Evaluation of an acute trust Domestic Abuse Coordinator role: Impact findings and a budget impact model.

Domestic Abuse Coordinators (DACs) work strategically across National Health Service (NHS) hospital and other off-site clinical settings to support clinical staff in domestic abuse enquiry and response, and to co-lead the development and implementation of effective clinical policies and procedures for the management of domestic abuse and the support of survivors. Drawing on data from a large NHS acute trust in central London, we analyse the impact of the DAC role in increasing the rate of referrals of high-risk domestic abuse cases, and generate plausible estimates of the budget impact of the DAC role in respect of costs accrued to NHS trusts. Using eight quarters of clinical data and an interrupted time series design, we find that evidence that implementation of a DAC role is linked with an increase in the rate of high-risk referrals of between 18% and 21% per quarter, indicating improved responses to victim-survivors at highest risk of imminent harm. Under a range of reasonable assumptions, initiation of the DAC role is shown to be cost-saving to an employing acute trust. Future work should seek to quantify the direct impacts to survivor health and wellbeing of the implementation of the DAC role.

Long-range repression by ecdysone receptor on complex enhancers of the insulin receptor gene.

The insulin signaling pathway is evolutionarily conserved throughout metazoans, playing key roles in development, growth, and metabolism. Misregulation of this pathway is associated with a multitude of disease states including diabetes, cancer, and neurodegeneration. Genome-wide association studies indicate that natural variants in putative intronic regulatory elements of the human insulin receptor gene ( INSR) are associated with metabolic conditions, however, this gene's transcriptional regulation remains incompletely studied. INSR is widely expressed throughout development and was previously described as a 'housekeeping' gene. Yet, there is abundant evidence that this gene is expressed in a cell-type specific manner, with dynamic regulation in response to environmental signals. The Drosophila insulin-like receptor gene ( InR ) is homologous to the human INSR gene and was previously shown to be regulated by multiple transcriptional elements located primarily within the introns of the gene. These elements were roughly defined in ∼1.5 kbp segments, but we lack an understanding of the potential detailed mechanisms of their regulation, as well as the integrative output of the battery of enhancers in the entire locus. Using luciferase assays, we characterized the substructure of these cis-regulatory elements in Drosophila S2 cells, focusing on regulation through the ecdysone receptor (EcR) and the dFOXO transcription factor. The direct action of EcR on Enhancer 2 reveals a bimodal form of regulation, with active repression in the absence of the ligand, and positive activation in the presence of 20E. By identifying the location of activators of this enhancer, we characterized a long-range of repression acting over at least 475 bp, similar to the action of long-range repressors found in the embryo. dFOXO and 20E have contrasting effects on some of the individual regulatory elements, and for the adjacent enhancers 2 and 3, their influence was/was not found to be additive, indicating that enhancer action on this locus can/cannot be characterized in part by additive models. Other characterized enhancers from within this locus exhibited "distributed" or "localized" modes of action, suggesting that predicting the joint functional output of multiple regulatory regions will require a deeper experimental characterization. The noncoding intronic regions of InR have demonstrated dynamic regulation of expression and cell type specificity. This complex transcriptional circuitry goes beyond the simple conception of a 'housekeeping' gene. Further studies are aimed at identifying how these elements work together in vivo to generate finely tuned expression in tissue- and temporal-specific manners, to provide a guide to understanding the impact of natural variation in this gene's regulation, applicable to human genetic studies.

Long-range repression by ecdysone receptor on complex enhancers of the insulin receptor gene.

The insulin signalling pathway is evolutionarily conserved throughout metazoans, playing key roles in development, growth, and metabolism. Misregulation of this pathway is associated with a multitude of disease states including diabetes, cancer, and neurodegeneration. The human insulin receptor gene (INSR) is widely expressed throughout development and was previously described as a 'housekeeping' gene. Yet, there is abundant evidence that this gene is expressed in a cell-type specific manner, with dynamic regulation in response to environmental signals. The Drosophila insulin-like receptor gene (InR) is homologous to the human INSR gene and was previously shown to be regulated by multiple transcriptional elements located primarily within the introns of the gene. These elements were roughly defined in ~1.5 kbp segments, but we lack an understanding of the potential detailed mechanisms of their regulation. We characterized the substructure of these cis-regulatory elements in Drosophila S2 cells, focusing on regulation through the ecdysone receptor (EcR) and the dFOXO transcription factor. By identifying specific locations of activators and repressors within 300 bp subelements, we show that some previously identified enhancers consist of relatively compact clusters of activators, while others have a distributed architecture not amenable to further reduction. In addition, these assays uncovered a long-range repressive action of unliganded EcR. The complex transcriptional circuitry likely endows InR with a highly flexible and tissue-specific response to tune insulin signalling. Further studies will provide insights to demonstrate the impact of natural variation in this gene's regulation, applicable to human genetic studies.

Identifying demographics of high risk male and LGBTQ+ survivors of domestic abuse from acute London hospital referrals - case review.

BACKGROUND: Heterosexual men, and lesbians, gay men, bisexual, transgender and queer (LGBTQ+) people are under-described in research and resources relating to domestic abuse (DA), compared to heterosexual cisgender female survivors. Many of the identified DA cases within our hospital organisation that warrant onward multidisciplinary referral, due to ongoing high harm risk, are for male and LGBTQ+ survivors. We aimed to describe demographics and risk patterns of these cases, to inform and equip our specialist Independent Domestic Violence Advocacy (IDVA) service. METHOD: We performed a retrospective case-note review of all Multi-Agency Risk Assessment Conferences (MARAC) referrals for DA, featuring male & LGBTQ+ subjects, across Chelsea and Westminster Hospital NHS Foundation Trust (CWFT), London, UK between April 2019 - December 2020. We recorded demographic data of referral subjects and perpetrators; the origin of referral; the nature of the initial presenting complaint and whether the DA was identified by the subject or by the healthcare provider on enquiry; and recorded rates of co-marginalising and harm risk factors (dependent children, disability, mental health comorbidity, HIV status, drug use, homelessness). RESULTS: We identified 33 cases: 10.2% of CWFT's total MARAC referrals were for men, and 6.7% for LGBTQ+ people (cf. national figures from the same period: 0.1% and 1.3% respectively). Nearly half (48.5%, 16) of the referrals came from sexual health services, just under half (45.5%, 15) from Emergency Departments. 42% (14) disclosures were elicited incidentally during routine enquiry. Six (18%) subjects were also known survivors of sexual violence in addition to DA. The majority (79%, 26) of perpetrators were current or ex-intimate partners. Eight (24%) of the subjects had children under 18. High rates of co-marginalisation factors were present, including use of recreational drugs (45.5%, 15), belonging to an ethnic minority (39.4%, 13), living with HIV (24.2%, 8), living with a disability (18%, 6), mental health comorbidity (27.3%, 9), and experience or risk of homelessness (9%, 3). CONCLUSIONS: Our trust reports a high rate of male and LGBTQ+ high-risk DA referrals, and amongst these there is a high rate of intersecting disadvantages and risk factors. This underlines a need for inclusivity for marginalised groups, inbuilt into domestic abuse health responses. The high rate of disclosure during routine enquiry for domestic abuse supports the use of DA routine enquiry in sexual health settings, and points towards the utility of selective enquiry in other settings (for example, heterosexual males presenting with injuries to emergency departments). We hope that by working with a specialised LGBTQ+ IDVA, we will improve both prompt identification and better outcomes for more GSM patients.

KIR3DL05 and KIR3DS02 Recognition of a Nonclassical MHC Class I Molecule in the Rhesus Macaque Implicated in Pregnancy Success.

Knowledge of the MHC class I ligands of rhesus macaque killer-cell Ig-like receptors (KIRs) is fundamental to understanding the role of natural killer (NK) cells in this species as a nonhuman primate model for infectious diseases, transplantation and reproductive biology. We previously identified Mamu-AG as a ligand for KIR3DL05. Mamu-AG is a nonclassical MHC class I molecule that is expressed at the maternal-fetal interface of the placenta in rhesus macaques similar to HLA-G in humans. Although Mamu-AG and HLA-G share similar molecular features, including limited polymorphism and a short cytoplasmic tail, Mamu-AG is considerably more polymorphic. To determine which allotypes of Mamu-AG serve as ligands for KIR3DL05, we tested reporter cell lines expressing five different alleles of KIR3DL05 (KIR3DL05*001, KIR3DL05*004, KIR3DL05*005, KIR3DL05*008 and KIR3DL05*X) for responses to target cells expressing eight different alleles of Mamu-AG. All five allotypes of KIR3DL05 responded to Mamu-AG2*01:01, two exhibited dominant responses to Mamu-AG1*05:01, and three had low but detectable responses to Mamu-AG3*03:01, -AG3*03:02, -AG3*03:03 and -AG3*03:04. Since KIR3DL05*X is the product of recombination between KIR3DL05 and KIR3DS02, we also tested an allotype of KIR3DS02 (KIR3DS02*004) and found that this activating KIR also recognizes Mamu-AG2*01:01. Additional analysis of Mamu-AG variants with single amino acid substitutions identified residues in the α1-domain essential for recognition by KIR3DL05. These results reveal variation in KIR3DL05 and KIR3DS02 responses to Mamu-AG and define Mamu-AG polymorphisms that differentially affect KIR recognition.

Outcomes of domestic violence screening at an acute London trust: are there missed opportunities for intervention?

OBJECTIVES: Domestic violence screening is advocated in some healthcare settings. Evidence that it increases referral to support agencies or improves health outcomes is limited. This study aimed to (1) investigate the proportion of hospital patients reporting domestic violence, (2) describe characteristics and previous hospital attendances of affected patients and (3) assess referrals to an in-house domestic violence advisor from Camden Safety Net. DESIGN: A series of observational studies. SETTING: Three outpatient clinics at the Royal Free London NHS Foundation Trust. PARTICIPANTS: 10,158 patients screened for domestic violence in community gynaecology, genitourinary medicine (GUM) and HIV medicine clinics between 1 October 2013 and 30 June 2014. Also 2253 Camden Safety Net referrals over the same period. MAIN OUTCOME MEASURES: (1) Percentage reporting domestic violence by age group gender, ethnicity and clinic. (2) Rates of hospital attendances in the past 3 years for those screening positive and negative. (3) Characteristics, uptake and risk assessment results for hospital in-house domestic violence referrals compared with Camden Safety Net referrals from other sources. RESULTS: Of the 10,158 patients screened, 57.4% were female with a median age of 30 years. Overall, 7.1% reported ever-experiencing domestic violence, ranging from 5.7% in GUM to 29.4% in HIV services. People screening positive for domestic violence had higher rates of previous emergency department attendances (rate ratio (RR) 1.63, 95% CI 1.09 to 2.48), emergency inpatient admissions (RR 2.27, 95% CI 1.37 to 3.84) and day-case admissions (RR 2.03, 95% CI 1.23 to 3.43) than those screening negative. The 77 hospital referrals to the hospital-based domestic violence advisor during the study period were more likely to be taken up and to be classified as high risk than referrals from elsewhere. CONCLUSIONS: Selective screening for domestic violence in high-risk hospital clinic populations has the potential to identify affected patients and promote good uptake of referrals for in-house domestic violence support.