Methamphetamine Induces Striatal Cell Death Followed by the Generation of New Cells and a Second Round of Cell Death in Mice

Our laboratory has been investigating the impact of a neurotoxic exposure to methamphetamine (METH) on cellular components of the striatum post-synaptic to the dopaminergic terminals. A systemic bolus injection of METH (30 mg/kg, ip) induces the production of new cells in the striatum during a period lasting from 24-48 hours after METH. The newly generated cells arise from dormant striatal progenitors and not from the subventricular zone. The newly generated cells display glial phenotypes and begin to die 24 hours after birth, or 2.5 days post-METH. The protracted phase of cell death lasts for at least three months post-METH at which time the bulk of the newly generated cells have disappeared. The METH-induced production of new cells is associated with enlarged striatal volume (up to 50% larger than controls in some animals). As the newly generated cells die over a period of three months, the enlarged striatal volume normalizes. In conclusion, a neurotoxic dose of METH induces the generation of new cells in the striatum associated with enlarged striatal volume. The new cells die over three months post-METH and the enlarged striatal volume returns to control levels. This observation is significant because studies involving METH users show striatal enlargement and the normalization of striatal volume in METH users who have been abstinent for up to 20 months

Tensile rotary power transmission model development for airborne wind energy systems

Rotary airborne wind energy (AWE) systems are a family of AWE devices that utilise networked kites to form rotors. One such device is the Daisy Kite developed by Windswept and Interesting. The Daisy Kite uses a novel tensile rotary power transmission (TRPT) to transfer power generated at the flying rotor down to the ground. Two dynamic models have been developed and compared; one with simple spring-disc representation, and one with multi-spring representation that can take account of more degrees of freedom. Simulation results show that the angular velocity responses of the two TRPT models are more closely correlated in higher wind speeds when the system shows stiffer torsional behaviour. Another interesting point is the observation of two equilibrium states, when the spring-disc TRPT model is coupled with NREL's AeroDyn. Given the computational efficiency of the simpler model and the high correlation of the results between the two models, the simple model can be used for more demanding simulations

StreetWise: developing a serious game to support forensic mental health service users’ preparation for discharge: a feasibility study

Forensic Mental Health [FMH] services are tasked with ensuring public safety whilst supporting service user recovery and reintegration into wider society. Due to past histories of offending behaviour, FMH service users are often detained under the Mental Health Act (2007) within secure settings where they are monitored and their freedom and self-governance is limited. Restricted community access makes risk assessment and skill development for community living problematic. The measures of control and security inherent within FMH services pose a challenge to social integration and recovery, whereby users feel empowered with self-efficacy to work towards their own goals with hope and optimism (Simpson & Penney, 2011). Additionally, detention in secure services leads to isolation from the community which adds risk and stigma to the complexity of the service users’ journey of recovery. This feasibility study explores how new technologies may be used to support FMH service users on their journey to recovery. A prototype serious game was co-produced with FMH service users with the aim of enabling service users to engage safely with community based scenarios and begin to develop skills for community living and consider self-management in risky situations whilst detained within a secure environment

Vortical and Wave Modes in 3D Rotating Stratified Flows: Random Large Scale Forcing

Utilizing an eigenfunction decomposition, we study the growth and spectra of energy in the vortical and wave modes of a 3D rotating stratified fluid as a function of $\epsilon = f/N$. Working in regimes characterized by moderate Burger numbers, i.e. $Bu = 1/\epsilon^2 < 1$ or $Bu \ge 1$, our results indicate profound change in the character of vortical and wave mode interactions with respect to $Bu = 1$. As with the reference state of $\epsilon=1$, for $\epsilon < 1$ the wave mode energy saturates quite quickly and the ensuing forward cascade continues to act as an efficient means of dissipating ageostrophic energy. Further, these saturated spectra steepen as $\epsilon$ decreases: we see a shift from $k^{-1}$ to $k^{-5/3}$ scaling for $k_f < k < k_d$ (where $k_f$ and $k_d$ are the forcing and dissipation scales, respectively). On the other hand, when $\epsilon > 1$ the wave mode energy never saturates and comes to dominate the total energy in the system. In fact, in a sense the wave modes behave in an asymmetric manner about $\epsilon = 1$. With regard to the vortical modes, for $\epsilon \le 1$, the signatures of 3D quasigeostrophy are clearly evident. Specifically, we see a $k^{-3}$ scaling for $k_f < k < k_d$ and, in accord with an inverse transfer of energy, the vortical mode energy never saturates but rather increases for all $k < k_f$. In contrast, for $\epsilon > 1$ and increasing, the vortical modes contain a progressively smaller fraction of the total energy indicating that the 3D quasigeostrophic subsystem plays an energetically smaller role in the overall dynamics.Comment: 18 pages, 6 figs. (abbreviated abstract

Risk, trust and patients’ strategic choices of healthcare practitioners

Research on patients’ choice of healthcare practitioners has focussed on countries with regulated and controlled healthcare markets. In contrast, low- and middle-income countries have a pluralistic landscape where untrained, unqualified and unlicensed informal healthcare providers (IHPs) provide significant share of services. Using qualitative data from 58 interviews in an Indian village, this paper explores how patients choose between IHPs and qualified practitioners in the public and formal private sectors. The study found that patients’ choices were structurally constrained by accessibility and affordability of care and choosing a practitioner from any sector presented some risk. Negotiation and engagement with risks depended on perceived severity of the health condition and trust in practitioners. Patients had low institutional trust in public and formal private sectors, whereas IHPs operated outside any institutional framework. Consequently, people relied on relational or competence-derived interpersonal trust. Care was sought from formal private practitioners for severe issues due to high-competence-based interpersonal trust in them, whereas for other issues IHPs were preferred due to high relationship-based interpersonal trust. The research shows that patients develop a strategic approach to practitioner choice by using trust to negotiate risks, and crucially, in low- and middle-income countries IHPs bridge a gap by providing accessible and affordable care imbued with relational–interpersonal trust

The Structure of the Fusion Glycoprotein of Newcastle Disease Virus Suggests a Novel Paradigm for the Molecular Mechanism of Membrane Fusion

AbstractBackground: Membrane fusion within the Paramyxoviridae family of viruses is mediated by a surface glycoprotein termed the “F”, or fusion, protein. Membrane fusion is assumed to involve a series of structural transitions of F from a metastable (prefusion) state to a highly stable (postfusion) state. No detail is available at the atomic level regarding the metastable form of these proteins or regarding the transitions accompanying fusion.Results: The three-dimensional structure of the fusion protein of Newcastle disease virus (NDV-F) has been determined. The trimeric NDV-F molecule is organized into head, neck, and stalk regions. The head is comprised of a highly twisted β domain and an additional immunoglobulin-like β domain. The neck is formed by the C-terminal extension of the heptad repeat region HR-A, capped by a four-helical bundle. The C terminus of HR-A is encased by a further helix HR-C and a 4-stranded β sheet. The stalk is formed by the remaining visible portion of HR-A and by polypeptide immediately N-terminal to the C-terminal heptad repeat region HR-B. An axial channel extends through the head and neck and is fenestrated by three large radial channels located approximately at the head–neck interface.Conclusion: We propose that prior to fusion activation, the hydrophobic fusion peptides in NDV-F are sequestered within the radial channels within the head, with the central HR-A coiled coil being only partly formed. Fusion activation then involves, inter alia, the assembly of a complete HR-A coiled coil, with the fusion peptides and transmembrane anchors being brought into close proximity. The structure of NDV-F is fundamentally different than that of influenza virus hemagglutinin, in that the central coiled coil is in the opposite orientation with respect to the viral membrane

FMDV replicons encoding green fluorescent protein are replication competent

The study of replication of viruses that require high bio-secure facilities can be accomplished with less stringent containment using non-infectious 'replicon' systems. The FMDV replicon system (pT7rep) reported by Mclnerney et al. (2000) was modified by the replacement of sequences encoding chloramphenicol acetyl-transferase (CAT) with those encoding a functional L proteinase (Lpro) linked to a bi-functional fluorescent/antibiotic resistance fusion protein (green fluorescent protein/puromycin resistance, [GFP-PAC]). Cells were transfected with replicon-derived transcript RNA and GFP fluorescence quantified. Replication of transcript RNAs was readily detected by fluorescence, whilst the signal from replication-incompetent forms of the genome was >2-fold lower. Surprisingly, a form of the replicon lacking the Lpro showed a significantly stronger fluorescence signal, but appeared with slightly delayed kinetics. Replication can, therefore, be quantified simply by live-cell imaging and image analyses, providing a rapid and facile alternative to RT-qPCR or CAT assays

Strengthening the research to policy and practice interface: exploring strategies used by research organisations working on sexual and reproductive health and HIV/AIDS

This commentary introduces the HARPS supplement on getting research into policy and practice in sexual and reproductive health (SRH). The papers in this supplement have been produced by the Sexual Health and HIV Evidence into Practice (SHHEP) collaboration of international research, practitioner and advocacy organizations based in research programmes funded by the UK Department for International Development

Associations of homelessness and residential mobility with length of stay after acute psychiatric admission

Background: A small number of patient-level variables have replicated associations with the length of stay (LOS) of psychiatric inpatients. Although need for housing has often been identified as a cause of delayed discharge, there has been little research into the associations between LOS and homelessness and residential mobility (moving to a new home), or the magnitude of these associations compared to other exposures. Methods: Cross-sectional study of 4885 acute psychiatric admissions to a mental health NHS Trust serving four South London boroughs. Data were taken from a comprehensive repository of anonymised electronic patient records. Analysis was performed using log-linear regression. Results: Residential mobility was associated with a 99% increase in LOS and homelessness with a 45% increase. Schizophrenia, other psychosis, the longest recent admission, residential mobility, and some items on the Health of the Nation Outcome Scales (HoNOS), especially ADL impairment, were also associated with increased LOS. Informal admission, drug and alcohol or other non-psychotic diagnosis and a high HoNOS self-harm score reduced LOS. Including residential mobility in the regression model produced the same increase in the variance explained as including diagnosis; only legal status was a stronger predictor. Conclusions: Homelessness and, especially, residential mobility account for a significant part of variation in LOS despite affecting a minority of psychiatric inpatients; for these people, the effect on LOS is marked. Appropriate policy responses may include attempts to avert the loss of housing in association with admission, efforts to increase housing supply and the speed at which it is made available, and reforms of payment systems to encourage this

Canine babesiosis and tick activity monitored using companion animal electronic health records in the UK

Recent publications highlighting autochthonous Babesia canis infection in dogs from Essex that have not travelled outside the UK are a powerful reminder of the potential for pathogen emergence in new populations. Here the authors use electronic health data collected from two diagnostic laboratories and a network of 392 veterinary premises to describe canine Babesia cases and levels of Babesia concern from January 2015 to March 2016, and the activity of ticks during December 2015–March 2016. In most areas of the UK, Babesia diagnosis in this population was rare and sporadic. In addition, there was a clear focus of Babesia cases in the affected area in Essex. Until February 2016, analysis of health records indicated only sporadic interest in Babesia largely in animals coming from overseas. Following media coverage in March 2016, there was a spike in owner concern that was geographically dispersed beyond the at-risk area. Tick activity (identified as ticks being removed from animals in veterinary consultations) was consistent but low during the period preceding the infections (<5 ticks/10,000 consultations), but increased in March. This highlights the use of electronic health data to describe rapidly evolving risk and concern that follows the emergence of a pathogen