Thames Valley Hospital

Josephson junctions manufactured to tight tolerances are necessary components for superconducting quantum computing. Developing precise manufacturing techniques for Josephson junctions requires an understanding of their make-up and robust feedback metrics against which to optimize. Here, we consider complementary techniques and assess what conclusions they allow us to draw about the barriers in junctions. Monte Carlo simulations of barriers show that standard deviations of 15–20% of the total barrier thickness are compatible with our experimental data. Electrical breakdown allows us to probe the weakest points in barriers. Narrowing the distribution of this breakdown provides a promising feedback mechanism for barrier optimisation. Grouping junctions by breakdown voltage allows us to identify sub-ensembles of junctions with different median resistance. Transmission electron microscopy can be used to find average barrier thickness, although we highlight challenges in forming robust conclusions on the distribution of thicknesses in a barrier from these experiments.

Abstract Study question Does high-dose testosterone therapy affect the stage distribution, morphological health and DNA damage repair capacity of human ovarian follicles and their survival in vitro? Summary answer Testosterone exposure is associated with reduced follicle growth activation, reduced follicle health and increased DNA damage: these further deteriorate after six days of culture. What is known already Androgens have diverse actions within the ovary, however, there is a lack of information regarding the long-term effects of high-dose testosterone on ovarian function and reproductive potential. Cumulus-oocyte complexes recovered from transgender men have been successfully matured in-vitro but little is known regarding the impact of this gender affirming endocrine therapy on the primordial follicle pool Study design, size, duration Whole ovaries were obtained from four transgender men aged 25-36 years with informed consent at oophorectomy. All patients had received 1000mg testosterone undecanoate intramuscularly at 12-16 week intervals for a minimum of 4 years pre-operatively. Cortical tissues were dissected into small pieces (≈1x1x0.5mm) and either immediately fixed for histological analysis or cultured for 6 days. Testosterone-treated ovaries were compared to cortical biopsies from age-matched healthy women obtained at caesarean section (n = 4, age 26-36). Participants/materials, setting, methods Follicle number, classification of developmental stage and morphology were evaluated by histological analysis of ovarian cortical tissue from day 0 and 6 days post culture. Immunohistochemical analysis included γH2AX as a marker of DNA damage, and meiotic recombination 11 (MRE11), ataxia telangiectasia mutated (ATM) and Rad51 as DNA repair proteins. A total of 3802 follicles from testosterone exposed and 878 from control ovaries were analysed. Main results and the role of chance At day 0 (D0), transgender tissue had a higher proportion of non-growing follicles (92.7±1.7%) compared to control (85.4±6.2%, p < 0.05) but a lower proportion of morphologically healthy follicles (non-growing 59%, primary 61%, secondary 36%; vs 83%, 75%, 80% in controls, all p < 0.005). After 6 days in culture, the proportion of growing follicles increased (51.3% vs 46.5%) but follicle health further declined (all stages p < 0.005). DNA damage was assessed by expression of γH2AX. At D0, the proportion of oocytes showing DNA damage was significantly higher in transgender non-growing follicles (48.1±12.5%, vs 12.3±0.25%, p < 0.005). After culture, γH2AX expression increased in both transgender (p < 0.005) and controls (p < 0.005) but remained higher in transgender oocytes (non-growing 72.2%, primary 71.7% vs 27.3%, 46.2%, all p < 0.05). At D0, there was no difference in expression of DNA repair enzymes ATM and RAD51 between transgender and control oocytes, and increased expression of MRE11 in control non-growing follicles (p < 0.05). Post-culture, there was a significant increase in ATM expression in transgender non-growing oocytes compared to control (98.5% vs 77.8%, p < 0.05) and a less marked decline in RAD51 expression(p < 0.05). The expression of MRE-11 in control non-growing oocytes dramatically declined (100% to 58.2%, p < 0.05), unlike in transgender tissue where expression was comparable to D0. Limitations, reasons for caution A large number of follicles have been analysed, but only from a small number of ovaries. DNA damage at D0 and after 6 days of culture may not reflect DNA damage and repair capacity at later stages of follicle growth. The effect of duration of testosterone treatment was not investigated. Wider implications of the findings These data indicate that high circulating concentrations of testosterone have previously unrecognised effects on the primordial and small-growing follicles of the ovary. These results may have implications for transgender men receiving gender-affirming therapy prior to considering pregnancy or fertility preservation measures. Trial registration number n/a

BackgroundIncreasingly, health policy-makers and managers all over the world look for alternative forms of organisation and governance in order to add more value and quality to their health systems. In recent years, the central government in England mandated several cross-sector health initiatives based on collaborative governance arrangements. However, there is little empirical evidence that examines local implementation responses to such centrally-mandated collaborations.MethodsData from the national study of Health Innovation and Education Clusters (HIECs) are used to provide comprehensive empirical evidence about the implementation of collaborative governance arrangements in cross-sector health networks in England. The study employed a mixed-methods approach, integrating both quantitative and qualitative data from a national survey of the entire population of HIEC directors (N = 17; response rate = 100%), a group discussion with 7 HIEC directors, and 15 in-depth interviews with HIEC directors and chairs.ResultsThe study provides a description and analysis of local implementation responses to the central government mandate to establish HIECs. The latter represent cross-sector health networks characterised by a vague mandate with the provision of a small amount of new resources. Our findings indicate that in the case of HIECs such a mandate resulted in the creation of rather fluid and informal partnerships, which over the period of three years made partial-to-full progress on governance activities and, in most cases, did not become self-sustaining without government funding.ConclusionThis study has produced valuable insights into the implementation responses in HIECs and possibly other cross-sector collaborations characterised by a vague mandate with the provision of a small amount of new resources. There is little evidence that local dominant coalitions appropriated the central HIEC mandate to their own ends. On the other hand, there is evidence of interpretation and implementation of the central mandate by HIEC leaders to serve their local needs. These findings augur well for Academic Health Science Networks, which pick up the mantle of large-scale, cross-sector collaborations for health and innovation. This study also highlights that a supportive policy environment and sufficient time would be crucial to the successful implementation of new cross-sector health collaborations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-014-0552-y) contains supplementary material, which is available to authorized users.

Children who have been maltreated are at increased risk of further maltreatment. Identification of those at highest risk of further maltreatment is a priority for professionals working in child protection services. The current study is intended to consolidate and expand on previous work on recurrence of child maltreatment. It has sought to identify risk factors for maltreatment recurrence in the recent literature in the expectation that this may help in the practical identification of children at risk. We conducted a systematic review of cohort studies published between 2003 and 2009, identifying factors associated with maltreatment recurrence in children. Studies included demonstrated differing levels of substantiation of maltreatment. Fifteen studies met inclusion criteria but showed significant heterogeneity, varying in setting, recruitment of subjects, types of maltreatment considered and length of follow-up. Previous findings were replicated and expanded in the current study in relation to a range of factors, including rates of maltreatment recurrence, maltreatment types, frequency of previous episodes of maltreatment, child and family considerations, home environment and service provision. Factors were identified irrespective of level of maltreatment substantiation. This study provides further systematic evidence of the existence of a number of factors associated with child maltreatment recurrence. It points to the possibility of practical application of its findings within the wider context of decision making in child protection services, with the ultimate aim of reducing recurrence of maltreatment in individual cases.

Two suspected cases of hepatitis A have been reported in a 40 year old man and his 7 year old son who are part of a travelling community in southeast England