906 research outputs found

    Identifying Pathways to Support British Victims of Modern Slavery towards Safety and Recovery: A Scoping Study

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    Since 2013, the number of British nationals referred into the National Referral Mechanism (NRM) as potential victims of modern slavery has increased year on year, rising from 90 in 2013 to 3,952 in 2021. These figures include potential adult and child victims, referred for labour, criminal and sexual exploitation as well as domestic servitude. The largest proportion of these referrals in 2021 was for criminal exploitation involving children, representing 55% of all referrals of British nationals. Recent studies have begun to uncover the experiences of British nationals who are exploited in modern slavery, including findings that British survivors are failed by the current support system (see Centre for Social Justice and Justice and Care report).Through analysis of data collected via surveys, interviews with survivors, support practitioners and criminal justice professionals, and a review of case law and legislation, this scoping study investigated the pathways to support for British nationals who are potential victims of modern slavery

    Tunable length of cyclic peptide–polymer conjugate self-assemblies in water

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    Polymers conjugated to cyclic peptides capable of forming strong hydrogen bonds can self-assemble into supramolecular bottlebrushes even in aqueous solutions. However, controlling the aggregation of these supramolecular assemblies remains an obstacle that is yet to be overcome. By introducing pH-responsive poly(dimethylamino ethyl methacrylate) (pDMAEMA) arms, the repulsive forces were tuned by adjusting the degree of protonation on the polymer arms. Neutron scattering experiments demonstrated that conjugates in an uncharged state will self-assemble into supramolecular bottlebrushes. Reducing the pH in the system led to a decrease in the number of aggregation, which was reversible by addition of base. Potentiometric titration showed a correlation between the number of aggregation and the degree of ionization of the pDMAEMA arms. Hence, a balance between the strength of the hydrogen bonds and the repulsive electrostatic interactions determines the number of aggregation and extent of self-assembly. The presented work demonstrates that conjugate self-association can be controlled by tuning the charge density on the conjugated polymer arms, paving the way for the use of responsive cyclic peptide conjugates in pharmaceutical applications

    Comparison of 25‐hydroxyvitamin D concentration in chimpanzee dried blood spots and serum

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    BackgroundDried blood spots (DBS) are used in human medicine to measure total 25‐hydroxyvitamin D (25‐OHD) in the blood. However, this easy and affordable sampling technique has not been evaluated in primates to measure vitamin D concentrations.ObjectivesWe aimed to compare 25‐OHD measurements in chimpanzee serum at two different laboratories and determine the precision and accuracy of the DBS method by comparing DBS and serum results.MethodsBlood samples from 17 captive chimpanzees were collected, and 25‐OHD3 and 25‐OHD2 were measured in serum at two accredited laboratories using liquid chromatography‐tandem mass spectrometry. The same analytes were measured on DBS cards, and results were compared with that of serum. Data were assessed using the Spearman correlation, Deming regression, and Bland‐Altman analyses. ResultsThe correlation coefficient between the two measurements in serum was r s = .51 (P = .04), and the mean bias was −1.25 ± 14.83. When comparing 25‐OHD concentrations measured in DBS and serum at the same laboratory, the r s was 0.7 (P = .002), and the mean bias was 1.42 ± 14.58. Estimated intra‐assay and inter‐assay coefficients of variation for DBS results were 6% and 12.6%, respectively. ConclusionsAlthough substantial analytical variability was found in 25‐OHD measurements regardless of the sample type, the identification of both constant and proportional error and wider limits of agreement with the DBS technique makes the interpretation of DBS results challenging, especially for values close to clinical cut‐off points. The DBS and serum methods were not interchangeable, and further studies are needed to validate DBS samples for vitamin D measurements in chimpanzees

    Identifying Pathways to Support British Victims of Modern Slavery towards Safety and Recovery: A Scoping Study

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    Since 2013, the number of British nationals referred into the National Referral Mechanism (NRM) as potential victims of modern slavery has increased year on year, rising from 90 in 2013 to 3,952 in 20213. These figures include potential adult and child victims, referred for labour, criminal and sexual exploitation as well as domestic servitude. The largest proportion of these referrals in 2021 was for criminal exploitation involving children, representing 55% of all referrals of British nationals. Recent studies have begun to uncover the experiences of British nationals who are exploited in modern slavery, including findings that British survivors are failed by the current support system (see Centre for Social Justice and Justice and Care report). Through analysis of data collected via surveys, interviews with survivors, support practitioners and criminal justice professionals, and a review of case law and legislation, this scoping study investigated the pathways to support for British nationals who are potential victims of modern slavery. Project aims: ‱ Understand the recovery needs and experiences of British nationals who are victims/survivors of modern slavery ‱ Identify gaps in support provided to British nationals ‱ Understand barriers including why British nationals may not be identified as victims and may not engage with support ‱ Understand the experiences of British nationals of the Criminal Justice System (CJS) and the impact of potential erroneous prosecutions ‱ Improve knowledge about what support for British nationals should look like to enable their recovery and prevent re-trafficking Key Findings ‱ Missed opportunities by professionals in statutory and non-statutory services resulted in a failure to identify and protect British nationals, including children, prior to exploitation. ‱ Professionals who interact with British nationals during exploitation are failing to recognise them as potential victims of modern slavery due to misunderstandings about who can be a victim of modern slavery. ‱ If correctly identified as potential victims, British nationals are often not referred into the NRM due to misunderstandings about who the NRM is for. ‱ There is a lack of knowledge of the statutory entitlements of British nationals resulting in missed opportunities to offer access to relevant support both in and out of the NRM. ‱ Post-exploitation, British survivors fall through significant gaps in support offered both through the Modern Slavery Victim Care Contract (MSVCC) and under other statutory services. ‱ British nationals often present with complex needs (mental health and substance misuse, historical exploitation, criminal exploitation). Current systems, including mental health and criminal justice, both in and out of the NRM, are not set up to support this complexity. ‱ Recovery pathways aimed at building resilience to reduce the risk of re-exploitation, based on understanding of their experiences, needs and statutory entitlements, have not been established for British nationals. ‱ Survivors are experts by experience. Their experiences of the gaps in identification, support and justice are currently not being employed to inform the creation of improved pathways to recovery

    Child and parent outcomes following parent interventions for child emotional and behavioral problems in autism spectrum disorders: A systematic review and meta-analysis

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    There is growing interest in the development of behavioral parent interventions targeting emotional and behavioral problems in children with autism spectrum disorders. Such interventions have potential to improve a number of child and parental well-being outcomes beyond disruptive child behavior. This systematic review and meta-analysis assesses evidence for the efficacy of behavioral parent interventions for disruptive and hyperactive child behavior in autism spectrum disorders, as well as parenting efficacy and stress. A total of 11 articles from nine randomized controlled trials were included. Sufficient data were available to calculate standardized mean difference and show favorable effects of behavioral parent interventions on parent-reported measures of child disruptive behavior (standardized mean difference = 0.67), hyperactivity (standardized mean difference = 0.31) and parent stress (standardized mean difference = 0.37); effects on parent efficacy are less clear (standardized mean difference = 0.39, p = 0.17). There were insufficient data to explore intervention effects on internalizing behavior in autism spectrum disorders, parenting behaviors, or observational and teacher-reported outcomes, providing important avenues for future research. This review adds to growing evidence of the efficacy of behavioral parent interventions for child behavior and parental well-being in autism spectrum disorders (Prospero: CRD42016033979)

    Self-management for osteoarthritis of the knee: Does mode of delivery influence outcome?

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    Background Self-management has become increasingly popular in the management of chronic diseases. There are many different self-management models. Meta analyses of arthritis self-management have concluded that it is difficult to recommend any one program in preference to another due to inconsistencies in the study designs used to evaluate different programs. The Stanford Arthritis Self-Management Program (ASMP), most commonly delivered by trained lay leaders, is a generic program widely used for people with rheumatological disorders. We have developed a more specific program expressly for people with osteoarthritis of the knee (OAKP). It includes information designed to be delivered by health professionals and results in improvements in pain, function and quality of life. Aim: To determine whether, for people with osteoarthritis (OA) of the knee, the OAKP implemented in a primary health care setting can achieve and maintain clinically meaningful improvements in more participants than ASMP delivered in the same environment. Methods/Design The effectiveness of the programs will be compared in a single-blind randomized study. Participants: 146 participants with established OA knee will be recruited. Volunteers with coexistent inflammatory joint disease or serious co-morbidities will be excluded. Interventions: Participants will be randomised into either OAKP or ASMP groups and followed for 6 months. Measurements: Assessments will be immediately before and after the intervention and at 6 months. Primary outcome measures will be WOMAC and SF-36 questionnaires and a VAS for pain. Secondary outcomes will include balance, tested using a timed single leg balance test and a timed step test and self-efficacy. Data will be analysed using repeated measures ANOVA. Discussion With an aging population the health care costs for people with arthritis are ever increasing. Although cost analysis is beyond the scope of this study, it is reasonable to expect that costs will be greater when health professionals deliver self-management programs as opposed to lay leaders. Consequently it is critical to examine the relative effectiveness of the primary care management strategies available for OA

    Short and medium-term effects of an education self-management program for individuals with osteoarthritis of the knee, designed and delivered by health professionals: A quality assurance study

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    <p>Abstract</p> <p>Background</p> <p>Self-management (SM) programs are effective for some chronic conditions, however the evidence for arthritis SM is inconclusive. The aim of this case series project was to determine whether a newly developed specific self-management program for people with osteoarthritis of the knee (OAK), implemented by health professionals could achieve and maintain clinically meaningful improvements.</p> <p>Methods</p> <p><it>Participants: </it>79 participants enrolled; mean age 66, with established osteoarthritis of the knee. People with coexisting inflammatory joint disease or serious co-morbidities were excluded.</p> <p><it>Intervention: </it>6-week disease (OA) and site (knee) specific self-management education program that included disease education, exercise advice, information on healthy lifestyle and relevant information within the constructs of self-management. This program was conducted in a community health care setting and was delivered by health professionals thereby utilising their knowledge and expertise.</p> <p><it>Measurements: </it>Pain, physical function and mental health scales were assessed at baseline, 8 weeks, 6 and 12 months using WOMAC and SF-36 questionnaires. Changes in pain during the 8-week intervention phase were monitored with VAS.</p> <p>Results</p> <p>Pain improved during the intervention phase: mean (95% CI) change 15 (8 to 22) mm. Improvements (0.3 to 0.5 standard deviation units) in indices of pain, mental health and physical functioning, assessed by SF-36 and WOMAC questionnaires were demonstrated from baseline to 12 months.</p> <p>Conclusion</p> <p>This disease and site-specific self-management education program improved health status of people with osteoarthritis of the knee in the short and medium term.</p

    Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure

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    BACKGROUND: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10-15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients.ŠMETHODOLOGY/PRINCIPAL FINDINGS: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LOD(max) of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations.ŠCONCLUSIONS/SIGNIFICANCE: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function

    RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation

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    The RAD51 paralogues act in the homologous recombination (HR) pathway of DNA repair. Human RAD51C (hRAD51C) participates in branch migration and Holliday junction resolution and thus is important for processing HR intermediates late in the DNA repair process. Evidence for early involvement of RAD51 during DNA repair also exists, but its function in this context is not understood. In this study, we demonstrate that RAD51C accumulates at DNA damage sites concomitantly with the RAD51 recombinase and is retained after RAD51 disassembly, which is consistent with both an early and a late function for RAD51C. RAD51C recruitment depends on ataxia telangiectasia mutated, NBS1, and replication protein A, indicating it functions after DNA end resection but before RAD51 assembly. Furthermore, we find that RAD51C is required for activation of the checkpoint kinase CHK2 and cell cycle arrest in response to DNA damage. This suggests that hRAD51C contributes to the protection of genome integrity by transducing DNA damage signals in addition to engaging the HR machinery
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