A women’s worker in court: A more appropriate service for women defendants with mental health issues?

Aims Court liaison services aim to reduce mental illness in prison through early treatment and/or diversion into care of defendants negotiating their court proceedings. However, liaison services may inadvertently contribute to gender inequalities in mental health in the prison system. This is because women often do not access liaison services. This is attributed to services failing to recognise that women have different needs from men. To address this, it is essential that the needs of women in contact with the criminal justice system (CJS) are clearly articulated. However, there is a dearth of research that considers women’s needs at this stage of their journey through the CJS. This paper aims to identify these needs before women enter prison. It does so through an analysis of a pilot Women’s Support Service based at a Magistrates’ Court, a response to concerns that women were not accessing the local liaison service. Characteristics of women defendants attending the service are described, specifically their home environments, general and mental health needs. Their support needs when in contact with the CJS and the links the service must forge with local community organisations to provide this, are also presented. This knowledge will develop/ tailor existing services available to women defendants to improve their access to these and optimise the benefits they can derive from them. Methods Proformas were completed by a women specialist worker for 86 women defendants assessed in 4 months. Information was collected on characteristics including education, domestic violence, accommodation, physical and mental health.. This specialist worker recorded the range of needs identified by defendants at assessment and the services to which women were referred. Results Access to the Women’s Support Service is high, with only 11.3% of women refusing to use the service. Women attending have high levels of physical and mental health issues. Their mental health issues have not being addressed prior to accessing the service. Women often come from single households and environments high in domestic abuse. Women have multiple needs related to benefits, finance, housing, domestic abuse, education and career guidance. These are more frequent than those that explicitly link to mental health. The women’s worker providing the service referred women to 68 services from a wide variety of statutory and voluntary organisations. Conclusions The Women’s Support Service is accessed by a higher number of women, many more than access the local liaison service. It is suggested that this is due to their multiple and gender specific needs being adequately addressed by the former service and the organisations to whom they are referred. Mental health needs may also be secondary to other more basic needs, that makes the generic service provided but the Women’s support Service more appropriate than a liaison service that deals with mental health support alone

Comparison of the functional and structural characteristics of rare TSC2 variants with clinical and genetic findings

The TSC1 and TSC2 gene products interact to form the tuberous sclerosis complex (TSC), an important negative regulator of the mechanistic target of rapamycin complex 1 (TORC1). Inactivating mutations in TSC1 or TSC2 cause TSC, and the identification of a pathogenic TSC1 or TSC2 variant helps establish a diagnosis of TSC. However, it is not always clear whether TSC1 and TSC2 variants are inactivating. To determine whether TSC1 and TSC2 variants of uncertain clinical significance affect TSC complex function and cause TSC, in vitro assays of TORC1 activity can be employed. Here we combine genetic, functional, and structural approaches to try and classify a series of 15 TSC2 VUS. We investigated the effects of the variants on the formation of the TSC complex, on TORC1 activity and on TSC2 pre-mRNA splicing. In 13 cases (87%), the functional data supported the hypothesis that the identified TSC2 variant caused TSC. Our results illustrate the benefits and limitations of functional testing for TSC

Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Recently it has been shown that missense mutations to the TSC1 gene can cause TSC. Methods: We have used in vitro biochemical assays to investigate the effects on TSC1 function of TSC1 missense variants submitted to the Leiden Open Variation Database. Results: We identified specific substitutions between amino acids 50 and 190 in the N-terminal region of TSC1 that result in reduced steady state levels of the protein and lead to increased mTOR signalling. Conclusion: Our results suggest that amino acid residues within the N-terminal region of TSC1 are important for TSC1 function and for maintaining the activity of the TSC1-TSC2 complex

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations

Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood

Widespread expression of human alpha 1-antitrypsin in transgenic mice revealed by in situ hybridization

In situ hybridization is a powerful means of identifying sites of gene expression. We used this technique to examine the spatial and developmental control of transcription of the human alpha 1-antitrypsin (alpha 1 AT) gene in transgenic mice carrying this gene and extensive 5'- and 3'-flanking sequences. In addition to expression in yolk sac and liver, human alpha 1AT RNA was detected in gut, stomach, pancreas, nasal epithelium, pharynx, bronchi, spinal ganglia, and ossifying cartilage of transgenic fetuses at 14.5 days post coitum (dpc). In transgenic adults, expression was no longer found in the pancreas but was found in the kidney and salivary gland. In each tissue, expression was confined to a specific cell population. This pattern of alpha 1AT expression was found to correlate with that seen in several fetal and adult human tissues. These results suggest a wider role of alpha 1AT in human physiology and development than previously suspected, and they demonstrated the potential value of this approach in delineating the physiological role of human proteins. Expression of the endogenous alpha 1AT gene in mice was confined to a limited, but overlapping, set of tissues, suggesting that the cis-acting DNA sequences that regulate the expression of the human and mouse genes interact differently with transcription factors present in mouse cells