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Background: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. Methods: A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. Results: An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The 'ALABAMA unit' within SystmOne was also created and provided a secure efficient environment to access participants' EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. Conclusions: ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. Trial registration: ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216. [ABSTRACT FROM AUTHOR]

Background: Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined. Methods: This study aims to assess the healthcare utilisation of individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records. Results: We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74–8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48–1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58–29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73–16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20–8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39–1.50). The long COVID group costs approximately £2500 per person per year (predicted mean cost: £2562.50, 95% CI: £2335.60–£2819.22), and the comparator group costs £1500 (predicted mean cost: £1527.43, 95% CI: £1404.33–1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group. Conclusions: Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID. [ABSTRACT FROM AUTHOR]

Introduction: Usefulness of hysteroscopy before assisted reproductive technique (ART) was considered debatable. However, over the last decade, several new trials have been added to available literature. We aimed to assess the impact of diagnostic and operative hysteroscopy on reproductive outcomes of infertile women with and without intrauterine abnormalities. Materials and Methods: MEDLINE, Scopus, SciELO, Embase, Cochrane Library at CENTRAL, PROSPERO, CINAHL, grey literature, conference proceedings, and international controlled trials registries were searched without temporal, geographical, or language restrictions. Randomized controlled trials (RCTs) of infertile women comparing hysteroscopy versus no hysteroscopy prior to the first ART or after at least one failed attempt were included. RCTs of infertile women with intrauterine pathology comparing diagnostic versus operative hysteroscopy were included in separate analysis. Random-effect meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Grading of Recommendations, Assessment, Development and Evaluation and Cochrane criteria were used for quality of evidence and risk of bias assessment. Primary outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy (CPR) and pregnancy loss rate. Results: Fifteen studies (5,038 women) were included. Compared to no hysteroscopy before first or after failed ART attempts, moderate-quality evidence showed that hysteroscopy increased the LBR (relative risk [RR] 1.24, 95% confidence interval [CI] 1.09–1.43, I2 = 21%), confirmed by subgroup analysis for women with failure after one or more ART cycles (RR 1.43, 95% CI: 1.19–1.72, I2 = 0%) but not before the first ART. Moderate-quality evidence showed that it increased the CPR (RR 1.36, 95% CI: 1.18–1.57; I2 = 51%), confirmed in subgroup analysis for both implantation failure (RR 1.40, 95% CI: 1.12–1.74, I2 = 52%) and before first ART (RR 1.32, 95% CI: 1.11–1.57, I2 = 42%). Low-quality data suggest that operative hysteroscopy increases CPR when used to treat intrauterine pathologies (RR 2.13, 95% CI: 1.56–2.92, I2 = 0%). Conclusions: Although moderate-quality evidence supports performing hysteroscopy before ART in women with history of implantation failure, hysteroscopic evaluation of uterine cavity should be considered a first-line technique in all infertile women undergoing ART. Additional high-quality RCTs are still needed, particularly to assess yield during couple's initial evaluation even before ART is considered. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency is a common problem in subfertile women. The influence of iron status on unexplained infertility is unknown. Methods: In a case-control study, 36 women with unexplained infertility and 36 healthy non-infertile controls were included. Parameters of iron status including serumferritin and a serum ferritin <30 µg/dL served as main outcome parameters. Results: Women with unexplained infertility demonstrated a lower transferrin saturation (median 17.3%, IQR 12.7-25.2 versus 23.9%, IQR 15.4-31.6; p= 0.034) and a lower mean corpuscular hemoglobin concentration (median 33.6 g/dL, IQR 33.0-34.1 versus 34.1 g/dL, IQR 33.2-34.7; p= 0.012). Despite the fact that there was no statistically significant difference in median ferritin levels (p= 0.570), women with unexplained infertility had ferritin levels <30µg/L more often (33.3%) than controls (11.1%; p= 0.023). In a multivariate model, unexplained infertility and abnormal thyroid antibodies were associated with ferritin <30µg/L (OR 4.906, 95%CI: 1.181-20.388; p= 0.029 and OR 13.099; 2.382-72.044; p= 0.029, respectively). Conclusion: Ferritin levels <30µg/L were associated with unexplained infertility andmight be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted. [ABSTRACT FROM AUTHOR]

Background: Women with functional hypothalamic amenorrhea (FHA) reveal polycystic ovarian morphology (PCOM) in up to 50%. If stress sensitivity in women with polycystic ovary syndrome (PCOS) is the reason why PCOS women are prone to develop FHA, patients with FHA caused by stress should reveal PCOM more often. Methods: In a retrospective cohort study, 38 stress-associated and 38 excessive exercise-induced FHA women were included. The main outcome parameter was PCOM. In addition, the focus was on general patient characteristics as well as on prolactin, dehydroepiandrosterone-sulphate (DHEAS), and anti-Mullerian hormone (AMH). Results: PCOM was found in 34/76 patients (44.7%). The stress group showed a higher prevalence of PCOM than the excessive exercise group (57.9% versus 31.6%, p = 0.019) as well as higher prolactin levels (median 13.2ng/mL versus 11.7ng/mL, p = 0.008) and a trend towards higher DHEAS levels (p = 0.058). Conclusions: In FHA women, the PCOM prevalence was significantly higher in the stress-group than in the excessive exercise-group. The well-known stress sensitivity in women with PCOS might explain why PCOS women are prone to develop FHA as well as the high PCOM prevalence in FHA women. [ABSTRACT FROM AUTHOR]

Postoperative intraabdominal adhesions can occur after more than 90% of gynecologic surgeries. They not only cause chronic pelvic pain and small bowel obstruction, but are also one of the main reasons for infertility. Adhesions are not only a burden for the affected patients, but are also a burden for the healthcare system, since the treatment of adhesion-associated complications costs a considerable amount of money. The gold standard for the diagnosis of adhesions is by laparoscopy, although other methods, such as transvaginal hydro-laparoscopy, are being discussed as better alternatives. Ideally, adhesions are avoided inherently, by operating carefully and by using microsurgical principles. If this is not possible, gel barriers have been shown to be successful in reducing postoperative adhesions. [ABSTRACT FROM AUTHOR]

There are limited data on how non-infectious risk factors influence tubal patency in women with subfertility. With hormonal shifts influencing tubal secretions, it has been argued that subfertile women with polycystic ovary syndrome (PCOS) have lower tubal patency. In a retrospective study, 216 women, who underwent diagnostic evaluation for PCOS and infertility, were included. Fallopian tube patency was tested using HSG, HyCoSy, and laparoscopic chromopertubation in 171 (79.2%), 28 (13.0%), and 17 (7.9%), respectively. Bilateral patency was found in 193 women (89.4%), unilateral patency in 13 (6.0%) and bilateral occlusion in 10 (4.6%) patients. Women with PCOS phenotypes C (odds ratio, OR 0.179, 95% CI: 0.039–0.828) and D (OR 0.256, 95% CI: 0.069–0.947) demonstrated lower risks for Fallopian tube occlusion. In conclusion, our data suggest that about 5% of infertile women with PCOS also have bilateral tubal occlusion, which seems similar to the rate in non-subfertile women. With 11% of participants having unilateral or bilateral tubal occlusion, this should reassure women with PCOS that their hormonal challenges do not seem to increase their risk for tubal factor subfertility. [ABSTRACT FROM AUTHOR]

Endometriosis seems to have a strong negative effect on female fertility. The aim of this study was to assess the rate of tubal occlusion diagnosed via laparoscopic chromopertubation in infertile women with endometriosis and compare the results to infertile women without endometriosis. In this retrospective cohort study, 275 infertile women with endometriosis and 49 infertile women without endometriosis undergoing diagnostic laparoscopy for primary or secondary infertility with chromopertubation at the Medical University of Vienna between January 2012 and December 2020 have been investigated. During the laparoscopic assessment of tubal patency, significantly more fallopian tubes were occluded in the endometriosis group compared to the control group (25.8 versus 15.3%; p = 0.029). Unilateral and bilateral occlusion was found significantly more often in patients with endometriosis (p = 0.021). In the multivariate analysis, only the rASRM stage (the revised classification of endometriosis by the American Society for Reproductive Medicine) showed a significant association with bilateral occlusion (OR 1.400, 95%CI: 1.018–1.926; p = 0.038). Both a higher rASRM stage (OR 2.181, 95%CI: 1.191–3.995; p = 0.012) and secondary infertility (OR 1.514, 95%CI: 1.156–1.983; p = 0.003) were associated with an increased risk for any kind of fallopian tube occlusion. Endometriosis seems to be associated with an increased risk for fallopian tube occlusion. The rate of tubal occlusion increased significantly with the rASRM stage. [ABSTRACT FROM AUTHOR]

For women with polycystic ovarian syndrome (PCOS) and infertility, stimulation with the aromatase-inhibitor letrozole has been recommended as a first-line for ovulation induction. Calcium-associated signaling has also been a component for other ovulation induction and superovulation medications. This study's aim was to evaluate parameters of calcium metabolism in PCOS women. In a prospective cohort study, 61 anovulatory, infertile PCOS patients who underwent letrozole stimulation were included. Outcome measures were: follicular maturation after letrozole stimulation; parathyroid hormone (PTH); 25-hydroxyvitamin D3 (25OHD3); serum levels of calcium, phosphorus, magnesium, albumin, and total protein. Successful recruitment of a dominant follicle was achieved in 35 patients (57.4%). Women with and without successful follicular development did not differ in serum levels of PTH (38.4 ± 19.7 vs. 39.6 ± 16.2 pg/mL), 25OHD3 (62.5 ± 32.1 vs. 65.4 ± 30.9 nmol/L), calcium (2.36 ± 0.08 vs. 2.37 ± 0.12 mmol/L), or protein (70.2 ± 13.3 vs. 74.0 ± 3.7 g/L), respectively (p > 0.05). However, women who were not responsive to letrozole for ovulation induction demonstrated higher anti-Müllerian hormone (AMH) levels (9.7 ± 4.7 vs. 5.0 ± 3.2 ng/mL, p = 0.005). In conclusion, the success of letrozole stimulation in women with PCOS is independent from calcium metabolism parameters. However, AMH levels seem predictive of medication resistance. [ABSTRACT FROM AUTHOR]

Background: Quality of life (QOL) and psychological health has been reported to be decreased among women with gynecological conditions such as uterine fibroids (UFs). Materials and Methods: Women enrolled in the Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry, receiving procedural therapy for symptomatic UFs, were eligible for this analysis if they completed a series of health-related QOL surveys administered at three time points (baseline, 6–12 weeks postprocedure, and 1 year postprocedure; n = 1486). Ethical approval for this study was obtained at each recruiting site and the coordinating center (NCT02260752, clinicaltrials.gov). Results: More than 26% (n = 393) of women reported moderate anxiety/depression on the baseline anxiety/depression domain of the Euro-QOL 5-dimension instrument. At both the 6–12 weeks and 1-year postprocedural follow-up, there was significant improvement in the UF QOL symptom severity score (p < 0.001, p < 0.001), the total UF symptom QOL score (p < 0.001, p < 0.001), and the Euro-QOL 5-dimension visual analog scale (p < 0.001, p = 0.004) compared with the preprocedural baseline scores. The reporting of anxiety/depression decreased by 66.4% among women who were at baseline, whereas 5.6% of women previously reporting no anxiety/depression reported anxiety/depression at the 1-year follow-up. Conclusion: UF symptoms were more severe among women reporting anxiety/depression at baseline. At the 1-year follow-up, health-related QOL scores improved among all women and the prevalence of anxiety/depression decreased in most, but not all women, whereas severity of anxiety/depression worsened in a small percentage of women (5.6%). Overall, these results suggest that UF treatment improves symptoms of anxiety/depression associated with symptomatic UFs. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether an increase in cul de sac (CDS) fluid after hysteroscopy is predictive of tubal patency. Methods: In a prospective clinical cohort study, 115 subfertile women undergoing laparoscopic and hysteroscopic surgery at the Medical University of Vienna were invited to participate. The primary outcome was determining whether an increase in fluid in the pouch of Douglas was reflective of unilateral or bilateral tubal patency. Vaginal sonography before and after hysteroscopy was performed to detect fluid in the pouch of Douglas, directly followed by laparoscopy with chromopertubation. Results: Laparoscopic chromopertubation revealed bilateral Fallopian tube occlusion in 28 women (24.3%). Twenty-seven/40 patients (67.5%) with no fluid shift had bilateral occlusion during the consecutive laparoscopy (p < 0.001). One/75 patients (1.3%) showing a fluid shift had bilateral occlusion (sensitivity of a present fluid shift for uni- or bilateral patency 85.1%, 95% CI: 81.7–99.9, specificity: 96.4%, 95% CI: 75.8–91.8). Intracavitary abnormalities (odds ratio, OR, 0.038; p = 0.030) and adhesions covering one or both tubes (OR 0.076; p = 0.041) increased the risk for a false abnormal result, i.e., uni- or bilateral tubal patency despite the lack of a fluid shift. Conclusion: When CDS fluid does not change after hysteroscopy, this is a sensitive test for tubal occlusion and further testing may be warranted. However, if there is an increase in CDS fluid after hysteroscopy, particularly for a patient without fluid present prior, this is both sensitive and specific for unilateral or bilateral tubal patency. [ABSTRACT FROM AUTHOR]

This article reports on a study of practitioners' use of In-the-Picture – a reflective, observational approach – when delivering early intervention programmes to young disabled children. To date, In-the-Picture has been used mainly by researchers to study interactions and learning between young children, practitioners and the children's parents in home and early childhood settings. Practitioners involved in this early research had expressed an interest in using the tool themselves. This project aimed to engage such potential users, support them in using the approach and gain evidence of its impact upon their practice. In-the-Picture facilitates listening and communication between adults and children with learning disabilities. It is based upon a sociocultural understanding of learning, seeing the parents, children and practitioners as agents participating in an emerging teaching and learning process. It derives from a qualitative grounded research method which enables the researcher to consider the child's perspective, through the use of first-person narrative observation, photography of the child's focus of attention and reflective discussion with the child, practitioners and family. This study involved 10 Portage services in England, who provide weekly home visits with a focus on supporting play and communication with their child. Training was delivered to over 80 Portage Home Visitors across these 10 services. A selected sample of 20 practitioners, 2 from each service, was interviewed after 6 weeks and again within focus groups after 3 months. All interviewees used the approach in their own way and identified challenges in its use, but In-the-Picture was seen as relevant and valuable by all the participants, producing changes in thinking and practice, while proving flexible and simple to use. The study also exemplified how current early-intervention working practices in England limit the opportunity to engage with the child's perspective and how practitioners value having the opportunity to do so. [ABSTRACT FROM AUTHOR]

A man now aged 80 years has received specialist care for stage 1A mycosis fungoides for 58 years. The disease developed in childhood. Long-term follow-up (>30 years) of patients with mycosis fungoides is infrequently described in the world literature. The disease in this patient was limited to 5 areas, but these were large (up to 25 cm in diameter). The rest of the skin was normal clinically. All 5 areas were treated separately with electron beam therapy (3–4 MeV) to a dose of 30 Gy in 15 fractions over 3 weeks between 2000 and 2005. Complete regression was obtained in all 5 areas, and the patient has been in complete remission for 15 years after living with the disease previously for over 40 years. [ABSTRACT FROM AUTHOR]

Background: Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost. Our objective was to examine the diagnostic outcomes of a one- versus two-assay serological testing strategy. These data were used to inform recommendations in the 2017 WHO Guidelines on hepatitis B and C testing.Methods: Few published studies have compared diagnostic outcomes for one-assay versus two-assay serological testing strategies for HBsAg and anti-HCV. Therefore, the principles of Bayesian statistics were used to conduct a modelling exercise to examine the outcomes of a one-assay versus two-assay testing strategy when applied to a hypothetical population of 10,000 individuals. The resulting model examined the diagnostic outcomes (true and false positive diagnoses; true and false negative diagnoses; positive and negative predictive values as a function of prevalence; and total tests required) for both one-assay and two-assay testing strategies. The performance characteristics assumed for assays used within the testing strategies were informed by WHO prequalification assessment findings and systematic reviews for diagnostic accuracy studies. Each of the presumptive testing strategies (one-assay or two-assay) was modelled at varying prevalences of HBsAg (10%, 2% and 0.4%) and of anti-HCV (40%, 10%, 2% and 0.4%), aimed at representing the range of testing populations typically encountered in WHO Member States. When the two-assay testing strategy was considered, the model assumed the independence of the two assays.Results: Modeling demonstrated that applying a single assay (HBsAg or anti-HCV), even with high specificity (99%), may result in considerable numbers of false positive diagnoses and low positive predictive values (PPV), particularly in lower prevalence settings. Even at very low prevalences shifting to a two-assay testing strategy would result in a PPV approaching 1.0. When test sensitivity is high (>99%) false negative reactions are rare at all but the highest prevalences; but a two-test strategy might yield more false negative diagnoses. The order in which the tests are used has no impact on the overall accuracy of a two-assay strategy though it may impact the total number of tests needed to complete the diagnostic strategy, incurring added cost and complexity. HBsAg assays may have a low sensitivity (<90%), and result in large numbers of false negative diagnoses, particularly in high prevalence settings, which would be exacerbated in the two-assay testing strategy. In contrast, most anti-HCV assays have high sensitivity and lead to fewer false negative results, both in the one-assay and two-assay testing strategies. At prevalences ≤2% the number of tests needed using a second assay was nearly always small, at <300 per 10,000 individuals tested, making sustainability of a second assay uncertain in such a setting.Conclusions: A key public health objective of an effective testing strategy is to identify all individuals who would benefit from treatment. Therefore, a strategy that prioritizes a high NPV (minimal false negatives) may be acceptable even if the PPV is suboptimal (some false positives) as the implementation of such a public health programme must also take account of other factors such as costs, feasibility, impact on testing uptake and linkage to care, and consequences of a false-positive test. This rationale informed the development of the WHO Viral Hepatitis Testing Guidelines, with a conditional recommendation for a one-assay serological testing strategy in most testing settings and populations (≥0.4% prevalence in population tested). A one-test strategy results in few failures to diagnose infection and, although it is associated under most assumptions with a sub-optimal PPV, benefits include greater simplicity, easier implementation, lower costs and better feasibility, uptake and linkage to care. Furthermore, prior to antiviral therapy all those diagnosed either HBsAg or anti-HCV positive will require confirmation of viræmia, preventing unnecessary treatment of those who may be false positive on serology. For HBsAg, in low-prevalence settings (≤0.4%), a second recommendation was made to consider a two-assay testing strategy, using a confirmatory neutralization step or a second different HBsAg assay. [ABSTRACT FROM AUTHOR]

The article focuses on future of coercive interrogation and domestic concerns about police violence and conditions in prisons and prohibition against torture. It mentions Department of Defense officials began to use mentally and physically violent interrogation tactics and detained during military and counter-terror operations. It also mentions section that appears to reject torture in all circumstances support of human rights.

Background: frailty is an especially problematic expression of population ageing. International guidelines recommend routine identification of frailty to provide evidence-based treatment, but currently available tools require additional resource. Objectives: to develop and validate an electronic frailty index (eFI) using routinely available primary care electronic health record data. Study design and setting: retrospective cohort study. Development and internal validation cohorts were established using a randomly split sample of the ResearchOne primary care database. External validation cohort established using THIN database. Participants: patients aged 65-95, registered with a ResearchOne or THIN practice on 14 October 2008. Predictors: we constructed the eFI using the cumulative deficit frailty model as our theoretical framework. The eFI score is calculated by the presence or absence of individual deficits as a proportion of the total possible. Categories of fit, mild, moderate and severe frailty were defined using population quartiles. Outcomes: outcomes were 1-, 3- and 5-year mortality, hospitalisation and nursing home admission. Statistical analysis: hazard ratios (HRs) were estimated using bivariate and multivariate Cox regression analyses. Discrimination was assessed using receiver operating characteristic (ROC) curves. Calibration was assessed using pseudo-R estimates. Results: we include data from a total of 931,541 patients. The eFI incorporates 36 deficits constructed using 2,171 CTV3 codes. One-year adjusted HR for mortality was 1.92 (95% CI1.81-2.04) for mild frailty 3.10 (95% CI 2.91-3.31) for moderate frailty and 4.52 (95% CI 4.16-4.91) for severe frailty. Corresponding estimates for hospitalisation were 1.93 (95% CI 1.86-2.01), 3.04 (95% CI 2.90-3.19) and 4.73 (95% CI 4.43-5.06) and for nursing home admission were 1.89 (95% CI 1.63-2.15), 3.19 (95% CI 2.73-3.73) and 4.76 (95% CI 3.92-5.77), with good to moderate discrimination but low calibration estimates. Conclusions: the eFI uses routine data to identify older people with mild, moderate and severe frailty, with robust predictive validity for outcomes of mortality, hospitalisation and nursing home admission. Routine implementation of the eFI could enable delivery of evidence-based interventions to improve outcomes for this vulnerable group. [ABSTRACT FROM AUTHOR]

This paper reports on a small-scale study of the social interactions between six children labelled with special educational needs and their peers in their respective early years settings. Data from play observations, photographs and staff interviews is used to examine the dynamics of the connections that they make with other children. The position of these six children as active agents in making decisions about their peer interactions is highlighted and the ways that this agency is expressed is analysed. By focusing on the personal strategies that the children use to make social connections the findings contribute to the developing understanding of children's relationships within inclusive early years settings. In particular compatible play interests and personalities are identified as significant factors that attract children to one another in this case study. It also emerged that recurrent playmates did not feature consistently in the social exchanges involving this group of children. This factor is considered in the context of it being indicative of the social connections that children labelled with special educational needs pursue. Suggestions for further investigation are proposed and key practice messages offered around developing awareness and facilitation of social connections between children. [ABSTRACT FROM PUBLISHER]

To determine uptake of home sampling kit (HSK) for STI/HIV compared to clinic-based testing, whether the availability of HSK would increase STI testing rates amongst HIV infected MSM, and those attending a community-based HIV testing clinic compared to historical control. Prospective observational study in three facilities providing STI/HIV testing services in Brighton, UK was conducted. Adult MSM attending/contacting a GUM clinic requesting an STI screen (group 1), HIV infected MSM attending routine outpatient clinic (group 2), and MSM attending a community-based rapid HIV testing service (group 3) were eligible. Participants were required to have no symptomatology consistent with STI and known to be immune to hepatitis A and B (group 1). Eligible men were offered a HSK to obtain self-collected specimens as an alternative to routine testing. HSK uptake compared to conventional clinic-based STI/HIV testing in group 1, increase in STI testing rates due to availability of HSK compared to historical controls in group 2 and 3, and HSK return rates in all settings were calculated. Among the 128 eligible men in group 1, HSK acceptance was higher (62.5% (95% CI: 53.5–70.9)) compared to GUM clinic-based testing (37.5% (95% CI: 29.1–46.5)), (p = 0.0004). Two thirds of eligible MSM offered an HSK in all three groups accepted it, but HSK return rates varied (highest in group 1, 77.5%, lowest in group 3, 16%). HSK for HIV testing was acceptable to 81% of men in group 1. Compared to historical controls, availability of HSK increased the proportion of MSM testing for STIs in group 2 but not in group 3. HSK for STI/HIV offers an alternative to conventional clinic-based testing for MSM seeking STI screening. It significantly increases STI testing uptake in HIV infected MSM. HSK could be considered as an adjunct to clinic-based services to further improve STI/HIV testing in MSM. [ABSTRACT FROM AUTHOR]

Müllerian duct anomalies (MDA) occur due to abnormal development of the uterus, cervix, and vagina, many times affecting a woman's ability to conceive and carry a pregnancy to term. The spectrum of possible abnormalities are related to the development of two separate Müllerian systems, which then fuse and subsequently undergo degeneration of the fused segments. This multiphasic development explains the multiple variations within the scheme of MDA classification. The purpose of this article is to review the embryologic development of the Müllerian ducts, relate the development to the most commonly used classification system, and review the magnetic resonance imaging (MRI) assessment of Müllerian duct anomalies. A brief review of the treatment options, as they relate to the imaging diagnosis, will be provided as well. J. Magn. Reson. Imaging 2015;41:1-12. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This paper reports on a pilot study of the social interactions between two children labelled with special educational needs and their peers in an early years setting. Data from play observations and staff interviews are used to examine the dynamics of friendship groups that the two children have developed and the way that they attempt to make new connections with other children. Comparisons between the two children's interactions with their recurrent playmates and less familiar peers are drawn and the significance of their agency in making decisions about developing relationships is highlighted. A theme that also emerges is that staff facilitating rather than directing interactions between the two children and their peers has the most positive impact. Areas for further investigation are suggested including the range of relationships that children identified with special educational needs establish with their peers and the nature of adult support that most effectively supports friendships between all children. [ABSTRACT FROM AUTHOR]

The paper provides a background for the need to address climate change globally. In particular, it shows how the UK has addressed and is approaching the implications of climate change especially for its deemed critical infrastructure and the civil engineering profession. In addition, it sets out UK government responses, legislation background and policy decisions with regard to risk and infrastructure adaptation. It highlights some worldwide examples of climate change issues and recent severe events in the UK, such as storms, high winds, flooding, high and low temperatures and their costly consequences. Reference is made to historical and recent severe weather events and consequences leading to proposed actions for the adaptation of critical infrastructure in the transport, utilities and energy sectors. A description of current UK research programmes addressing climate change issues is included. An outline of how the UK insurance and financial sectors have built climate change into their business operations is also given. [ABSTRACT FROM AUTHOR]

Background Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45. Methods Samples singly infected with HPV16 (n = 226), HPV18 (n = 32), HPV31 (n = 75) or HPV45 (n = 29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3'L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample. Results Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2-26.1; p < 0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0-6.8; p = 0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8-18.0; p < 0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31. Conclusions This study lends support for HPV viral load and CpG methylation status, but not integration status, to be considered as potential biomarkers of cervical disease. [ABSTRACT FROM AUTHOR]

Background: Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45. Methods: Samples singly infected with HPV16 (n = 226), HPV18 (n = 32), HPV31 (n = 75) or HPV45 (n = 29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3'L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample. Results: Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2-26.1; p < 0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0-6.8; p = 0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8-18.0; p < 0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31. Conclusions: This study lends support for HPV viral load and CpG methylation status, but not integration status, to be considered as potential biomarkers of cervical disease. [ABSTRACT FROM AUTHOR]

Inclusion is generally recognised as an ongoing, active process which reflects shifts in policies, practice and values as well as political choices made over long periods of time. Drawing upon research visits set 10 years apart, this study aims to examine how two schools with clear inclusive aspirations and intentions have weathered the last decade and reports on their perception of the journey travelled. Data from the research show that in both cases there was a shift away from practices that were previously seen as being central to the development of inclusion, caused by the interplay between political, pedagogic and social factors. The study also suggests that the pervasive influence of the special education and medical model can shape the extent of change in schools. [ABSTRACT FROM PUBLISHER]

Objective: To describe drug use, sexual risks and the prevalence of blood-borne viral infections among men who inject image and performance enhancing drugs (IPEDs). Design: A voluntary unlinked-anonymous crosssectional biobehavioural survey. Setting: 19 needle and syringe programmes across England and Wales. Participants: 395 men who had injected IPEDs. Results: Of the participants (median age 28 years), 36% had used IPEDs for <5 years. Anabolic steroids (86%), growth hormone (32%) and human chorionic gonadotropin (16%) were most frequently injected, with 88% injecting intramuscularly and 39% subcutaneously. Two-thirds also used IPEDs orally. Recent psychoactive drug use was common (46% cocaine, 12% amphetamine), 5% had ever injected a psychoactive drug and 9% had shared injecting equipment. 'Viagra/Cialis' was used by 7%, with 89% reporting anal/vaginal sex in the preceding year (20% had 5+ female-partners, 3% male-partners) and 13% always using condoms. Overall, 1.5% had HIV, 9% had antibodies to the hepatitis B core antigen (anti-HBc) and 5% to hepatitis C (anti-HCV). In multivariate analysis, having HIV was associated with: seeking advice from a sexual health clinic; having had an injection site abscess/wound; and having male partners. After excluding those reporting male partners or injecting psychoactive drugs, 0.8% had HIV, 8% anti-HBc and 5% anti-HCV. Only 23% reported uptake of the hepatitis B vaccine, and diagnostic testing uptake was poor (31% for HIV, 22% for hepatitis C). Conclusions: Previous prevalence studies had not found HIV among IPED injectors. HIV prevalence in this, the largest study of blood-borne viruses among IPED injectors, was similar to that among injectors of psychoactive drugs. Findings indicate a need for targeted interventions. [ABSTRACT FROM AUTHOR]

β-ionone has been shown to hold potent anti-proliferative and apoptosis induction properties in vitro and in vivo. To investigate the effects of β-ionone on apoptosis initiation and its possible mechanisms of action, we qualified cell apoptosis, proteins related to apoptosis and a phosphatidylinositol 3-kinase (PI3K)-AKT pathway in human gastric adenocarcinoma cancer SGC-7901 cells. The results demonstrated that β-ionone-induced apoptosis in a dose-dependent manner in SGC-7901 cells treated with β-ionone (25, 50, 100 and 200 μmol/L) for 24 h. β-ionone was also shown to induce the expression of cleaved-caspase-3 and inhibit bcl-2 expression in SGC-7901 cells in a dose-dependent manner. The significantly decreased levels of p-PI3K and p-AKT expression were observed in SGC-7901 cells after β-ionone treatments in a time- and dose-dependent manner ( P < 0.01). Thus, the apoptosis induction in SGC-7901 cells by β-ionone may be regulated through a PI3K-AKT pathway. These results demonstrate a potential mechanism by which β-ionone to induce apoptosis initiation in SGC-7901 cells. [ABSTRACT FROM AUTHOR]

Objectives In the UK, although transmission of HIV among injecting drug user (IDUs) has been limited since the 1980s, IDUs and men who have sex with men (MSM) have higher HIV and hepatitis C virus (HCV) prevalences than the general population. MSM who are also IDUs (MSM-IDUs) may therefore have a higher risk of infection than male IDUs who only have sex with women. Methods Analysis of data from a national survey of IDUs attending services (England, Wales and Northern Ireland) between 1998 and 2007, which collected demographic and behavioural data and oral fluid samples for HIV and HCV antibody testing. Results Of the 8671 men who reported injecting drugs and having sex during the preceding year, 96% (8354) were men who only had sex with women (MSW). MSM-IDUs and MSW-IDUs had similar age and number of years of injecting. MSM-IDUs had a higher prevalence of HIV (adjusted OR=4.08, 95% CI 1.9 to 8.5) and of HCV (adjusted OR =1.34, 95% CI 1.1 to 1.8) and were about four times (adjusted OR =3.78, 95% CI 2.9 to 4.9) more likely to have unprotected sex with multiple partners. Among those who injected in the 4 weeks prior to participation, the MSM-IDUs had a higher level of needle/ syringe sharing (adjusted OR =1.72, 95% CI 1.3 to 2.2). Discussion MSM-IDUs have a fourfold higher risk of HIV; HCV prevalence in MSM-IDUs is a third higher than among MSW-IDUs, suggesting elevated risk from injecting and possibly sexual transmission. These findings emphasise the need for public health interventions specifically targeted at MSM-IDUs. [ABSTRACT FROM AUTHOR]

Salt tolerance in plants is a complex trait involving multiple mechanisms. Understanding these mechanisms and their regulation will assist in developing novel strategies to engineer salt-tolerant crops. In the current study, we investigated salt-tolerant mechanisms in soybean ( Glycine max) cultivar WF-7 in comparison to salt-sensitive Union. In vivo and in vitro salt assays demonstrated the salt tolerance of WF-7 at the seedling stage and during germination. After a 10-day 200 mM NaCl treatment, chlorophyll content in Union was reduced by 50 % compared to a 17 % reduction in WF-7. WF-7 was also less affected by abscisic acid (ABA) and NaCl during germination than Union. Upon ABA and NaCl treatment, the ABA-responsive genes SCOF1, ASN1, bZIP44, and AAPK1 are differentially expressed in WF-7 and Union seedlings. These results suggest that salt tolerance in WF-7 is in part regulated through an ABA-dependent pathway. In addition, following a 4-day 200 mM NaCl treatment, WF-7 produced more HO than Union indicating the involvement of reactive oxygen species (ROS) in regulating salt tolerance in WF-7. Yet another mechanism WF-7 employs is withholding toxic chloride (Cl) ions from aerial tissues. Following 200 mM NaCl treatment, Cl accumulation was mostly localized to the roots of WF-7. In contrast, most of the Cl in Union was transported into the stems and leaves. Taken together, our results demonstrated a role of ABA and ROS in regulating salt tolerance in WF-7, and the critical role of Cl in NaCl-induced mortality in soybean. Key message Withholding toxic Cl ions from leaves and, to a lesser extent, stems, confers salt tolerance to soybean WF-7. In addition, ABA and ROS may be involved in salt-stress signal transduction. [ABSTRACT FROM AUTHOR]

The hard shell of a hazelnut is a major waste of the hazelnut industry. The chemical composition, phenolic compounds (total phenolics, tannins and condensed tannins), antioxidant activity (DPPH and ABTS free-radical scavenging assays), and the relationships between phenolic compounds and antioxidant activities of the hazelnut shells from twelve US grown cultivars were investigated to for potential commercial development. Crude fibre accounted for over 85% of total carbohydrate. The shells contained high concentrations of phenolic compounds. Concentrations of phenolic constituents and ABTS•+ -scavenging capacities were significantly higher (P > 0.05) in the Oregon cultivars than their Nebraska counterparts. There were significant positive correlations between ABTS•+ scavenging capacities and the phenolic compounds, whereas DPPH• -scavenging capacity demonstrated a weak negative correlation with ABTS•+ scavenging capacity and the phenolics. The results suggest that hazelnut hard shell may serve as a potential source of natural antioxidants for food applications. [ABSTRACT FROM AUTHOR]