"You can trust me…" Young people going missing and at risk of, or abused through, child sexual exploitation in North Wales

Child sexual exploitation (CSE) has been a strategic priority, and a key area for practice development, for Barnardo’s for over two decades. Within Wales, Barnardo’s Cymru has worked closely with the Welsh Government since 2005 to support the development of robust policy and practice guidance to address CSE in Wales. Established research and practice evidence demonstrates a strong correlation between children and young people going missing and risk of sexual exploitation. Over the past few years, a series of high-profile prosecutions of cases of CSE have raised public awareness of this crime. Networks of perpetrators who had been abusing children and young people over many years were uncovered in Rotherham, Rochdale, Derby, Sheffield, Manchester and Oxford, leading to an increase in activity across all sectors to improve safeguarding and disrupt perpetrators. This research aims to improve understanding of the nature of the relationship between going missing and CSE, and to improve responses to children and young people at risk. Although this issue has been considered at a UK level, very little research into children and young people who go missing and the link between going missing and risk of CSE has been undertaken in Wales. This research was carried out in North Wales but might usefully inform practice across Wale

Creating safe places: an exploratory evaluation of a school-based emotional support service

School-based interventions for young people with emotional/mental health problems are often provided by external practitioners and their relationship with host schools is a key influence on implementation. Poor integration within school systems, schools’ tendency to define interventions around pupils’ behaviour and teachers’ control over access, may undermine therapeutic relationships. This study examines how one school-based intervention—Bounceback—addressed these challenges. Methods comprised interviews with programme staff, school staff and service users. Bounceback sought to develop therapeutic relationships through creating a safe, welcoming place and maximising pupils’ choice about how they engaged with it. To ensure Bounceback was delivered as intended, staff developed five conditions which schools were asked to meet: adhering to referral criteria, ensuring that attendance was voluntary, appropriate completion of referral forms, mechanisms for contacting pupils and private accommodation to maintain confidentiality. Pupils reported high levels of acceptability and described relationships of trust with Bounceback staff. Although pupils had choice about most aspects of Bounceback, teachers controlled access to it, partly in order to manage demand. The study highlights the need for external agencies to communicate their aims and needs clearly to schools and the importance of peripatetic practitioners being well integrated within their parent organisations

"Gelli ymddiried ynof i…" Pobl ifanc yn mynd ar goll ac sy'n cael, neu mewn perygl o gael, eu cam-drin drwy gamfanteisio rhywiol yng Ngogledd Cymru'

Barnardo’s mae camfanteisio’n rhywiol ar blant (CSE) wedi bod yn flaenoriaeth strategol, ac yn faes allweddol ar gyfer datblygu arferion am fwy na dau ddegawd. Yng Nghymru, mae Barnardo’s Cymru wedi gweithio’n agos a Llywodraeth Cymru ers 2005 er mwyn cefnogi datblygu polisi cydnerth a chanllawiau arferion er mwyn delio a CSE yng Nghymru. Mae ymchwil sefydledig a thystiolaeth o arferion yn dangos cysylltiad cryf rhwng plant a phobl ifanc sy’n mynd ar goll a’r perygl o wynebu camfanteisio rhywiol. Yn ystod y blynyddoedd diweddar, mae cyfres o erlyniadau proffil uchel mewn perthynas ag achosion o CSE wedi codi ymwybyddiaeth y cyhoedd ynglŷn a’r drosedd hon. Cafodd rhwydweithiau o droseddwyr a fu’n cam-drin plant a phobl ifanc am nifer o flynyddoedd eu datguddio yn Rotherham, Rochdale, Derby, Sheffield, Manceinion a Rhydychen, gan arwain at gynnydd mewn gweithgaredd ar draws pob sector er mwyn gwella diogelwch ac amharu ar dramgwyddwyr. Mae’r ymchwil hwn yn amcanu at wella dealltwriaeth o natur y berthynas rhwng mynd ar goll a CSE, a gwella ymatebion i blant a phobl ifanc sydd mewn perygl. Er bod y mater hwn wedi cael ei ystyried ar lefel y DU, ychydig iawn o ymchwil sydd wedi cael ei wneud yng Nghymru i blant a phobl ifanc sy’n mynd ar goll a’r berthynas rhwng mynd ar goll a’r risg o ddioddef CSE. Cynhaliwyd yr ymchwil hwn yng Ngogledd Cymru, ond gallai fod yn ddefnyddiol fel sail I arferion ar draws Cymru

Darwin, the devil, and the management of transmissible cancers

Modern conservation science frequently relies on genetic tools to manage imperiled populations threatened by processes such as habitat fragmentation and infectious diseases. Translocation of individuals to restore genetic diversity (genetic rescue) is increasingly used to manage vulnerable populations, but it can swamp local adaptations and lead to outbreeding depression. Thus, genetic management is context dependent and needs evaluation across multiple generations . Genomic studies can help evaluate the extent to which populations are locally adapted to assess the costs and benefits of translocations. Predicting the long‐term fitness effects of genetic interventions and their evolutionary consequences is a vital step in managing dwindling populations threatened by emerging infectious diseases

Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.

Neutrophils play a key role in innate immunity. As the dominant circulating phagocyte, they are rapidly recruited from the bloodstream to sites of infection or injury to internalize and destroy microbes. More recently, neutrophils have been identified in uninfected organs, challenging the classical view of their function. Here we show that neutrophils were present in lymph nodes (LNs) in homeostasis. Using flow cytometry and confocal imaging, we identified neutrophils within LNs in naive, unchallenged mice, including LNs draining the skin, lungs, and gastrointestinal tract. Neutrophils were enriched within specific anatomical regions, in the interfollicular zone, a site of T cell activation. Intravital two-photon microscopy demonstrated that LN neutrophils were motile, trafficked into LNs from both blood and tissues via high endothelial venules and afferent lymphatics, respectively, and formed interactions with dendritic cells in LNs. Murine and human LN neutrophils had a distinct phenotype compared with circulating neutrophils, with higher major histocompatibility complex II (MHCII) expression, suggesting a potential role in CD4 T cell activation. Upon ex vivo stimulation with IgG immune complex (IC), neutrophils up-regulated expression of MHCII and costimulatory molecules and increased T cell activation. In vivo, neutrophils were capable of delivering circulating IC to LNs, suggesting a broader functional remit. Overall, our data challenge the perception that neutrophil patrol is limited to the circulation in homeostasis, adding LNs to their routine surveillance territory.L.S.C.L. was funded by Wellcome Trust (104384/Z/14/Z). M.R.C. is supported by National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre, Chan-Zuckerburg Initiative Human Cell Atlas Technology Development Grant, Medical Research Council New Investigator Research Grant (MR/N024907/1), Arthritis Research UK Cure Challenge Research Grant (21777), and NIHR Research Professorship (RP-2017-08- ST2-002)

The ecology and evolution of wildlife cancers: Applications for management and conservation

Evolutionary Applications published by John Wiley & Sons Ltd Ecological and evolutionary concepts have been widely adopted to understand host–pathogen dynamics, and more recently, integrated into wildlife disease management. Cancer is a ubiquitous disease that affects most metazoan species; however, the role of oncogenic phenomena in eco-evolutionary processes and its implications for wildlife management and conservation remains undeveloped. Despite the pervasive nature of cancer across taxa, our ability to detect its occurrence, progression and prevalence in wildlife populations is constrained due to logistic and diagnostic limitations, which suggests that most cancers in the wild are unreported and understudied. Nevertheless, an increasing number of virus-associated and directly transmissible cancers in terrestrial and aquatic environments have been detected. Furthermore, anthropogenic activities and sudden environmental changes are increasingly associated with cancer incidence in wildlife. This highlights the need to upscale surveillance efforts, collection of critical data and developing novel approaches for studying the emergence and evolution of cancers in the wild. Here, we discuss the relevance of malignant cells as important agents of selection and offer a holistic framework to understand the interplay of ecological, epidemiological and evolutionary dynamics of cancer in wildlife. We use a directly transmissible cancer (devil facial tumour disease) as a model system to reveal the potential evolutionary dynamics and broader ecological effects of cancer epidemics in wildlife. We provide further examples of tumour–host interactions and trade-offs that may lead to changes in life histories, and epidemiological and population dynamics. Within this framework, we explore immunological strategies at the individual level as well as transgenerational adaptations at the population level. Then, we highlight the need to integrate multiple disciplines to undertake comparative cancer research at the human–domestic–wildlife interface and their environments. Finally, we suggest strategies for screening cancer incidence in wildlife and discuss how to integrate ecological and evolutionary concepts in the management of current and future cancer epizootics

Effectiveness of Web-Delivered Acceptance and Commitment Therapy in Relation to Mental Health and Well-Being: A Systematic Review and Meta-Analysis

BACKGROUND: The need for effective interventions to improve mental health and emotional well-being at a population level are gaining prominence both in the United Kingdom and globally. Advances in technology and widespread adoption of Internet capable devices have facilitated rapid development of Web-delivered psychological therapies. Interventions designed to manage a range of affective disorders by applying diverse therapeutic approaches are widely available. OBJECTIVE: The main aim of this review was to evaluate the evidence base of acceptance and commitment therapy (ACT) in a Web-based delivery format. METHOD: A systematic review of the literature and meta-analysis was conducted. Two electronic databases were searched for Web-delivered interventions utilizing ACT for the management of affective disorders or well-being. Only Randomized Controlled Trials (RCTs) were included. RESULTS: The search strategy identified 59 articles. Of these, 10 articles met the inclusion criteria specified. The range of conditions and outcome measures that were identified limited the ability to draw firm conclusions about the efficacy of Web-delivered ACT-based intervention for anxiety or well-being. CONCLUSIONS: ACT in a Web-based delivery format was found to be effective in the management of depression. Rates of adherence to study protocols and completion were high overall suggesting that this therapeutic approach is highly acceptable for patients and the general public

Allograft rejection is associated with development of functional IgE specific for donor MHC antigens.

BACKGROUND: Donor-specific antibodies of the IgG isotype are measured routinely for diagnostic purposes in renal transplant recipients and are associated with antibody-mediated rejection and long-term graft loss. OBJECTIVE: This study aimed to investigate whether MHC-specific antibodies of the IgE isotype are induced during allograft rejection. METHODS: Anti-MHC/HLA IgE levels were measured in sera of mice grafted with skin or heart transplants from various donor strains and in sera of kidney transplant patients with high levels of HLA IgG. Mediator release was triggered in vitro by stimulating basophils that were coated with murine or human IgE-positive serum, respectively, with specific recombinant MHC/HLA antigens. Kidney tissue samples obtained from organ donors were analyzed by using flow cytometry for cells expressing the high-affinity receptor for IgE (FcεRI). RESULTS: Donor MHC class I- and MHC class II-specific IgE was found on acute rejection of skin and heart grafts in several murine strain combinations, as well as during chronic antibody-mediated heart graft rejection. Anti-HLA IgE, including donor HLA class I and II specificities, was identified in a group of sensitized transplant recipients. Murine and human anti-MHC/HLA IgE triggered mediator release in coated basophils on stimulation with specific MHC/HLA antigens. HLA-specific IgE was not linked to atopy, and allergen-specific IgE present in allergic patients did not cross-react with HLA antigens. FcεRI+ cells were found in the human renal cortex and medulla and provide targets for HLA-specific IgE. CONCLUSION: These results demonstrate that MHC/HLA-specific IgE develops during an alloresponse and is functional in mediating effector mechanisms

Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world\u27s largest carnivorous marsupial

Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs