Cortical imbalance following delayed restoration of bilateral hearing in deaf adolescents

Unilateral auditory deprivation in early childhood can lead to cortical strengthening of inputs from the stimulated side, yet the impact of this on bilateral processing when inputs are later restored beyond an early sensitive period is unknown. To address this, we conducted a longitudinal study with 13 bilaterally profoundly deaf adolescents who received unilateral access to sound via a cochlear implant (CI) in their right ear in early childhood before receiving bilateral access to sound a decade later via a second CI in their left ear. Auditory-evoked cortical responses to unilateral and bilateral stimulation were measured repeatedly using electroencephalogram from 1 week to 14 months after activation of their second CI. Early cortical responses from the newly implanted ear and bilateral stimulation were atypically lateralized to the left ipsilateral auditory cortex. Duration of unilateral deafness predicted an unexpectedly stronger representation of inputs from the newly implanted, compared to the first implanted ear, in left auditory cortex. Significant initial reductions in responses were observed, yet a left-hemisphere bias and unequal weighting of inputs favoring the long-term deaf ear did not converge to a balanced state observed in the binaurally developed system. Bilateral response enhancement was significantly reduced in left auditory cortex suggesting deficits in ipsilateral response inhibition of new, dominant, inputs during bilateral processing. These findings paradoxically demonstrate the adaptive capacity of the adolescent auditory system beyond an early sensitive period for bilateral input, as well as restrictions on its potential to fully reverse cortical imbalances driven by long-term unilateral deafness

Effective health care for older people resident in care homes: the optimal study protocol for realist review

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), 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: Care homes in the UK rely on general practice for access to specialist medical and nursing care as well as referral to therapists and secondary care. Service delivery to care homes is highly variable in both quantity and quality. This variability is also evident in the commissioning and organisation of care home-specific services that range from the payment of incentives to general practitioners (GPs) to visit care homes, to the creation of care home specialist teams and outreach services run by geriatricians. No primary studies or systematic reviews have robustly evaluated the impact of these different approaches on organisation and resident-level outcomes. Our aim is to identify factors which may explain the perceived or demonstrated effectiveness of programmes to improve health-related outcomes in older people living in care homes. Methods/Design: A realist review approach will be used to develop a theoretical understanding of what works when, why and in what circumstances. Elements of service models of interest include those that focus on assessment and management of residents’ health, those that use strategies to encourage closer working between visiting health care providers and care home staff, and those that address system-wide issues about access to assessment and treatment. These will include studies on continence, dignity, and speech and language assessment as well as interventions to promote person centred dementia care, improve strength and mobility, and nutrition. The impact of these interventions and their different mechanisms will be considered in relation to five key outcomes: residents’ medication use, use of out of hours’ services, hospital admissions (including use of Accident and Emergency) and length of hospital stay, costs and user satisfaction. An iterative three-stage approach will be undertaken that is stakeholder-driven and optimises the knowledge and networks of the research team. Discussion: This realist review will explore why and for whom different approaches to providing health care to residents in care homes improves access to health care in the five areas of interest. It will inform commissioning decisions and be the basis for further research. This systematic review protocol is registered on the PROSPERO database reference number: CRD42014009112NIHR Health Services & Delivery Research Programme. Project number 11/1021/0

The role of CD73 in the pathogenesis of Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) manifests as a persistent arthropathy, thought to be immune-driven, that when untreated leads to progressive joint destruction. This group of diseases represents an excellent model to investigate immunoregulation because of the possibility to sample cells aspirated from the site of inflammation. This PhD investigated the contribution of defects in purinergic pathways to the pathogenesis of JIA by examining the distribution and enzymatic activity of the ecto-nucleotidase CD73, together with some investigation of expression of CD39 and CD26. The data presented here demonstrate the significantly decreased proportion of CD73+ T and B synovial lymphocytes from JIA patients compared to peripheral blood lymphocytes of both patients and healthy subjects. This reduction increased with higher disease severity (worse in extended compared to persistent oligoarticular JIA patients) and correlated with patient’s cumulative joint count, but not with disease duration. No genetic association for NT5E (encoding CD73) was found that could explain the different levels of CD73 observed within different subtypes of JIA. Treatment with methotrexate, the first line DMARD to control arthritis, did not affect the proportion of CD73+ peripheral blood lymphocytes, nor did this proportion predict response to methotrexate. The reduction of CD73+ synovial lymphocytes and of CD73 protein expression per CD73+ cell was associated with a reduced ability to generate immunoregulatory adenosine in vitro, suggesting low levels of adenosine in the synovium. An incapacity of CD39+ and CD73+ cells to act cooperatively to metabolize ATP to adenosine, further contributes to the impression of low adenosine generation in the JIA joint, and of defective attenuation of inflammation. In vitro, downregulation of CD73+ PBMC and purified CD8+CD73+ T cells was demonstrated upon cell activation. The loss of CD73+ PBMC was associated with a diminished potential to generate adenosine. The loss of CD73+ PBMC appeared to be restricted to proliferating cells. I propose that the CD73 downregulation is associated with defective adenosine levels within the joint, which could contribute to the locally destructive inflammation seen in JIA

Access to recreational physical activities by car and bus : an assessment of socio-spatial inequalities in mainland Scotland

Obesity and other chronic conditions linked with low levels of physical activity (PA) are associated with deprivation. One reason for this could be that it is more difficult for low-income groups to access recreational PA facilities such as swimming pools and sports centres than high-income groups. In this paper, we explore the distribution of access to PA facilities by car and bus across mainland Scotland by income deprivation at datazone level. GIS car and bus networks were created to determine the number of PA facilities accessible within travel times of 10, 20 and 30 minutes. Multilevel negative binomial regression models were then used to investigate the distribution of the number of accessible facilities, adjusting for datazone population size and local authority. Access to PA facilities by car was significantly (p<0.01) higher for the most affluent quintile of area-based income deprivation than for most other quintiles in small towns and all other quintiles in rural areas. Accessibility by bus was significantly lower for the most affluent quintile than for other quintiles in urban areas and small towns, but not in rural areas. Overall, we found that the most disadvantaged groups were those without access to a car and living in the most affluent areas or in rural areas

Relationships, expertise, incentives, and governance: Supporting care home residents' access to health care: An interview study from England

Objectives: To explore what commissioners of care, regulators, providers, and care home residents in England identify as the key mechanisms or components of different service delivery models that support the provision of National Health Service (NHS) provision to independent care homes. Methods: Qualitative, semistructured interviews with a purposive sample of people with direct experience of commissioning, providing, and regulating health care provision in care homes and care home residents. Data from interviews were augmented by a secondary analysis of previous interviews with care home residents on their personal experience of and priorities for access to health care. Analysis was framed by the assumptions of realist evaluation and drew on the constant comparative method to identify key themes about what is required to achieve quality health care provision to care homes and resident health. Results: Participants identified 3 overlapping approaches to the provision of NHS that they believed supported access to health care for older people in care homes: (1) Investment in relational working that fostered continuity and shared learning between visiting NHS staff and care home staff, (2) the provision of age-appropriate clinical services, and (3) governance arrangements that used contractual and financial incentives to specify a minimum service that care homes should receive. Conclusion: The 3 approaches, and how they were typified as working, provide a rich picture of the stakeholder perspectives and the underlying assumptions about how service delivery models should work with care homes. The findings inform how evidence on effective working in care homes will be interrogated to identify how different approaches, or specifically key elements of those approaches, achieve different health-related outcomes in different situations for residents and associated health and social care organizations.Open Access funded by Department of Health UK

The Higgs boson in the MSSM in light of the LHC

We investigate the expectations for the light Higgs signal in the MSSM in different search channels at the LHC. After taking into account dark matter and flavor constraints in the MSSM with eleven free parameters, we show that the light Higgs signal in the $gamma\gamma$ channel is expected to be at most at the level of the SM Higgs, while the $h\rightarrow b\bar{b}$ from W fusion and/or the $h \rightarrow\tau\bar\tau$ can be enhanced. For the main discovery mode, we show that a strong suppression of the signal occurs in two different cases: low $M_A$ or large invisible width. A more modest suppression is associated with the effect of light supersymmetric particles. Looking for such modification of the Higgs properties and searching for supersymmetric partners and pseudoscalar Higgs offer two complementary probes of supersymmetry.Comment: 19 pages, 8 figure

Low CD73 expression on synovial lymphocytes correlates with reduced adenosine generation and higher disease severity in juvenile idiopathic arthritis

Objective To investigate the expression and the adenosine-generating activity of the ecto-5'-nucleotidase CD73 on synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) from children with arthritis. Methods Given the role of CD73 protein in the production of anti-inflammatory adenosine which intersects with inflammatory biology, its expression on lymphocytes was determined by flow cytometry. The CD73 AMPase activity of PBMC and SFMC was measured by HPLC. The effects of cell activation on CD73 expression were examined by in vitro culture of PBMC. Results CD8+ and CD19+ synovial lymphocytes from patients with juvenile idiopathic arthritis (JIA) expressed decreased levels of CD73 compared to both paired JIA PBMC and those from healthy controls. When comparing percentages of CD73+ synovial fluid lymphocytes in the two clinical forms of oligoarthritis, those with extended oligoarthritis showed lower CD73 expression compared to patients with the milder form of disease. Synovial CD8+ T cells had a lower ability to produce adenosine from Etheno-AMP compared to CD8+ PBMC. T cell activation through the TCR of CD8+CD73+ cells and B cell activation through TLR9 resulted in reduced expression of CD73. This downregulation occurred on dividing cells. Conclusion These data show that low CD73 expression on T and B cells in the inflammatory site is related to cell proliferation and is correlated with the clinical severity of oligoarticular JIA. The decreased CD73 expression on SFMC in turn results in reduced adenosine production, which would lead to decreased potential for anti-inflammatory activity

Palmar-divergent dislocation of the scaphoid and the lunate

We describe a patient with palmar-divergent dislocation of the scaphoid and lunate. After successful closed reduction, the scapholunate and lunotriquetral ligaments were sutured through the dorsal approach, and the anterior capsule was sutured through the palmar approach. The scapholunate and lunotriquetral joints were fixed with Kirschner wires for 7 weeks. At the 1-year follow-up, magnetic resonance imaging showed no evidence of avascular necrosis of the scaphoid or lunate, and radiographs showed no evidence of the dorsal and volar intercalated segment instability patterns associated with carpal instability. However, flexion of the scaphoid and a break in Gilula’s line remained. To our knowledge, this is the first report showing treatment of palmar-divergent dislocation of the scaphoid and lunate by suturing the carpal interosseous ligaments

Re-Assembly of the Genome of Francisella tularensis Subsp. holarctica OSU18

Francisella tularensis is a highly infectious human intracellular pathogen that is the causative agent of tularemia. It occurs in several major subtypes, including the live vaccine strain holarctica (type B). F. tularensis is classified as category A biodefense agent in part because a relatively small number of organisms can cause severe illness. Three complete genomes of subspecies holarctica have been sequenced and deposited in public archives, of which OSU18 was the first and the only strain for which a scientific publication has appeared [1]. We re-assembled the OSU18 strain using both de novo and comparative assembly techniques, and found that the published sequence has two large inversion mis-assemblies. We generated a corrected assembly of the entire genome along with detailed information on the placement of individual reads within the assembly. This assembly will provide a more accurate basis for future comparative studies of this pathogen