What are the participants’ perspectives of taking melatonin for the treatment of nocturia in Multiple Sclerosis? -a qualitative study embedded within a double blind RCT

Background: Multiple Sclerosis (MS) is a chronic neurological disorder caused by neurodegeneration within the central nervous system. It results in impaired physical, cognitive and psychological functioning and can also lead to lower urinary tract symptoms including nocturia. While clinical trials have suggested an association between nocturia and melatonin secretion, to our knowledge, no qualitative research has been conducted on the experience of taking melatonin to treat nocturia in progressive MS within a clinical trial. Methods: 17 semi-structured qualitative interviews were conducted as part of a double-blind, randomised, placebo controlled, crossover, clinical trial with consenting adults with MS. Interviews explored participants’ experiences of nocturia associated with MS and their experience of taking melatonin as a trial treatment for nocturia versus a placebo. Data was analysed using a thematic analysis. Results: Themes on the experience of nocturia revealed participants’ understandings of nocturia, the impact it had on their night and increased daily fatigue. Themes on the intervention showed perceived improvements to nocturia, sleep and energy and negative effects including lethargy, a lack of significant change and physical side effects including vivid dreams.Conclusion: This qualitative exploration revealed an association between nocturia and increased levels of fatigue during the day by those with MS. However, perspectives towards the effectiveness of melatonin as a potential treatment varied as both placebo and melatonin were perceived as having very similar effects

Melting as a String-Mediated Phase Transition

We present a theory of the melting of elemental solids as a dislocation-mediated phase transition. We model dislocations near melt as non-interacting closed strings on a lattice. In this framework we derive simple expressions for the melting temperature and latent heat of fusion that depend on the dislocation density at melt. We use experimental data for more than half the elements in the Periodic Table to determine the dislocation density from both relations. Melting temperatures yield a dislocation density of (0.61\pm 0.20) b^{-2}, in good agreement with the density obtained from latent heats, (0.66\pm 0.11) b^{-2}, where b is the length of the smallest perfect-dislocation Burgers vector. Melting corresponds to the situation where, on average, half of the atoms are within a dislocation core.Comment: 18 pages, LaTeX, 3 eps figures, to appear in Phys. Rev.

Crystalline Order on a Sphere and the Generalized Thomson Problem

We attack generalized Thomson problems with a continuum formalism which exploits a universal long range interaction between defects depending on the Young modulus of the underlying lattice. Our predictions for the ground state energy agree with simulations of long range power law interactions of the form 1/r^{gamma} (0 < gamma < 2) to four significant digits. The regime of grain boundaries is studied in the context of tilted crystalline order and the generality of our approach is illustrated with new results for square tilings on the sphere.Comment: 4 pages, 5 eps figures Fig. 2 revised, improved Fig. 3, reference typo fixe

Socio-economic utility and chemical potential

In statistical physics, the conservation of particle number results in the equalization of the chemical potential throughout a system at equilibrium. In contrast, the homogeneity of utility in socio-economic models is usually thought to rely on the competition between individuals, leading to Nash equilibrium. We show that both views can be reconciled by introducing a notion of chemical potential in a wide class of socio-economic models, and by relating it in a direct way to the equilibrium value of the utility. This approach also allows the dependence of utility across the system to be determined when agents take decisions in a probabilistic way. Numerical simulations of a urban economic model also suggest that our result is valid beyond the initially considered class of solvable models.Comment: 6 pages, 3 figures, final versio

Synoptic conditions conducive for compound wind-flood events in Great Britain in present and future climates

Extreme wind is the main driver of loss in North-West Europe, with flooding being the second-highest driver. These hazards are currently modelled independently, and it is unclear what the contribution of their co-occurrence is to loss. They are often associated with extra-tropical cyclones, with studies focusing on co-occurrence of extreme meteorological variables. However, there has not been a systematic assessment of the meteorological drivers of the co-occurring \textit{impacts} of compound wind-flood events. This study quantifies this using an established storm severity index (SSI) and recently developed flood severity index (FSI), applied to the UKCP18 12km regional climate simulations, and a Great Britain (GB) focused hydrological model. The meteorological drivers are assessed using 30 weather types, which are designed to capture a broad spectrum of GB weather. Daily extreme compound events (exceeding 99th percentile of both SSI and FSI) are generally associated with cyclonic weather patterns, often from the positive phase of the North Atlantic Oscillation (NAO+) and Northwesterly classifications. Extreme compound events happen in a larger variety of weather patterns in a future climate. The location of extreme precipitation events shifts southward towards regions of increased exposure. The risk of extreme compound events increases almost four-fold in the UKCP18 simulations (from 14 events in the historical period, to 55 events in the future period). It is also more likely for there to be multi-day compound events. At seasonal timescales years tend to be either flood-prone or wind-damage-prone. In a future climate there is a larger proportion of years experiencing extreme seasonal SSI and FSI totals. This could lead to increases in reinsurance losses if not factored into current modelling

Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies

RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits in that model organism. We show here that ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded RNA targeting GFP or lacZ for degradation, or by increasing expression of Dicer substantially reduces lifespan in Drosophila melanogaster. Induction of GFPRNAi construct also alters the response of lifespan to nutrition, exacerbating the lifespan-shortening effects of food containing a high quantity of yeast. Our study indicates that activation of the RNAi machinery may have sequence-independent side-effects on lifespan, and that caution needs to be exercised when employing ubiquitous RNAi in Drosophila ageing studies. However, we also show that RNAi restricted to certain tissues may not be detrimental to lifespan

Refining and testing the diagnostic accuracy of an assessment tool (PAT-POPS) to predict admission and discharge of children and young people who attend an emergency department : protocol for an observational study

Background: Increasing attendances by children (aged 0–16 years) to United Kingdom Emergency Departments (EDs) challenges patient safety within the National Health Service (NHS) with health professionals required to make complex judgements on whether children attending urgent and emergency care services can be sent home safely or require admission. Health regulation bodies have recommended that an early identification systems should be developed to recognise children developing critical illnesses. The Pennine Acute Hospitals NHS Trust Paediatric Observation Priority Score (PAT-POPS) was developed as an ED-specific tool for this purpose. This study aims to revise and improve the existing tool and determine its utility in determining safe admission and discharge decision making. Methods/design: An observational study to improve diagnostic accuracy using data from children and young people attending the ED and Urgent Care Centre (UCC) at three hospitals over a 12 month period. The data being collected is part of routine practice; therefore opt-out methods of consent will be used. The reference standard is admission or discharge. A revised PAT-POPs scoring tool will be developed using clinically guided logistic regression models to explore which components best predict hospital admission and safe discharge. Suitable cut-points for safe admission and discharge will be established using sensitivity and specificity as judged by an expert consensus meeting. The diagnostic accuracy of the revised tool will be assessed, and it will be compared to the former version of PAT-POPS using ROC analysis. Discussion: This new predictive tool will aid discharge and admission decision-making in relation to children and young people in hospital urgent and emergency care facilities. Trial registration: NIHR RfPB Grant: PB-PG-0815-20034. ClinicalTrials.gov: 213469. Retrospectively registered on 11 April 2018. Keywords: Paediatric, Emergency department, Diagnostic accuracy, Early identification systems, screening tool, Observational, Early warning score, Early warning system, hospital admission

Dated Plant Phylogenies Resolve Neogene Climate and Landscape Evolution in the Cape Floristic Region

In the context of molecularly-dated phylogenies, inferences informed by ancestral habitat reconstruction can yield valuable insights into the origins of biomes, palaeoenvironments and landforms. In this paper, we use dated phylogenies of 12 plant clades from the Cape Floristic Region (CFR) in southern Africa to test hypotheses of Neogene climatic and geomorphic evolution. Our combined dataset for the CFR strengthens and refines previous palaeoenvironmental reconstructions based on a sparse, mostly offshore fossil record. Our reconstructions show remarkable consistency across all 12 clades with regard to both the types of environments identified as ancestral, and the timing of shifts to alternative conditions. They reveal that Early Miocene land surfaces of the CFR were wetter than at present and were dominated by quartzitic substrata. These conditions continue to characterize the higher-elevation settings of the Cape Fold Belt, where they have fostered the persistence of ancient fynbos lineages. The Middle Miocene (13-17 Ma) saw the development of perennial to weakly-seasonal arid conditions, with the strongly seasonal rainfall regime of the west coast arising ~6.5-8 Ma. Although the Late Miocene may have seen some exposure of the underlying shale substrata, the present-day substrate diversity of the CFR lowlands was shaped by Pliocene-Pleistocene events. Particularly important was renewed erosion, following the post-African II uplift episode, and the reworking of sediments on the coastal platform as a consequence of marine transgressions and tectonic uplift. These changes facilitated adaptive radiations in some, but not all, lineages studied

Androgen receptor genotyping in a large Australasian cohort with androgen insensitivity syndrome; identification of four novel mutations

We genotyped the androgen receptor (AR) gene in 31 Australasian patients with androgen insensitivity syndrome (AIS). The entire coding region of AR was examined including analysis of polymorphic CAG and GGN repeats in all patients. AR defects were found in 66.7% (6/9) of patients with complete AIS (CAIS) and 13.6% (3/22) of patients with partial AIS (PAIS). A novel deletion (N858delG) leading to a premature stop codon was found in CAIS patient P1. CAIS patient P2 has a novel deletion (N2676delGAGT) resulting in a stop at codon 787. These mutations would result in inactivation of AR protein. A novel insertion of a cysteine residue in the first zinc finger of the AR DNA-binding domain (N2045_2047dupCTG) was found in CAIS patient P3. PAIS patient P4 has a novel amino acid substitution (Arg760Ser) in the AR ligand binding domain, which may impair ligand binding. Five patients were found to have previously reported AR mutations and no mutations were identified in the remaining patients