Bottom-Up versus Top-Down Induction of Sleep by Zolpidem Acting on Histaminergic and Neocortex Neurons

Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase sleep time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases the EEG power, an effect that depends on α1 subunit-containing receptors, and which may make zolpidem-induced sleep less optimal. In this paper, we investigate whether zolpidem needs to potentiate only particular GABAergic pathways to induce sleep without reducing EEG power. Mice with a knock-in F77I mutation in the GABAA receptor γ2 subunit gene are zolpidem-insensitive. Using these mice, GABAA receptors in the frontal motor neocortex and hypothalamic (tuberomammillary nucleus) histaminergic-neurons of γ2I77 mice were made selectively sensitive to zolpidem by genetically swapping the γ2I77 subunits with γ2F77 subunits. When histamine neurons were made selectively zolpidem-sensitive, systemic administration of zolpidem shortened sleep latency and increased sleep time. But in contrast to the effect of zolpidem on wild-type mice, the power in the EEG spectra of NREM sleep was not decreased, suggesting that these EEG power-reducing effects of zolpidem do not depend on reduced histamine release. Selective potentiation of GABAA receptors in the frontal cortex by systemic zolpidem administration also reduced sleep latency, but less so than for histamine neurons. These results could help with the design of new sedatives that induce a more natural sleep

A reassuring presence: An evaluation of Bradford District Hospice at Home service

Within the United Kingdom, a developing role for primary care services in cancer and palliative care has resulted in an increase in palliative home care teams. The provision of professional care in the home setting seeks to provide necessary services and enhanced choice for patients whose preference is to die at home. A mismatch between patient preference for home death and the actual number of people who died at home was identified within Bradford, the locality of this study. In response to this mismatch, and reflecting the policy environment of wishing to enhance community service provision, the four Primary Care Trusts (PCTs) in the city sought to offer support to patients who wished to remain in their own homes through the final stages of a terminal illness. To offer this support they set up a dedicated hospice at home team. This would provide services and support for patients in achieving a dignified, symptom free and peaceful death, allowing families to maximise time spent together. The aim of the study was to evaluate the Bradford hospice at home service from the perspective of carers, nurses and General Practitioners. Postal questionnaires were sent to carers (n = 289), district nurses (n = 508) and GP's (n = 444) using Bradford's hospice at home service. Resulting quantitative data was analysed using the Statical Package for Social Sciences (SPSS) and qualitative data was analysed using grounded theory techniques. The data from carers, district nurses and GPs provide general support for the Bradford hospice at home service. Carers valued highly the opportunity to 'fulfil a promise' to the individual who wished to be cared for at home. District nurses and GPs cited the positive impact of access to specialist expertise. This was a 'reassuring presence' for primary healthcare teams and offered 'relief of carer anxiety' by providing prompt, accessible and sensitive care. Carers and health professionals welcomed the increased possibility of patients being cared for at home. The study identified the need to focus on improving skill levels of staff and on ensuring continuity of care

RRS James Cook Cruise JC191 19 January - 1 March 2020 Hydrographic sections from the Florida Straits to the Canaries Current across 24ºN in the Atlantic Ocean

A hydrographic section across the North Atlantic Ocean at a nominal latitude of 24°N was occupied by the RRS James Cook (cruise identifier: JC191) from 19 January to 1 March, 2020. The ship departed from Port Everglades, USA, completing a total of 135 CTD stations over the Florida Straits, the western basin, Mid-Atlantic Ridge, eastern basin and eastern boundary up to Morocco, before ending the cruise in Santa Cruz de Tenerife, Spain. The main objectives of the JC191 research expedition was to collect/measure physical-, chemical-, and biological-ocean data with the purpose of estimating heat, freshwater and carbon budgets on low frequency time scales. All CTD stations had measurements from a CTD rosette equipped with temperature, conductivity, pressure, oxygen sensors, in addition to water captured from 24 niskin bottles fired at varying intervals throughout the full depth water column. The water from the niskin bottles was analysed for dissolved oxygen, carbon (DIC/TA), nutrients, and conductivity. Water for methane (CH4), C14, C13, and pigments (filtered) was collected for onshore analysis. The CTD rosette was also equipped with 2 RBR loggers measuring conductivity, temperature and pressure (up to 6,000m), and a lowered Acoustic Doppler Current Profiler (LADCP) making full depth velocity measurements. The 135 CTD stations include 2 carbon blank stations, and 2 bulk water stations for incubations. In addition to the CTD stations, the RRS James Cook has an underway system, which includes an intake for surface water to be pumped into the water bottle annex and the deck lab; two vessel mounted ADCPs (VMADCPs). A thermosalinograph and a fluorometer, installed in the water bottle annex, continually recorded conductivity, temperature and fluorescence. Water from the CTD was collected to calibrate the ship’s underway TSG. The VMADCPs, 75Hz and 150HZ, mounted on the drop keel record ocean velocities in roughly the top 300- and 600-m, respectively. Surface carbon and methane measurements were also recorded from the underway systems, and surface meteorological variables were monitored via the meteorological sampling system and the pumped water underway system. Finally bathymetric data were recorded an EA640 echosounder and a Kongsberg EM122 multibeam, both of which are mounted on the ship’s hull. Last, 5 Deep Apex Argo floats measuring conductivity, temperature, pressure and oxygen (except for one float not equipped with an optode) were deployed in the western basin. Many of the science party also engaged in extensive outreach via blogs and social media, heightening visibility of the science teams activities to the oceanographic community and the general public. This report summarises the data collected and analysed, and the methodology used for the acquisition and processing of the data onboard the James Cook during the JC191 research expedition

Constitutivism

A brief explanation and overview of constitutivism

Measuring the effect of intimate partner violence on health-related quality of life: a qualitative focus group study

Abstract Background Health related quality of life (HRQOL) can be measured by a wide range of instruments, many of which have been designed for specific conditions or uses. Preference-based measures assess the value individuals place on health, and are included in economic evaluations of treatments and interventions (such as cost effectiveness analysis). As economic evaluation becomes more common, it is important to assess the applicability of preference-based health related quality of life (HRQOL) measures to public health issues. This study investigated the usefulness of such instruments in the context of intimate partner violence (IPV), a public health concern that that can seriously affect quality of life. Methods The study consisted of focus groups with abused women to determine the aspects of life affected by IPV, and an analysis of existing HRQOL measures. Eight focus groups (n = 40) were conducted in which participants discussed the domains of health affected by IPV. Results were content analyzed and compared with the domains of health included in four commonly-used, preference-based HRQOL measures. Results The average focus group participant was 43 years old, unemployed, African American, with 3 children. Domains of health reported to be affected by IPV included physical functioning, emotional and psychological functioning, social functioning and children\u27s functioning. Psychological health was the most severely affected domain. The Short Form 36, the Health Utilities Index, the EuroQol 5D, and the Quality of Well-being Scale were found to vary in the degree to which they include domains of health important in IPV. Psychological health is included to a limited extent, and the spill-over effect of a condition on other family members, including children, is not included at all. Conclusion Emotional and psychological health plays an important role in the overall HRQOL of abused women but is relatively underemphasized in preference-based HRQOL measures. This may lead to an underestimation of the impact of partner violence on HRQOL when using these measures and in economic evaluations that rely thereon. Holistic measurement approaches or expanded measures that capture the far-reaching effects of IPV on HRQOL may be needed to accurately measure the effect of this condition on women\u27s health

A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses

Many contemporary studies have shown that astrocytes play a significant role in modulating both short and long form of synaptic plasticity. There are very few experimental models which elucidate the role of astrocyte over Long-term Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of astrocytes in induction of LTP at single hippocampal synapses. They suggested a purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic induction were not investigated. Here, in this article, we propose a mathematical model for astrocyte modulated LTP which successfully emulates the experimental findings of Perea & Araque (2007). Our study suggests the role of retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to appear

Current state of fine mineral tailings treatment: A critical review on theory and practice

The mining industry produces fluid fine mineral tailings on the order of millions of tonnes each year, with billions of tonnes already stored globally. This trend is expected to escalate as demand for mineral products continues to grow with increasingly lower grade ores being more commonly exploited by hydrometallurgy. Ubiquitous presence and enrichment of fine solids such as silt and clays in fluid fine mineral tailings prevent efficient solid-liquid separation and timely re-use of valuable process water. Long-term storage of such fluid waste materials not only incurs a huge operating cost, but also creates substantial environmental liabilities of tailings ponds for mining operators. This review broadly examines current theoretical understandings and prevalent industrial practices on treating fine mineral tailings for greater water recovery and reduced environmental footprint of mining operations

A review of source tracking techniques for fine sediment within a catchment

Excessive transport of fine sediment, and its associated pollutants, can cause detrimental impacts in aquatic environments. It is therefore important to perform accurate sediment source apportionment to identify hot spots of soil erosion. Various tracers have been adopted, often in combination, to identify sediment source type and its spatial origin; these include fallout radionuclides, geochemical tracers, mineral magnetic properties and bulk and compound-specific stable isotopes. In this review, the applicability of these techniques to particular settings and their advantages and limitations are reviewed. By synthesizing existing approaches, that make use of multiple tracers in combination with measured changes of channel geomorphological attributes, an integrated analysis of tracer profiles in deposited sediments in lakes and reservoirs can be made. Through a multi-scale approach for fine sediment tracking, temporal changes in soil erosion and sediment load can be reconstructed and the consequences of changing catchment practices evaluated. We recommend that long-term, as well as short-term, monitoring of riverine fine sediment and corresponding surface and subsurface sources at nested sites within a catchment are essential. Such monitoring will inform the development and validation of models for predicting dynamics of fine sediment transport as a function of hydro-climatic and geomorphological controls. We highlight that the need for monitoring is particularly important for hilly catchments with complex and changing land use. We recommend that research should be prioritized for sloping farmland-dominated catchments