721 research outputs found

    Factors affecting decisions to extend access to primary care: results of a qualitative evaluation of general practitioners' views

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    OBJECTIVES: To report general practitioners' (GPs') views and experiences of an Enhanced Primary Care programme (EPCP) funded as part of the Prime Minister's Challenge Fund (second wave) for England which aimed to extend patient access to primary care. SETTING: Primary care in Sheffield, England. PARTICIPANTS: Semi-structured interviews with a purposive sample of GPs working in 24 practices across the city. RESULTS: Four core themes were derived: GPs' receptivity to the aims of the EPCP, their capacity to support integrated care teams, their capacity to manage urgent care and the value of some new community-based schemes to enhance locality-based primary care. GPs were aware of the policy initiatives associated with out-of-hours access that aimed to reduce emergency department and hospital admissions. Due to limited capacity to respond to the programme, they selected elements that directly related to local patient demand and did not increase their own workload. CONCLUSIONS: The variation in practice engagement and capacity to manage changes in primary care services warrants a subtle and specialist approach to programme planning. The study makes the case for enhanced planning and organisational development with GPs as stakeholders within individual practices and groups. This would ensure that policy implementation is effective and sustained at local level. A failure to localise implementation may be associated with increased workloading in primary care without the sustained benefits to patients and the public. To enable GPs to become involved in systems transformation, further research is needed to identify the best methods to engage GPs in programme planning and evaluation

    Pregnancies in older women living with HIV in the UK and Ireland.

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    OBJECTIVES: The aim of the study was to compare maternal characteristics and pregnancy outcomes in women aged < 40 years and ≥ 40 years in a large unselected population of HIV-positive women delivering in the UK and Ireland between 2000 and 2014. METHODS: Comprehensive population-based surveillance data on all HIV-positive pregnant women and their children seen for care in the UK and Ireland are collected through the National Study of HIV in Pregnancy and Childhood. All singleton and multiple pregnancies reported by the end of June 2015 resulting in live birth or stillbirth to women diagnosed with HIV infection before delivery and delivering in 2000-2014 were included. Logistic regression models were fitted in analyses examining the association between older maternal age and specific outcomes (preterm delivery and stillbirth). RESULTS: Among 15 501 pregnancies in HIV-positive women, the proportion in older women (≥ 40 years) increased from 2.1% (73 of 3419) in 2000-2004 to 8.9% (510 of 5748) in 2010-2014 (P < 0.001). Compared with pregnancies in younger women, those in older women were more likely to result in multiple birth (3.0 vs. 1.9% in younger women; P = 0.03), stillbirth (adjusted odds ratio 2.39; P = 0.004) or an infant with a chromosomal abnormality (1.6 vs. 0.2%, respectively; P < 0.001). However, there was no increased risk of preterm delivery, low birth weight or mother-to-child HIV transmission among older mothers. CONCLUSIONS: There has been a significant increase over time in the proportion of deliveries to women living with HIV aged ≥ 40 years, which has implications for pregnancy management, given their increased risk of multiple births, stillbirth and chromosomal anomalies, as also apparent in the general population

    Towards a first-principles theory of surface thermodynamics and kinetics

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    Understanding of the complex behavior of particles at surfaces requires detailed knowledge of both macroscopic and microscopic processes that take place; also certain processes depend critically on temperature and gas pressure. To link these processes we combine state-of-the-art microscopic, and macroscopic phenomenological, theories. We apply our theory to the O/Ru(0001) system and calculate thermal desorption spectra, heat of adsorption, and the surface phase diagram. The agreement with experiment provides validity for our approach which thus identifies the way for a predictive simulation of surface thermodynamics and kinetics.Comment: 4 pages including 3 figures. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

    Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

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    Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

    Mitigating bias blind spot via a serious video game

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    We employed a serious video game to train participants on bias blind spot (BBS), capturing training effects on BBS mitigation and knowledge at three points in time. Experiment 1 (N = 703) compared the effects of hybrid training (a combination of implicit and explicit training) to implicit training; Experiment 2 (N = 620) tested the effects of just-in-time versus delayed feedback; and Experiment 3 (N = 626) examined the effects of singleplayer versus multiplayer learning environments. We also tested differences in game duration (30 vs. 60 minute play) and repetition (single vs. repeated play). Overall, the video game decreased BBS linearly over time and increased BBS knowledge at posttest, but knowledge decayed at 8-week posttest. These and other results are discussed, along with the implications, limitations, and future research directions

    Dantrolene as a treatment option for RYR1-related rhabdomyolysis

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    Characterization of Electronic Transport through Amorphous TiO_2 Produced by Atomic-Layer Deposition

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    Electrical transport in amorphous titanium dioxide (a-TiO_2) thin films, deposited by atomic layer deposition (ALD), and across heterojunctions of p+-Si|a-TiO_2|metal substrates that had various top metal contacts has been characterized by ac conductivity, temperature-dependent dc conductivity, space-charge-limited current spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, X-ray photoelectron spectroscopy, and current density versus voltage (J–V) characteristics. Amorphous TiO_2 films were fabricated using either tetrakis(dimethylamido)-titanium with a substrate temperature of 150 °C or TiCl_4 with a substrate temperature of 50, 100, or 150 °C. EPR spectroscopy of the films showed that the Ti^(3+) concentration varied with the deposition conditions and increases in the concentration of Ti^(3+) in the films correlated with increases in film conductivity. Valence band spectra for the a-TiO_2 films exhibited a defect-state peak below the conduction band minimum (CBM) and increases in the intensity of this peak correlated with increases in the Ti^(3+) concentration measured by EPR as well as with increases in film conductivity. The temperature-dependent conduction data showed Arrhenius behavior at room temperature with an activation energy that decreased with decreasing temperature, suggesting that conduction did not occur primarily through either the valence or conduction bands. The data from all of the measurements are consistent with a Ti^(3+) defect-mediated transport mode involving a hopping mechanism with a defect density of 10^(19) cm^(–3), a 0.83 wide defect band centered 1.47 eV below the CBM, and a free-electron concentration of 10^(16) cm^(–3). The data are consistent with substantial room-temperature anodic conductivity resulting from the introduction of defect states during the ALD fabrication process as opposed to charge transport intrinsically associated with the conduction band of TiO_2

    Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

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    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
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