Support or justice: a triangulated multi-focal view of sexual assault victim support in a UK sexual assault referral centre (SARC).

BACKGROUND: Despite vast levels of underreporting, sexual assault remains an issue at scale in the UK, necessitating the presence of statutory and voluntary organisations in the support of victims. Understanding the experiences of all parties within this context is important for the resilience of support that can be provided at a systems level. This study examines the barriers faced by service providers when working with victims of sexual assault. METHODS: Semi-structured interviews took place with eleven professionals working in or in conjunction with a Sexual Assault Referral Centre (SARC) in Southeast England, which were subsequently analysed using inductive thematic analysis. RESULTS: Five themes were identified exploring SARC staff's experiences with (i) communication breakdowns with external services; (ii) delivering support in an underfunded system; (iii) tailoring support to survivors' needs; (iv) the Criminal Justice System fails victims of sexual assault; and (v) reckoning with burnouts and vicarious trauma. CONCLUSION: Significant gaps in UK service provision for sexual assault victims are identified, particularly within the criminal justice system, where legal and investigative processes are cited as retraumatizing. The results emphasize the urgency of enhanced training, coordination, resources, and trauma-informed practices across organizations to better serve victims and support overwhelmed providers. Prioritizing systemic improvements is crucial to address the complex needs of both victims and service professionals.

Bioanalytical Approaches to Support the Development of Antibody-Oligonucleotide Conjugate (AOC) Therapeutic Proteins.

RNA interference (RNAi) is a biological process that evolved to protect eukaryotic organisms from foreign genes delivered by viruses. This process has been adapted as a powerful tool to treat numerous diseases through the delivery of small-interfering RNAs (siRNAs) to target cells to alter aberrant gene expression.Antibody-oligonucleotide conjugates (AOCs) are monoclonal antibodies with complexed siRNA or antisense oligonucleotides (ASOs) that have emerged to address some of the challenges faced by naked or chemically conjugated siRNA, which include rapid clearance from systemic circulation and lack of selective delivery of siRNA to target cells.It is essential to characterize the ADME properties of an AOC during development to optimize distribution to target tissues, to minimize the impact of biotransformation on exposure, and to characterize the PK/PD relationship to guide translation. However, owing to the complexity of AOC structure, this presents significant bioanalytical challenges, and multiple bioanalytical measurements are required to investigate the pharmacokinetics and biotransformation of the antibody, linker, and siRNA payload.In this paper, we describe an analytical workflow that details in vivo characterization of AOCs through measurement of their distinct molecular components to provide the basis for greater understanding of their ADME properties. Although the approaches herein can be applied to in vitro characterization of AOCs, this paper will focus on in vivo applications. This workflow relies on high-resolution mass spectrometry as the principal means of detection and leverages chromatographic, affinity-based, and enzymatic sample preparation steps.

Reducing target binding affinity improves the therapeutic index of anti-MET antibody-drug conjugate in tumor bearing animals.

Many oncology antibody-drug conjugates (ADCs) have failed to demonstrate efficacy in clinic because of dose-limiting toxicity caused by uptake into healthy tissues. We developed an approach that harnesses ADC affinity to broaden the therapeutic index (TI) using two anti-mesenchymal-epithelial transition factor (MET) monoclonal antibodies (mAbs) with high affinity (HAV) or low affinity (LAV) conjugated to monomethyl auristatin E (MMAE). The estimated TI for LAV-ADC was at least 3 times greater than the HAV-ADC. The LAV- and HAV-ADCs showed similar levels of anti-tumor activity in the xenograft model, while the 111In-DTPA studies showed similar amounts of the ADCs in HT29 tumors. Although the LAV-ADC has ~2-fold slower blood clearance than the HAV-ADC, higher liver toxicity was observed with HAV-ADC. While the SPECT/CT 111In- and 124I- DTPA findings showed HAV-ADC has higher accumulation and rapid clearance in normal tissues, intravital microscopy (IVM) studies confirmed HAV mAb accumulates within hepatic sinusoidal endothelial cells while the LAV mAb does not. These results demonstrated that lowering the MET binding affinity provides a larger TI for MET-ADC. Decreasing the affinity of the ADC reduces the target mediated drug disposition (TMDD) to MET expressed in normal tissues while maintaining uptake/delivery to the tumor. This approach can be applied to multiple ADCs to improve the clinical outcomes.

Prevalence of adverse childhood experiences and their cumulative impact associated lifetime health outcomes in the Emirate of Abu-Dhabi, United Arab Emirates.

BACKGROUND: Adverse Childhood Experiences have been associated with poor health outcomes later in life. OBJECTIVE: The objective of the study was to determine the relationship between cumulative ACEs, risky health behaviors, chronic diseases, and mental health among a large-scale sample from the Emirate of Abu Dhabi. PARTICIPANTS AND SETTING: A retrospective cross-sectional study was performed with 922 participants over the age of 18, living in Abu Dhabi. METHODS: The Adverse Childhood Experiences International Questionnaire (ACE-IQ) was used to assess ACEs, alongside a survey of adult health outcomes, mental health outcomes, and risk-taking behaviors. RESULTS: Logistic regression models examined the association between retrospective ACEs and these outcomes. The respondents reported an average of 1.74 ACEs. The most prevalent ACEs were household violence, parental death or divorce, and community violence. The accumulation of ACEs significantly predicts increases in the risk of a variety of adult-onset health morbidities, all measured mental health morbidities, and all measured risk-taking behaviors, with evidence of thresholds of ACE accumulation dictating risk. CONCLUSIONS: The baseline presence of ACEs among this Abu Dhabi sample, along with the associated risks of physical and mental health morbidities, and risk-taking behaviors play a significant role in understanding the extent, nature, and associated sequalae of ACEs in this population; providing nuanced context for early intervention. Our findings will inform the planning and implementation of specific prevention and awareness raising programs while promoting safe environments where children are healthy and can thrive.

Learning from Power Signals: An Automated Approach to Electrical Disturbance Identification within a Power Transmission System.

As power quality becomes a higher priority in the electric utility industry, the amount of disturbance event data continues to grow. Utilities do not have the required personnel to analyze each event by hand. This work presents an automated approach for analyzing power quality events recorded by digital fault recorders and power quality monitors operating within a power transmission system. The automated approach leverages rule-based analytics to examine the time and frequency domain characteristics of the voltage and current signals. Customizable thresholds are set to categorize each disturbance event. The events analyzed within this work include various faults, motor starting, and incipient instrument transformer failure. Analytics for fourteen different event types have been developed. The analytics were tested on 160 signal files and yielded an average accuracy of 99%. Continuous nominal signal data analysis was performed using an approach called the cyclic histogram. The cyclic histogram process is intended to be integrated into the digital fault recorders themselves in order to facilitate the detection of subtle signal variations that are too small to trigger a disturbance event and that can occur over hours or days. In addition to reducing memory requirements by a factor of 320, it is anticipated that cyclic histogram processing will aid in identifying incipient events and identifiers. This project is expected to save engineers time by automating the classification of disturbance events and increasing the reliability of the transmission system by providing near real-time detection and identification of disturbances as well as prevention of problems before they occur.

Individual Effects of Alkali Element and Wire Structure on Metal Transfer Process in Argon Metal-Cored Arc Welding.

This study aimed to clarify the effect of wire structure and alkaline elements in wire composition on metal transfer behavior in metal-cored arc welding (MCAW). A comparison of metal transfer in pure argon gas was carried out using a solid wire (wire 1), a metal-cored wire without an alkaline element (wire 2), and another metal-cored wire with 0.084 mass% of sodium (wire 3). The experiments were conducted under 280 and 320 A welding currents, observed by high-speed imaging techniques equipped with laser assistance and bandpass filters. At 280 A, wire 1 showed a streaming transfer mode, while the others showed a projected one. When the current was 320 A, the metal transfer of wire 2 changed to streaming, while wire 3 remained projected. As sodium has a lower ionization energy than iron, the mixing of sodium vapor into the iron plasma increases its electrical conductivity, raising the proportion of current flowing through metal vapor plasma. As a result, the current flows to the upper region of the molten metal on the wire tip, with the resulting electromagnetic force causing droplet detachment. Consequently, the metal transfer mode in wire 3 remained projected. Furthermore, weld bead formation is the best for wire 3.

A Qualitative Investigation of Service Providers' Experiences Supporting Raped and Sexually Abused Men.

Substantial gaps remain in our understanding of the risks and barriers that exist for men affected by rape and sexual abuse. The present research utilized semi-structured interviews with 12 service providers from specialist organizations in the United Kingdom. An interpretative phenomenological analysis revealed three superordinate themes: (a) survivors' needs for agency, safety, and control as functions of their masculinity; (b) the impact of rape myths and their challenge to therapeutic intervention; and (c) survivors' expectations around reporting and the police. The role of masculinity and social stigma permeated participants' accounts, with negative stereotypes and male rape myths influencing reporting, access to services, and survivors' coping mechanisms. Results are discussed in relation to current service provision within the United Kingdom, and avenues for improvement are suggested.

Online Symptom Monitoring During Pelvic Radiation Therapy: Randomized Pilot Trial of the eRAPID Intervention.

PURPOSE: Radiation therapy (RT) and chemoRT for pelvic cancers increase survival but are associated with serious treatment-related symptoms. Electronic-patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) is a secure online system for patients to self-report symptoms, generating immediate advice for hospital contact or self-management. This pilot study aimed to establish feasibility and acceptability of the system. METHODS AND MATERIALS: In a prospective 2-center randomized parallel-group pilot study, patients undergoing radical pelvic RT for prostate cancer (prostateRT) or chemoRT for lower gastrointestinal and gynecological cancers were randomized to usual care (UC) or eRAPID (weekly online symptom reporting for 12, 18, and 24 weeks). Primary outcomes were recruitment/attrition, study completion, and patient adherence. Secondary outcomes were effect on hospital services and performance of patient outcome measures. Missing data, floor/ceiling effects, and mean change scores were examined for Functional Assessment of Cancer Therapy (FACT-G), European Organisation for Research and Treatment of Cancer, Quality of Life (EORTC QLQ C-30), self-efficacy, and EuroQol (EQ5D). RESULTS: From 228 patients approached, 167 (73.2%) were consented and randomized (83, eRAPID; 84, UC; 87, prostateRT; 80, chemoRT); 150 of 167 completed 24 study weeks. Only 16 patients (9.6%) withdrew (10, eRAPID; 6, UC). In the eRAPID arm, completion rates were higher in patients treated with prostateRT compared with chemoRT (week 1, 93% vs 69%; week 2, 93% vs 68%; week 12, 69% vs 55%). Overall, over 50% of online reports triggered self-management advice for milder adverse events. Unscheduled hospital contact was low, with no difference between eRAPID and UC. Return rates for outcome measures were excellent in prostateRT (97%-91%; 6-24 weeks) but lower in chemoRT (95%-55%; 6-24 weeks). Missing data were low (1%-4.1%), ceiling effects were evident in EQ5D-5L, self-efficacy-scale, and FACT-Physical Wellbeing. At 6 weeks, the chemoRT-eRAPID group showed less deterioration in FACT-G, EORTC QLQ-C30, and EQ5D-Visual Analogue Scale than UC, after baseline adjustment. CONCLUSIONS: eRAPID was successfully added to UC at 2 cancer centers in different patient populations. Acceptability and feasibility were confirmed with excellent adherence by prostate patients, but lower by those undergoing chemoRT for gynecological cancers.

Therapeutic Targeting of Alternative Splicing: A New Frontier in Cancer Treatment.

The ability for cells to harness alternative splicing enables them to diversify their proteome in order to carry out complex biological functions and adapt to external and internal stimuli. The spliceosome is the multiprotein-RNA complex charged with the intricate task of alternative splicing. Aberrant splicing can arise from abnormal spliceosomes or splicing factors and drive cancer development and progression. This review will provide an overview of the alternative splicing process and aberrant splicing in cancer, with a focus on serine/arginine-rich (SR) proteins and their recently reported roles in cancer development and progression and beyond. Recent mapping of the spliceosome, its associated splicing factors, and their relationship to cancer have opened the door to novel therapeutic approaches that capitalize on the widespread influence of alternative splicing. We conclude by discussing small molecule inhibitors of the spliceosome that have been identified in an evolving era of cancer treatment.

Lessons learned from the COVID-19 pandemic and its impact on bioanalysis and drug development.

The COVID-19 pandemic challenged pharmaceutical and bioanalytical communities at large, in the development of vaccines and therapeutics as well as supporting ongoing drug development efforts. Existing processes were challenged to manage loss of staffing at facilities along with added workloads for COVID-19-related study support including conducting preclinical testing, initiating clinical trials, conducting bioanalysis and interactions with regulatory agencies, all in an ultra-rapid timeframes. A key factor of success was creative rethinking of processes and removing barriers - some of which hitherto had been considered immovable. This article describes how bioanalysis was crippled at the onset of the pandemic but how innovative and highly collaborative efforts across teams within and outside of both pharma, bioanalytical labs and regulatory agencies worked together remarkably well.

Development and validation of the Male Rape Myth Acceptance Scale (MRMAS).

Despite growing recognition of male-on-male rape and its related myths, research in this area has been held back by the lack of a reliable and comprehensive measure or scale. The present work utilises a large and diverse participant sample over two studies (Study 1 N = 510, Study 2 N = 527) to validate a new Male Rape Myth Acceptance Scale (MRMAS), measuring myths falling under six principle themes: masculinity, sexuality, pleasure, perpetrators, context, and effect. Analysis suggested a two-factor scale, with 'Blame' and 'Minimisation/Exoneration' sub-scales. Both the overall scale and sub-scales demonstrate excellent reliability and construct validity, and are thus proposed as tools to enable the proliferation of future research on male rape myth acceptance, both in general and specialist populations, in an attempt to improve the experiences of male rape victims.

Induction of NUPR1 and AP­1 contributes to the carcinogenic potential of nickel.

Nickel (Ni) is carcinogenic to humans, and causes cancers of the lung, nasal cavity, and paranasal sinuses. The primary mechanisms of Ni­mediated carcinogenesis involve the epigenetic reprogramming of cells and the ability for Ni to mimic hypoxia. However, the exact mechanisms of carcinogenesis related to Ni are obscure. Nuclear protein 1 (NUPR1) is a stress­response gene overexpressed in cancers, and is capable of conferring chemotherapeutic resistance. Likewise, activator protein 1 (AP­1) is highly responsive to environmental signals, and has been associated with cancer development. In this study, NUPR1 was found to be rapidly and highly induced in human bronchial epithelial (BEAS­2B) cells exposed to Ni, and was overexpressed in Ni­transformed BEAS­2B cells. Similarly, AP­1 subunits, JUN and FOS, were induced in BEAS­2B cells following Ni exposure. Knockdown of JUN or FOS was found to significantly suppress NUPR1 induction following Ni exposure, demonstrating their importance in NUPR1 transactivation. Reactive oxygen species (ROS) are known to induce AP­1, and Ni has been shown to produce ROS. Treatment of BEAS­2B cells with antioxidants was unable to prevent NUPR1 induction by Ni, suggesting that NUPR1 induction by Ni relies on mechanisms other than oxidative stress. To determine how NUPR1 is transcriptionally regulated following Ni exposure, the NUPR1 promoter was cloned and inserted into a luciferase gene reporter vector. Multiple JUN binding sites reside within the NUPR1 promoter, and upon deleting a JUN binding site in the upstream most region within the NUPR1 promoter using site­directed mutagenesis, NUPR1 promoter activity was significantly reduced. This suggests that AP­1 transcriptionally regulates NUPR1. Moreover, knockdown of NUPR1 significantly reduced colony formation and anchorage­independent growth in Ni­transformed BEAS­2B cells. Therefore, these results collectively demonstrate a novel mechanism of NUPR1 induction following Ni exposure, and provide a molecular basis by which NUPR1 may contribute to lung carcinogenesis.

Application of Plasma-Printed Paper-Based SERS Substrate for Cocaine Detection.

Surface-enhanced Raman spectroscopy (SERS) technology is an attractive method for the prompt and accurate on-site screening of illicit drugs. As portable Raman systems are available for on-site screening, the readiness of SERS technology for sensing applications is predominantly dependent on the accuracy, stability and cost-effectiveness of the SERS strip. An atmospheric-pressure plasma-assisted chemical deposition process that can deposit an even distribution of nanogold particles in a one-step process has been developed. The process was used to print a nanogold film on a paper-based substrate using a HAuCl4 solution precursor. X-ray photoelectron spectroscopy (XPS) analysis demonstrates that the gold has been fully reduced and that subsequent plasma post-treatment decreases the carbon content of the film. Results for cocaine detection using this substrate were compared with two commercial SERS substrates, one based on nanogold on paper and the currently available best commercial SERS substrate based on an Ag pillar structure. A larger number of bands associated with cocaine was detected using the plasma-printed substrate than the commercial substrates across a range of cocaine concentrations from 1 to 5000 ng/mL. A detection limit as low as 1 ng/mL cocaine with high spatial uniformity was demonstrated with the plasma-printed substrate. It is shown that the plasma-printed substrate can be produced at a much lower cost than the price of the commercial substrate.

Downregulation of hedgehog-interacting protein (HHIP) contributes to hexavalent chromium-induced malignant transformation of human bronchial epithelial cells.

Hexavalent chromium [Cr(VI)] is a potent human lung carcinogen. Multiple mechanisms have been proposed that contribute to Cr(VI)-induced lung carcinogenesis including oxidative stress, DNA damage, genomic instability and epigenetic modulation. However, the molecular mechanisms and pathways mediating Cr(VI) carcinogenicity have not been fully elucidated. Hedgehog (Hh) signaling is a key pathway that plays important roles in the formation of multiple tissues during embryogenesis and in the maintenance of stem cell populations in adults. Dysregulation of Hh signaling pathway has been reported in many human cancers. Here, we report a drastic reduction in both mRNA and protein levels of hedgehog-interacting protein (HHIP), a downstream target and a negative regulator of Hh signaling, in Cr(VI)-transformed cells. These findings point to a potential role of Hh signaling in Cr(VI)-induced malignant transformation and lung carcinogenesis. Cr(VI)-transformed cells exhibited DNA hypermethylation and silencing histone marks in the promoter region of HHIP, indicating that an epigenetic mechanism mediates Cr(VI)-induced silencing of HHIP. In addition, the major targets of Hh signaling (GLI1-3 and PTCH1) were significantly increased in Cr(VI)-transformed cells, suggesting an aberrant activation of Hh signaling in these cells. Moreover, ectopically expressing HHIP not only suppressed Hh signaling but also inhibited cell proliferation and anchorage-independent growth in Cr(VI)-transformed cells. In conclusion, these findings establish a novel regulatory mechanism underlying Cr(VI)-induced lung carcinogenesis and provide new insights for developing a better diagnostic and prognostic strategy for Cr(VI)-related human lung cancer.

Lipiodol flush under ultrasound guidance in Australia.

BACKGROUND: Lipiodol tubal flushing is offered to select subfertile women primarily to confirm tubal patency and to increase pregnancy rates. AIMS: To investigate the safety of hystero-salpingo contrast sonography (HyCoSy) using Lipiodol flush (through frequency of adverse events and mean recalled pain score) and secondarily to quantify pregnancy rates. MATERIALS AND METHODS: Retrospective observational Phase 1 study of subfertile women in three centres across Australia between June 2017 and June 2019. Cases were identified from medical records, and women telephoned to assess adverse outcomes, procedure tolerability and confirm pregnancy outcomes within six months from procedure. RESULTS: A total of 325 cases were identified; 14 were excluded due to incomplete or abandoned procedure, 32 were lost to follow-up, leaving 279 for analysis. Fourteen women (5% overall) experienced mild vasovagal reactions, with one case of infection and no reports of anaphylaxis or allergy. There were 141 conceptions reported (51%) within six months after Lipiodol flush, and an ongoing pregnancy in 43% (119) of women. For women with ongoing pregnancies, 55% (78/119) conceived spontaneously, and 45% (63/119) via artificial reproductive technology. Mean recalled pain score was 5.7 (SD 3.2; range 0-10) at a single site. CONCLUSIONS: This Phase 1 study has indicated that Lipiodol flush using HyCoSy may be a safe and efficacious alternative to hysterosalpingography in the workup for infertility. The low adverse effect profile observed in this study coupled with a substantial ongoing pregnancy rate indicates that further investigation of Lipiodol under HyCoSy is warranted.

Arsenic Methyltransferase and Methylation of Inorganic Arsenic.

Arsenic occurs naturally in the environment, and exists predominantly as inorganic arsenite (As (III) and arsenate As (V)). Arsenic contamination of drinking water has long been recognized as a major global health concern. Arsenic exposure causes changes in skin color and lesions, and more severe health conditions such as black foot disease as well as various cancers originating in the lungs, skin, and bladder. In order to efficiently metabolize and excrete arsenic, it is methylated to monomethylarsonic and dimethylarsinic acid. One single enzyme, arsenic methyltransferase (AS3MT) is responsible for generating both metabolites. AS3MT has been purified from several mammalian and nonmammalian species, and its mRNA sequences were determined from amino acid sequences. With the advent of genome technology, mRNA sequences of AS3MT have been predicted from many species throughout the animal kingdom. Horizontal gene transfer had been postulated for this gene through phylogenetic studies, which suggests the importance of this gene in appropriately handling arsenic exposures in various organisms. An altered ability to methylate arsenic is dependent on specific single nucleotide polymorphisms (SNPs) in AS3MT. Reduced AS3MT activity resulting in poor metabolism of iAs has been shown to reduce expression of the tumor suppressor gene, p16, which is a potential pathway in arsenic carcinogenesis. Arsenic is also known to induce oxidative stress in cells. However, the presence of antioxidant response elements (AREs) in the promoter sequences of AS3MT in several species does not correlate with the ability to methylate arsenic. ARE elements are known to bind NRF2 and induce antioxidant enzymes to combat oxidative stress. NRF2 may be partly responsible for the biotransformation of iAs and the generation of methylated arsenic species via AS3MT. In this article, arsenic metabolism, excretion, and toxicity, a discussion of the AS3MT gene and its evolutionary history, and DNA methylation resulting from arsenic exposure have been reviewed.

Nuclear protein 1 imparts oncogenic potential and chemotherapeutic resistance in cancer.

Nuclear protein 1 (NUPR1) also known as p8 and candidate of metastasis 1 (COM1) functions as a transcriptional regulator, and plays a role in cell cycle, DNA damage response, apoptosis, autophagy, and chromatin remodeling in response to various cellular stressors. Since it was first suggested to contribute to cancer development and progression in 1999, a number of studies have sought to reveal its function. However, NUPR1 and its biological relevance in cancer have proven difficult to pinpoint. Based on evidence of NUPR1 expression in cancers, its function extends from carcinogenesis and tumorigenesis to metastasis and chemotherapeutic resistance. A tumor suppressive function of NUPR1 has also been documented in multiple cancers. By and large, literature involving NUPR1 and cancer is confined to pancreatic and breast cancers, yet significant progress has been made with respect to NUPR1 expression and its function in lung, colorectal, blood, and prostate cancers, among others. Recent evidence strongly supports the notion that NUPR1 is key in chemotherapeutic resistance by mediating both anti-apoptotic activity and autophagy when challenged with anti-cancer compounds. Therefore, it is of significant importance to understand the broad range of molecular functions directed by NUPR1. In this review, NUPR1 expression and its role in breast, lung, and colorectal cancer development and progression will be addressed.

Numerical Simulation of the Behavior of Hydrogen Source in a Novel Welding Process to Reduce Diffusible Hydrogen.

This study aims to reduce the diffusible hydrogen content in deposited metal during gas metal arc welding (GMAW) and flux-cored arc welding (FCAW) which induces cold cracking. To achieve this, a novel welding torch with a dual gas nozzle has been developed. This special welding torch decreases the hydrogen source gas evaporated from a welding wire by the suction from the inner gas nozzle. In order to improve the suction efficiency of this evaporated gas, precise control of the suction gas flow is indispensable. In this paper, a simplified numerical simulation model of this process has been described. This model can take account of the evaporation of the hydrogen source gas from the wire while simulating the behavior of the shielding gas and the arc. Using this model, the effect of suction nozzle structure and torch operating conditions on suction gas flow pattern and suction efficiency was also investigated to understand the process mechanism. Furthermore, the diffusible hydrogen content in deposited metal was measured by chromatography as a validation step. Results show that some of the shielding gas introduced from a shielding nozzle was drawn inward and also branched into an upward flow that was sucked into the suction nozzle and a downward flow to a base metal. This branching height was defined as the suction limit height, which decisively governed the suction efficiency. As a result, in order to reduce the diffusible hydrogen, it was suggested that the suction limit height should be controlled towards below the wire position, where the evaporation rate of the hydrogen source gas peaks through optimization of the suction nozzle design and the torch operating conditions.

The use of positive behaviour support plans in mental health inpatient care: A mixed methods study.

WHAT IS KNOWN ON THE SUBJECT?: There is a drive to use positive and proactive approaches to mental health care to reduce the use of restrictive practices such as seclusion and restraint. Positive behaviour support plans have been used successfully to do this in learning disability services, and in England, it is now a regulatory requirement that anyone with challenging behaviour should have an individualized behaviour support plan. However, positive behaviour support plans specifically have not been evaluated as part of routine mental health care and mental health nurses' and relatives' attitudes towards them are unknown. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This evaluation of positive behaviour support plans in routine mental health inpatient care found that they had not been widely implemented or completed as intended. Barriers to the use of the plans included confusion among nurses and relatives around the principles of positive behaviour support, including how, when and for whom the plans should be used, difficulties in being able to describe the function of a patient's behaviour and lack of engagement with relatives and patients. Nevertheless, nurses and relatives valued the plans, in particular for their potential to facilitate holistic care. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: To use the plans successfully, mental health nurses will need training to understand fully the rationale behind the positive behaviour support approach and will need to engage more with relatives and patients. Commitment to the approach from the whole care team and organization will be needed to implement the plans consistently for all patients. Abstract Introduction An international drive is to minimize restrictive practices in mental health care. Positive behaviour support plans (PBSPs) help staff prevent behaviour which would require restrictive intervention. Originating in learning disability services, data within mental health care are limited. Aims To evaluate PBSPs within a mental health inpatient service; understand mental health nurses' and relatives' attitudes to them; and understand the barriers and facilitators for their use in routine mental health care. Methods Mixed methods-quality ratings and interviews with relatives and nurses. Results Positive behaviour support plans were poorly implemented. Relatives and nurses valued the potential of PBSPs to facilitate holistic care, though no relative had contributed to one and not every eligible patient had one. Barriers to their use included confusion around positive behaviour support, including how, when and for whom PBSPs should be used, and difficulties describing the function of a behaviour. Discussion The potential of PBSPs to improve mental health care is recognized. However, there are barriers to their use which should be addressed to ensure that PBSPs have been properly implemented before their impact on patient care can be assessed. Implications for practice Mental health professionals implementing PBSPs should engage with relatives and patients, gain organizational commitment and ensure that those involved understand fully the positive behaviour support approach.

Molecular and epigenetic mechanisms of Cr(VI)-induced carcinogenesis.

Chromium (Cr) is a naturally occurring metallic element found in the Earth's crust. While trivalent chromium ([Cr(III)] is considered non-carcinogenic, hexavalent chromium [Cr(VI)] has long been established as an IARC class I human carcinogen, known to induce cancers of the lung. Current literature suggests that Cr(VI) is capable of inducing carcinogenesis through both genetic and epigenetic mechanisms. Although much has been learned about the molecular etiology of Cr(VI)-induced lung carcinogenesis, more remains to be explored. In particular, the explicit epigenetic alterations induced by Cr(VI) in lung cancer including histone modifications and miRNAs, remain understudied. Through comprehensive review of available literature found between 1973 and 2019, this article provides a summary of updated understanding of the molecular mechanisms of Cr(VI)-carcinogenesis. In addition, this review identifies potential research gaps in the areas of histone modifications and miRNAs, which may prompt new niches for future research.