically accomplished by dividing the task in two: collecting data (observing), and constructing models to represent that data (theorizing). Owing to the natural tendency for specialization, a disconnect can develop between the best available theories and the best available data, potentially delaying advances in our understanding new classes of transients. We introduce MOSFiT: the Modular Open-Source Fitter for Transients, a Python-based package that downloads transient datasets from open online catalogs (e.g., the Open Supernova Catalog), generates Monte Carlo ensembles of semi-analytical light curve fits to those datasets and their associated Bayesian parameter posteriors, and optionally delivers the fitting results back to those same catalogs to make them available to the rest of the community. MOSFiT is designed to help bridge the gap between observations and theory in time-domain astronomy; in addition to making the application of existing models and creation of new models as simple as possible, MOSFiT yields statistically robust predictions for transient characteristics, with a standard output format that includes all the setup information necessary to reproduce a given result. As large-scale surveys such as LSST discover entirely new classes of transients, tools such as MOSFiT will be critical for enabling rapid comparison of models against data in statistically consistent, reproducible, and scientifically beneficial ways