442 research outputs found
Assessment of cognitive safety in clinical drug development
Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks
Self-adaptive quantum particle swarm optimization for dynamic environments
The quantum-inspired particle swarm optimization (QPSO) algorithm has been developed to find and track an optimum for dynamic optimization problems. Though QPSO has been shown to be effective, despite its simplicity, it does introduce an additional control parameter: the radius of the quantum cloud. The performance of QPSO is sensitive to the value assigned to this problem dependent parameter, which basically limits the area of the search space wherein new, better optima can be detected. This paper proposes a strategy to dynamically adapt the quantum radius, with changes in the environment. A comparison of the adaptive radius QPSO with the static radius QPSO showed that the adaptive approach achieves desirable results, without prior tuning of the quantum radius.http://link.springer.combookseries/5582019-10-03hj2018Computer Scienc
The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial
Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015
Understanding the small object argument
The small object argument is a transfinite construction which, starting from
a set of maps in a category, generates a weak factorisation system on that
category. As useful as it is, the small object argument has some problematic
aspects: it possesses no universal property; it does not converge; and it does
not seem to be related to other transfinite constructions occurring in
categorical algebra. In this paper, we give an "algebraic" refinement of the
small object argument, cast in terms of Grandis and Tholen's natural weak
factorisation systems, which rectifies each of these three deficiencies.Comment: 42 pages; supersedes the earlier arXiv preprint math/0702290; v2:
final journal version, minor corrections onl
The North Wyke Farm Platform: effect of temperate grassland farming systems on soil moisture contents, runoff and associated water quality dynamics
This is the final version of the article. Available from Wiley via the DOI in this record.The North Wyke Farm Platform was established as a United Kingdom national capability for collaborative research, training and knowledge exchange in agro-environmental sciences. Its remit is to research agricultural productivity and ecosystem responses to different management practices for beef and sheep production in lowland grasslands. A system based on permanent pasture was implemented on three 21-ha farmlets to obtain baseline data on hydrology, nutrient cycling and productivity for 2 years. Since then two farmlets have been modified by either (i) planned reseeding with grasses that have been bred for enhanced sugar content or deep-rooting traits or (ii) sowing grass and legume mixtures to reduce nitrogen fertilizer inputs. The quantities of nutrients that enter, cycle within and leave the farmlets were evaluated with data recorded from sensor technologies coupled with more traditional field study methods. We demonstrate the potential of the farm platform approach with a case study in which we investigate the effects of the weather, field topography and farm management activity on surface runoff and associated pollutant or nutrient loss from soil. We have the opportunity to do a full nutrient cycling analysis, taking account of nutrient transformations in soil, and flows to water and losses to air. The NWFP monitoring system is unique in both scale and scope for a managed land-based capability that brings together several technologies that allow the effect of temperate grassland farming systems on soil moisture levels, runoff and associated water quality dynamics to be studied in detail. HIGHLIGHTS: Can meat production systems be developed that are productive yet minimize losses to the environment?The data are from an intensively instrumented capability, which is globally unique and topical.We use sensing technologies and surveys to show the effect of pasture renewal on nutrient losses.Platforms provide evidence of the effect of meteorology, topography and farm activity on nutrient loss.The North Wyke Farm Platform is a UK National Capability supported by the Biotechnology and Biological Sciences Research Council (BBSRC BB/J004308/1)
Evaluating a selective prevention programme for binge drinking among young adolescents: study protocol of a randomized controlled trial
Contains fulltext :
99319.pdf (publisher's version ) (Open Access)Background
In comparison to other Europe countries, Dutch adolescents are at the top in drinking frequency and binge drinking. A total of 75% of the Dutch 12 to 16 year olds who drink alcohol also engage in binge drinking. A prevention programme called Preventure was developed in Canada to prevent adolescents from binge drinking. This article describes a study that aims to assess the effects of this selective school-based prevention programme in the Netherlands.
Methods
A randomized controlled trial is being conducted among 13 to 15-year-old adolescents in secondary schools. Schools were randomly assigned to the intervention and control conditions. The intervention condition consisted of two 90 minute group sessions, carried out at the participants' schools and provided by a qualified counsellor and a co-facilitator. The intervention targeted young adolescents who demonstrated personality risk for alcohol abuse. The group sessions were adapted to four personality profiles. The control condition received no further intervention above the standard substance use education sessions provided in the Dutch national curriculum. The primary outcomes will be the percentage reduction in binge drinking, weekly drinking and drinking-related problems after three specified time periods. A screening survey collected data by means of an Internet questionnaire. Students have completed, or will complete, a post-treatment survey after 2, 6, and 12 months, also by means of an online questionnaire.
Discussion
This study protocol presents the design and current implementation of a randomized controlled trial to evaluate the effectiveness of a selective alcohol prevention programme. We expect that a significantly lower number of adolescents will binge drink, drink weekly, and have drinking-related problems in the intervention condition compared to the control condition, as a result of this intervention.9 p
Mixed reality simulation of rasping procedure in artificial cervical disc replacement (ACDR) surgery
<p>Abstract</p> <p>Background</p> <p>Until quite recently spinal disorder problems in the U.S. have been operated by fusing cervical vertebrae instead of replacement of the cervical disc with an artificial disc. Cervical disc replacement is a recently approved procedure in the U.S. It is one of the most challenging surgical procedures in the medical field due to the deficiencies in available diagnostic tools and insufficient number of surgical practices For physicians and surgical instrument developers, it is critical to understand how to successfully deploy the new artificial disc replacement systems. Without proper understanding and practice of the deployment procedure, it is possible to injure the vertebral body. Mixed reality (MR) and virtual reality (VR) surgical simulators are becoming an indispensable part of physicians’ training, since they offer a risk free training environment. In this study, MR simulation framework and intricacies involved in the development of a MR simulator for the rasping procedure in artificial cervical disc replacement (ACDR) surgery are investigated. The major components that make up the MR surgical simulator with motion tracking system are addressed. </p> <p>Findings</p> <p>A mixed reality surgical simulator that targets rasping procedure in the artificial cervical disc replacement surgery with a VICON motion tracking system was developed. There were several challenges in the development of MR surgical simulator. First, the assembly of different hardware components for surgical simulation development that involves knowledge and application of interdisciplinary fields such as signal processing, computer vision and graphics, along with the design and placements of sensors etc . Second challenge was the creation of a physically correct model of the rasping procedure in order to attain critical forces. This challenge was handled with finite element modeling. The third challenge was minimization of error in mapping movements of an actor in real model to a virtual model in a process called registration. This issue was overcome by a two-way (virtual object to real domain and real domain to virtual object) semi-automatic registration method.</p> <p>Conclusions</p> <p>The applicability of the VICON MR setting for the ACDR surgical simulator is demonstrated. The main stream problems encountered in MR surgical simulator development are addressed. First, an effective environment for MR surgical development is constructed. Second, the strain and the stress intensities and critical forces are simulated under the various rasp instrument loadings with impacts that are applied on intervertebral surfaces of the anterior vertebrae throughout the rasping procedure. Third, two approaches are introduced to solve the registration problem in MR setting. Results show that our system creates an effective environment for surgical simulation development and solves tedious and time-consuming registration problems caused by misalignments. Further, the MR ACDR surgery simulator was tested by 5 different physicians who found that the MR simulator is effective enough to teach the anatomical details of cervical discs and to grasp the basics of the ACDR surgery and rasping procedure</p
Roles of instrumented farm-scale trials in trade-off assessments of pasture-based ruminant production systems
For livestock production systems to play a positive role in global food security, the balance between their benefits and disbenefits to society must be appropriately managed. Based on the evidence provided by field-scale randomised controlled trials around the world, this debate has traditionally centred on the concept of economic-environmental trade-offs, of which existence is theoretically assured when resource allocation is perfect on the farm. Recent research conducted on commercial farms indicates, however, that the economic-environmental nexus is not nearly as straightforward in the real world, with environmental performances of enterprises often positively correlated with their economic profitability. Using high-resolution primary data from the North Wyke Farm Platform, an intensively instrumented farm-scale ruminant research facility located in southwest United Kingdom, this paper proposes a novel, information-driven approach to carry out comprehensive assessments of economic-environmental trade-offs inherent within pasture-based cattle and sheep production systems. The results of a data-mining exercise suggest that a potentially systematic interaction exists between 'soil health', ecological surroundings and livestock grazing, whereby a higher level of soil organic carbon (SOC) stock is associated with a better animal performance and less nutrient losses into watercourses, and a higher stocking density with greater botanical diversity and elevated SOC. We contend that a combination of farming system-wide trials and environmental instrumentation provides an ideal setting for enrolling scientifically sound and biologically informative metrics for agricultural sustainability, through which agricultural producers could obtain guidance to manage soils, water, pasture and livestock in an economically and environmentally acceptable manner. Priority areas for future farm-scale research to ensure long-term sustainability are also discussed
Connectivity and systemic resilience of the Great Barrier Reef
Australia’s iconic Great Barrier Reef (GBR) continues to suffer from repeated impacts of cyclones, coral bleaching, and outbreaks of the coral-eating crown-of-thorns starfish (COTS), losing much of its coral cover in the process. This raises the question of the ecosystem’s systemic resilience and its ability to rebound after large-scale population loss. Here, we reveal that around 100 reefs of the GBR, or around 3%, have the ideal properties to facilitate recovery of disturbed areas, thereby imparting a level of systemic resilience and aiding its continued recovery. These reefs (1) are highly connected by ocean currents to the wider reef network, (2) have a relatively low risk of exposure to disturbances so that they are likely to provide replenishment when other reefs are depleted, and (3) have an ability to promote recovery of desirable species but are unlikely to either experience or spread COTS outbreaks. The great replenishment potential of these ‘robust source reefs’, which may supply 47% of the ecosystem in a single dispersal event, emerges from the interaction between oceanographic conditions and geographic location, a process that is likely to be repeated in other reef systems. Such natural resilience of reef systems will become increasingly important as the frequency of disturbances accelerates under climate change
Improving Hospital at Home for frail older people: insights from a quality improvement project to achieve change across regional health and social care sectors.
Against a background of rising numbers of frail older people, there is a need to improve quality and safety of services whilst containing costs. Improving patient outcomes requires change across hospital and community systems. Our objective was to change practice in order to deliver a Hospital at Home programme (admission avoidance and early supported discharge) for frail older people across a regional commissioning area. The programme, undertaken within the Northern, Eastern & Western Devon Clinical Commissioning Group (CCG) sub-localities of Exeter (population 120,000) and Woodbury, Exmouth and Budleigh Salterton (towns with populations of around 10,000), involved reconfiguration of existing services rather than being a stand-alone intervention.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.Publishe
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