Hystricognathy vs Sciurognathy in the Rodent Jaw: A New Morphometric Assessment of Hystricognathy Applied to the Living Fossil Laonastes (Diatomyidae)

While exceptional for an intense diversification of lineages, the evolutionary history of the order Rodentia comprises only a limited number of morphological morphotypes for the mandible. This situation could partly explain the intense debates about the taxonomic position of the latest described member of this clade, the Laotian rock rat Laonastes aenigmamus (Diatomyidae). This discovery has re-launched the debate on the definition of the Hystricognathi suborder identified using the angle of the jaw relative to the plane of the incisors. Our study aims to end this ambiguity. For clarity, it became necessary to revisit the entire morphological diversity of the mandible in extant and extinct rodents. However, current and past rodent diversity brings out the limitations of the qualitative descriptive approach and highlights the need for a quantitative approach. Here, we present the first descriptive comparison of the masticatory apparatus within the Ctenohystrica clade, in combining classic comparative anatomy with morphometrical methods. First, we quantified the shape of the mandible in rodents using 3D landmarks. Then, the analysis of osteological features was compared to myological features in order to understand the biomechanical origin of this morphological diversity. Among the morphological variation observed, the mandible of Laonastes aenigmamus displays an intermediate association of features that could be considered neither as sciurognathous nor as hystricognathous

An extragalactic supernebula confined by gravity

Little is known about the origins of the giant star clusters known as globular clusters. How can hundreds of thousands of stars form simultaneously in a volume only a few light years across the distance of the sun to its nearest neighbor? Radiation pressure and winds from luminous young stars should disperse the star-forming gas and disrupt the formation of the cluster. Globular clusters in our Galaxy cannot provide answers; they are billions of years old. Here we report the measurement of infrared hydrogen recombination lines from a young, forming super star cluster in the dwarf galaxy, NGC 5253. The lines arise in gas heated by a cluster of an estimated million stars, so young that it is still enshrouded in gas and dust, hidden from optical view. We verify that the cluster contains 4000-6000 massive, hot "O" stars. Our discovery that the gases within the cluster are bound by gravity may explain why these windy and luminous O stars have not yet blown away the gases to allow the cluster to emerge from its birth cocoon. Young clusters in "starbursting" galaxies in the local and distant universe may be similarly gravitationally confined and cloaked from view.Comment: Letter to Natur

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

Interaction effects of region-level GDP per capita and age on labour market transition rates in Italy

Abstract The aim of this paper is to measure the effect of the interaction between age for the population of males and females aged 18 to 74 and region-level GDP per capita on labour market transition probabilities in Italy. We compare different occupational states in a sample of males and females who remained in their region of residence at two points in time (12 months apart). We estimate the transition probabilities using a flexible hierarchical logit model with interaction effects between worker age and region-level GDP per capita. We apply this model using longitudinal data from the Italian Labour Force Survey that cover the 2004–2013 period. We find empirical support for the assumption that people in the same age cohort have different labour market opportunities based on the level of GDP per capita in their region of residence. These differences are particularly relevant among younger workers

The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial

Background: GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include ‘G’ and ‘liquid ecstasy’. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to ‘come down’ after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency /intensive care unit. The GABAB receptor mediates most effects of GHB/GBL and the GABAB agonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day ‘preload’ prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further. Methods/design: This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL- dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness. Discussion: This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal

Recovery in Psychosis from a Service User Perspective: A Systematic Review and Thematic Synthesis of Current Qualitative Evidence

There is a growing number of qualitative accounts regarding recovery from psychosis from a service user perspective. The aim of this study was to conduct a systematic review of these qualitative accounts. A thematic synthesis was utilised to synthesise and analyse seventeen studies included in the review. Studies were included if they used a qualitative methodology to explore service users’ experiences of recovery from psychosis as a primary research question. All included studies were subjected to a quality assessment. The analysis outlined three subordinate themes: the recovery journey, facilitators of recovery (e.g. faith and spirituality, personal agency and hope), and barriers to recovery (e.g. stigma and discrimination, negative effects of mental health services and medication). Recovery is an idiosyncratic process but includes key components which are important to people who experience psychosis. These should be explored within clinical practice