3,314 research outputs found
Group-Based Parent Training Interventions for Parents of Children with Autism Spectrum Disorders: a Literature Review
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Parents of children with autism spectrum disorders should have access to interventions to help them understand and support their child. This literature review examines the existing evidence for group-based parent training interventions that support parents of children with autism. From the literature, core intervention processes and outcomes are identified and include parenting and parent behaviour, parent health, child behaviour and peer and social support. Results show a positive trend for intervention effectiveness, but findings are limited by low-quality studies and heterogeneity of intervention content, outcomes and outcome measurement. Future research should focus on specifying effective intervention ingredients and modes of delivery, consistent and reliable outcome measurement, and improving methodological rigour to build a more robust evidence base
Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.
Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints
Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach
This article is available through the Brunel Open Access Publishing Fund. Copyright 2014 Rogers et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants. Methods: Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation. Results: Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration. Conclusion: Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.The National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0909-20055)
Big data and data repurposing – using existing data to answer new questions in vascular dementia research
Introduction: 
Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD.
Methods: 
We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015).
Results: 
We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach.
Conclusions: 
There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use
Pulsar Results with the Fermi Large Area Telescope
The launch of the Fermi Gamma-ray Space Telescope has heralded a new era in
the study of gamma-ray pulsars. The population of confirmed gamma-ray pulsars
has gone from 6-7 to more than 60, and the superb sensitivity of the Large Area
Telescope (LAT) on Fermi has allowed the detailed study of their spectra and
light curves. Twenty-four of these pulsars were discovered in blind searches of
the gamma-ray data, and twenty-one of these are, at present, radio quiet,
despite deep radio follow-up observations. In addition, millisecond pulsars
have been confirmed as a class of gamma-ray emitters, both individually and
collectively in globular clusters. Recently, radio searches in the direction of
LAT sources with no likely counterparts have been highly productive, leading to
the discovery of a large number of new millisecond pulsars. Taken together,
these discoveries promise a great improvement in the understanding of the
gamma-ray emission properties and Galactic population of pulsars. We summarize
some of the results stemming from these newly-detected pulsars and their timing
and multi-wavelength follow-up observations.Comment: 21 pages, 9 figures, to appear in Proceedings of ICREA Workshop on
  The High-Energy Emission from Pulsars and their Systems, Sant Cugat, Spain,
  2010 April 12-16 (Springer
Ethanol reversal of tolerance to the respiratory depressant effects of morphine
Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths
UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets
Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research
Programme (Grant Reference Number RP-PG-0310-1004)
Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes
Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans
Thermodynamics of Holographic Defects
Using the AdS/CFT correspondence, we study the thermodynamic properties and
the phase diagram of matter fields on (2+1)-dimensional defects coupled to a
(3+1)-dimensional N=4 SYM "heat bath". Considering a background magnetic field,
(net) quark density, defect "magnitude"  and the mass of the
matter, we study the defect contribution to the thermodynamic potentials and
their first and second derivatives to map the phases and study their physical
properties.
  We find some features that are qualitatively similar to other systems e.g. in
(3+1) dimensions and a number of features that are particular to the defect
nature, such as its magnetic properties, unexpected properties at T->0 and
finite density; and the finite  effects, e.g. a diverging
susceptibility and vanishing density of states at small temperatures, a
physically consistent negative heat capacity and new types of consistent
phases.Comment: 33 pages, 16 figures (jpg and pdf), typos fixed and references added,
  final version published in JHE
Prime movers : mechanochemistry of mitotic kinesins
Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation
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