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Abstract Background Eight‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses. Hypothesis We hypothesized that 8‐OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8‐OHdG will be higher in CSF compared with serum from NAD/DM horses. Animals Fifty client‐owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November 2010 and March 2022. Methods Case‐control study using biobanked samples was performed and commercial competitive ELISA kit (Highly Sensitive 8‐OHdG Check ELISA) utilized. Concentration of 8‐OHdG was quantitated in both CSF and serum and compared between groups. Results No correlation was established between the measures of 8‐OHdG in serum and CSF and group. CSF median [8‐OHdG] for NAD/DM was 169.9 pg/mL (IQR25‐75: 67.18‐210.6), CVSM 157.1 pg/mL (IQR25‐75: 132.1‐229.1), EPM 131.4 pg/mL (IQR25‐75: 102.1‐193.2), and control 149.8 pg/mL (IQR25‐75: 113.3‐196.4). Serum median [8‐OHdG] for NAD/DM was 130 pg/mL (IQR25‐75: 51.73‐157.2), CVSM 125.8 pg/mL (IQR25‐75: 62.8‐170.8), EPM 120.6 pg/mL (IQR25‐75: 87.23‐229.7), and control 157.6 pg/mL (IQR25‐75: 97.15‐245.6). Poisson regression analysis showed no difference established once confounding variables were considered. Conclusions Eight‐OHdG did not aid in antemortem diagnosis of NAD/DM in this cohort of horses. At the time of diagnosis horses with NAD/DM do not have ongoing oxidative stress.

Background Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.Methods We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed.Results We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy.Conclusions This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect.Trial registration number ACTRN12613000198729.

Abstract Background Alopecia describes a group of dermatological conditions characterised by hair loss, which are either non‐scarring or scarring in nature, and range from bald patches to complete body hair loss, to general thinning. In the UK, the General Practitioner (GP) is typically the first point of contact, and some patients are referred for specialist dermatology consultation. However, little is known about how individuals with alopecia in the UK experience the care provided by the National Health Service. Objectives We aimed to understand patients' perceptions of primary healthcare and dermatology provision. Further, we aimed to investigate how care provision and patients' overall patient journey might be improved in the UK, and how these lessons may apply internationally. Methods An online mixed methods survey was distributed by Alopecia UK to UK‐based individuals with alopecia. Open‐ended text responses were analysed using qualitative content analysis. Quantitative data were analysed using descriptive analyses and dependent measures t‐tests. Results A total of 291 participants completed the survey. They reported neutral‐to‐partial dissatisfaction with their GP appointments, with greater satisfaction in their most recent compared to their first appointment. Participants highlighted positive experiences with GPs and dermatologists as well as areas for improvement. Participants also expressed a desire for a greater degree of support and understanding about the psychological impact of alopecia. Conclusions Results highlight the importance of being empathic and caring healthcare professionals for patients with alopecia, the need for training for GPs on alopecia, as well as a simplified and joined up pathway between primary and secondary healthcare.

Abstract Background Equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona remains an antemortem diagnostic challenge in some horses. Recent work suggested the use of real‐time PCR (rtPCR) on cerebrospinal fluid (CSF) as a promising diagnostic tool. Objective To evaluate the sensitivity and specificity of S. neurona rtPCR on CSF for EPM diagnosis using horses with EPM and S. neurona‐seropositive horses with other neurologic conditions. Animals Ninety‐nine horses with neurologic disease that underwent complete neurologic examination, CSF collection, and, if euthanized, necropsy including the central nervous system (CNS). Methods Retrospective case‐control study using banked CSF samples. Samples from horses with neurologic abnormalities and necropsy‐confirmed EPM diagnosis, presumptive EPM diagnosis using strict criteria (SnSAG2/4/3 ELISA serum:CSF titer ratios

There has been limited focus placed on exploring food insecurity within the UK-ex-Armed Forces population. The present study aims to build on initial work by investigating the prevalence and associated factors of food insecurity within UK veterans and their families and their current health status. 881 veterans (or a family member) who previously served in the Royal Navy and Royal Marines, Army and the Royal Air Force completed an online survey to explore health status, food insecurity and receipt of benefits. In total, 16.9% of survey respondents were part of food-insecure households, with 12% of these also experiencing some element of hunger. Working age, non-officer rank at the time of service discharge, not being married, living in rented accommodation, having at least one medical condition and in receipt of other benefits were significant risk factors associated with food insecurity. Understanding the specific risk factors associated with food insecurity is vital to develop personalised interventions and policies, such as income support programmes and affordable housing initiatives. However, more work is needed to further explore the factors associated with food insecurity, particularly in the long term.

IntroductionCOVID-19 restrictions created barriers to “business as usual” in healthcare but also opened the door to innovation driven by necessity. This manuscript (1) describes how ADVANCE, an in-person group perpetrator program to reduce intimate partner violence (IPV) against female (ex)partners by men in substance use treatment, was adapted for digitally-supported delivery (ADVANCE-D), and (2) explores the feasibility and acceptability of delivering ADVANCE-D to men receiving substance use treatment.MethodsFirstly, the person-based approach and mHealth development framework were used to iteratively adapt ADVANCE for digitally-supported delivery including conceptualization, formative research, and pre-testing. Then, a non-randomized feasibility study was conducted to assess male participants’ eligibility, recruitment, and attendance rates and uptake of support offered to their (ex)partners. Exploratory analyses on reductions in IPV perpetration (assessed using the Abusive Behavior Inventory; ABI) and victimization (using the revised ABI; ABI-R) at the end of the program were performed. Longitudinal qualitative interviews with participants, their (ex)partners, and staff provided an understanding of the program’s implementation, acceptability, and outcomes.ResultsThe adapted ADVANCE-D program includes one goal-setting session, seven online groups, 12 self-directed website sessions, and 12 coaching calls. ADVANCE-D includes enhanced risk management and support for (ex)partners. Forty-five participants who had perpetrated IPV in the past 12 months were recruited, forty of whom were offered ADVANCE-D, attending 11.4 (SD 9.1) sessions on average. Twenty-one (ex)partners were recruited, 13 of whom accepted specialist support. Reductions in some IPV perpetration and victimization outcome measures were reported by the 25 participants and 11 (ex)partners interviewed pre and post-program, respectively. Twenty-two participants, 11 (ex)partners, 12 facilitators, and 7 integrated support service workers were interviewed at least once about their experiences of participation. Overall, the program content was well-received. Some participants and facilitators believed digital sessions offered increased accessibility.ConclusionThe digitally-supported delivery of ADVANCE-D was feasible and acceptable. Remote delivery has applicability post-pandemic, providing greater flexibility and access. Given the small sample size and study design, we do not know if reductions in IPV were due to ADVANCE-D, time, participant factors, or chance. More research is needed before conclusions can be made about the efficacy of ADVANCE-D.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with liver and cardiovascular morbidity and mortality. Recently published NAFLD Quality Standards include 11 key performance indicators (KPIs) of good clinical care. This national study, endorsed by British Association for the Study of the Liver (BASL) and British Society of Gastroenterology (BSG), aimed to benchmark NAFLD care in UK hospitals against these KPIs. Methods: This study included all new patients with NAFLD reviewed in the outpatient clinic in the months of March 2019 and March 2022. Participating UK hospitals self-registered for the study through BASL/BSG. KPI outcomes were compared using Fisher’s exact or Chi-square tests. Results: Data from 776 patients with NAFLD attending 34 hospitals (England [25], Scotland [four], Wales [three], Northern Ireland [two]) were collected. A total of 85.3% of hospitals reported established local liver disease assessment pathways, yet only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment documented at the point of referral to secondary care. In secondary care, 79.1% of patients had fibrosis assessment. Assessment of cardiometabolic risk factors including obesity, type 2 diabetes, hypertension, and smoking were conducted in 73.2%, 33.0%, 19.3%, and 54.9% of all patients, respectively. There was limited documentation of diet (35.7%) and exercise advice (55.1%). Excluding those on statins, only 9.1% of patients with NAFLD at increased cardiovascular risk (T2DM and/or QRISK-3 >10%) had documented discussion of statin treatment. Significant KPI improvements from 2019 to 2022 were evident in use of non-invasive fibrosis assessment before secondary care referral, statin recommendations, and diet and exercise recommendations. Conclusions: This national study identified substantial variation in NAFLD management in the UK with clear areas for improvement, particularly fibrosis risk assessment before secondary care referral and management of associated cardiometabolic risk factors. Impact and implications: This study identified significant variation in the management of NAFLD in the UK. Only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment performed to identify those at greater risk of advanced liver disease before specialist referral. Greater emphasis is needed on the management of associated cardiometabolic risk factors in individuals with NAFLD. Hospitals with multidisciplinary NAFLD service provision had higher rates of fibrosis evaluation and assessment and management of cardiometabolic risk than hospitals without multidisciplinary services. Further work is needed to align guideline recommendations and real-world practice in NAFLD care.

Pregnancy can exacerbate or prompt the onset of stress-related disorders, such as post-traumatic stress disorder (PTSD). PTSD is associated with heightened stress responsivity and emotional dysregulation, as well as increased risk of chronic disorders and mortality. Further, maternal PTSD is associated with gestational epigenetic age acceleration in newborns, implicating the prenatal period as a developmental time period for the transmission of effects across generations. Here, we evaluated the associations between PTSD symptoms, maternal epigenetic age acceleration, and infant gestational epigenetic age acceleration in 89 maternal-neonatal dyads. Trauma-related experiences and PTSD symptoms in mothers were assessed during the third trimester of pregnancy. The MethylationEPIC array was used to generate DNA methylation data from maternal and neonatal saliva samples collected within 24 h of infant birth. Maternal epigenetic age acceleration was calculated using Horvath’s multi-tissue clock, PhenoAge and GrimAge. Gestational epigenetic age was estimated using the Haftorn clock. Maternal cumulative past-year stress (GrimAge: p = 3.23e-04, PhenoAge: p = 9.92e-03), PTSD symptoms (GrimAge: p = 0.019), and difficulties in emotion regulation (GrimAge: p = 0.028) were associated with accelerated epigenetic age in mothers. Maternal PTSD symptoms were associated with lower gestational epigenetic age acceleration in neonates (p = 0.032). Overall, our results suggest that maternal cumulative past-year stress exposure and trauma-related symptoms may increase the risk for age-related problems in mothers and developmental problems in their newborns.

Abstract Ultrasound‐guided cervical centesis has gained popularity as a method for collecting cerebrospinal fluid (CSF) from standing horses. There are anecdotal reports of neck stiffness, regional swelling, sensitivity to palpation, and fever after the procedure. We report 2 horses with complications that occurred within days of C1‐C2 centesis and ultimately resulted in euthanasia. Both C1‐C2 centesis were performed routinely, with CSF cytologic analysis providing no evidence of blood contamination. Post‐mortem examination revealed equine degenerative myeloencephalopathy as the primary disorder causing Horse 1's initial neurologic deficits, whereas Horse 2 did not have a distinct lesion explaining the horse's deficits. Both horses had evidence of subarachnoid hemorrhage at or near the centesis site with Wallerian axonal degeneration in the cranial cervical spinal cord. Although hemorrhage with associated axonal degeneration at the cervical centesis site appears to be rare, this complication of C1‐C2 centesis should be considered as this technique gains popularity.

Four wheat-based diets with either a low soluble content of non-starch polysaccharides (NSPs, 13 g/kg); low viscosity, LV) or a high content of NSPs (33.5 g/kg; high viscosity, HV), with and without exogenous xylanase (XYL), were fed to male Ross 308 broiler chickens from 7 to 21 days age. The enzyme was supplemented at 100 FXU/kg diet, and its preparation was based on endo-1,4-beta-xylanase produced by Aspergillus oryzae. Each diet was fed to eight pens, with five birds in each pen, following randomisation. Chicks fed XYL had an improved feed efficiency, hepatic coenzyme Q10, caecal butyric acid concentration, nitrogen digestibility (p < 0.05) and increased dietary ME (p < 0.001). Compared to HV, birds fed LV diets had reduced weight of proventriculus, gizzard and the pancreas and higher blood glutathione peroxidase and dietary ME (p < 0.05), but no differences were observed on nutrient digestibility and growth performance variables. This also suggests that birds may tolerate a greater dietary NSPs content; thus, further benefits may be obtained by the application of XYL in low energy wheat-based diets.

Building on previous research, this study explored differences in university professors’ perceptions about writing from the beginning to the end of the baccalaureate experience across five common disciplines including biology, business, computer science, engineering, and psychology. Survey data provide insights regarding the relative importance of various aspects of writing along with information about the volume of writing, the extent to which feedback was provided and resubmissions were allowed, the types of writing completed for exams, the greatest writing challenges, and the most salient writing purposes across disciplines and over time. While factors such as the writing challenges students faced, seemed unaffected by discipline or time in a particular discipline, other factors were noticeably influenced by the students’ specific discipline, whether students were at the beginning or end of their baccalaureate experience, or both. These factors included distinct differences in the purposes of writing as well as different perceptions of the importance of various aspects of writing across disciplines. An understanding of both these commonalities as well as the differences should be useful for practitioners and university administrators as well as the students themselves.

Abstract Background Compared to men in the general population, men in substance use treatment are more likely to perpetrate intimate partner abuse (IPA). The ADVANCE group intervention for men in substance use treatment is tailored to address substance use and IPA in an integrated way. In a feasibility trial pre-COVID, men who received the ADVANCE intervention via face-to-face group delivery showed reductions in IPA perpetration. Due to COVID-19, ADVANCE was adapted for remote digital delivery. Methods/design This mixed-methods non-randomised feasibility study, with a nested process evaluation, will explore the feasibility and acceptability of delivering the ADVANCE digital intervention to men in substance use treatment who have perpetrated IPA towards a female partner in the past year. Sixty men will be recruited from seven substance use treatment services in Great Britain. The ADVANCE digital intervention comprises a preparatory one-to-one session with a facilitator to set goals, develop a personal safety plan, and increase motivation and a preparatory online group to prepare men for taking part in the intervention. The core intervention comprises six fortnightly online group sessions and 12 weekly self-directed website sessions to recap and practise skills learned in the online group sessions. Each website session is followed by a one-to-one video/phone coaching session with a facilitator. Men will also receive their usual substance use treatment. Men’s female (ex) partners will be invited to provide outcome data and offered support from integrated safety services (ISS). Outcome measures for men and women will be sought post intervention (approximately 4 months post male baseline interview). Feasibility parameters to be estimated include eligibility, suitability, consent, recruitment, attendance, retention and follow-up rates. In-depth interviews or focus groups will explore the intervention’s acceptability to participants, facilitators and ISS workers. A secondary focus of the study will estimate pre-post-differences in outcome measures covering substance use, IPA, mental health, self-management, health and social care service use, criminal justice contacts and quality of life. Discussion Findings will inform the design of a multicentre randomised controlled trial evaluating the efficacy and cost-effectiveness of the ADVANCE digital intervention for reducing IPA. Trial registration The feasibility study was prospectively registered: ISRCTN66619273 .

Abstract Background Optimal management of cirrhosis is complex, and patients often lack knowledge and skills, which can affect self-management. We assessed patient knowledge about cirrhosis and examined whether knowledge was associated with clinical outcomes, healthcare service use, and healthcare costs. A cross-sectional ‘knowledge survey’ was conducted during 2018–2020. We assessed patient knowledge about cirrhosis and explore whether knowledge was associated with clinical outcomes, healthcare service use, and costs. Methods Patients with cirrhosis (n = 123) completed a ‘knowledge survey’. We calculated the proportion of correct answers to eight questions deemed to be “key knowledge” about cirrhosis by an expert panel, and dichotomized patients as ‘good knowledge’/‘poor knowledge’. Clinical data, healthcare costs, and health-related quality of life (SF-36) were available. Results 58.5% of patients had ‘good knowledge’ about cirrhosis. Higher education level was associated with higher odds of having ‘good knowledge’ about cirrhosis (adjusted-OR = 5.55, 95%CI 2.40–12.84). Compared to patients with ‘poor knowledge’, those with ‘good knowledge’ had a higher health status in the SF-36 physical functioning domain (p = 0.011), fewer cirrhosis-related admissions (adjusted incidence rate ratio [IRR] = 0.59, 95%CI 0.35–0.99) and emergency presentations (adj-IRR = 0.34, 95%CI 0.16–0.72), and more planned 1-day cirrhosis admissions (adj-IRR = 3.96, 95%CI 1.46–10.74). The total cost of cirrhosis admissions was lower for patients with ‘good knowledge’ (adj-IRR = 0.30, 95%CI 0.29–0.30). Conclusion Poor disease knowledge is associated with increased use and total cost of healthcare services. Targeted educational interventions to improve patient knowledge may be an effective strategy to promote a more cost-effective use of healthcare services.

IntroductionDigital exclusion, through lack of access and poor digital skills, can have an adverse impact on daily living. Not only did the COVID-19 pandemic dramatically impact the necessity of technology in our daily lives, but also reduced the availability of digital skills programmes. This study aimed to explore perceived facilitators and barriers of a digital skills programme that was delivered remotely (online) and to reflect on this form of training as a possible alternative to traditional face-to-face models.MethodsIndividual interviews were carried out with programme participants and the programme instructor.ResultsTwo themes were generated from this data: (a) Creating a unique learning environment; and (b) Encouraging further learning.DiscussionBarriers to digital delivery were evident, however, the individual and personalized delivery empowered participants within their own learning, supporting individuals to learn skills relevant to them and to continue their digital learning journey.

Cusatuzumab is a high-affinity, anti-CD70 monoclonal antibody under investigation in acute myeloid leukemia (AML). This two-part, open-label, multicenter, phase I/II trial evaluated cusatuzumab plus azacitidine in patients with newly diagnosed AML ineligible for intensive chemotherapy. Patients received a single dose of cusatuzumab at one of four dose levels (1, 3, 10, or 20 mg/kg) 14 days before starting combination therapy. In phase I dose escalation, cusatuzumab was then administered on days 3 and 17, in combination with azacitidine (75 mg/m2) on days 1-7, every 28 days. The primary objective in phase I was to determine the recommended phase II dose (RP2D) of cusatuzumab plus azacitidine. The primary objective in phase II was efficacy at the RP2D (selected as 10 mg/kg). Thirty-eight patients were enrolled: 12 in phase I (three per dose level; four with European LeukemiaNet 2017 adverse risk) and 26 in phase II (21 with adverse risk). An objective response (≥partial remission) was achieved by 19/38 patients (including 8/26 in phase II); 14/38 achieved complete remission. Eleven patients (37.9%) achieved an objective response among the 29 patients in phase I and phase II treated at the RP2D. At a median follow-up of 10.9 months, median duration of first response was 4.5 months and median overall survival was 11.5 months. The most common treatment-emergent adverse events were infections (84.2%) and hematologic toxicities (78.9%). Seven patients (18.4%) reported infusion-related reactions, including two with grade 3 events. Thus, cusatuzumab/azacitidine appears generally well tolerated and shows preliminary efficacy in this setting. Investigation of cusatuzumab combined with current standard-of-care therapy, comprising venetoclax and azacitidine, is ongoing.

Abstract The current mixed methods study sought to investigate the actual as well as the perceived practices and alignment with animal-assisted interventions (AAI) ethics and standards of mental health practitioners that partner with an animal in their practice. While the quantitative findings suggested awareness and integration of standards and ethical practice, the qualitative results painted a somewhat different picture. Qualitative findings suggest a great deal of inconsistency in the attitudes and actions of practitioners regarding their alignment with standards and ethical practice. These inconsistencies are explored and then followed by specific recommendations regarding training and education, supervision, informed consent practices, documentation, and humane treatment for animal partners.

BackgroundWhilst the uniqueness of loneliness and social isolation is now recognised for members of the Armed Forces Community, there is currently a lack of evidence examining these experiences within the Military Widow/er population. Therefore, this scoping review aimed to search and synthesise the current evidence base exploring experiences of loneliness and social isolation in this community.MethodSix databases were searched; ASSIA; CINAHL; ProQuest Dissertation & Theses Global; PsycArticles; Medline; Web of Science. Any article type was included if they focused on UK or international Military Widows and loneliness and social isolation. In the absence of loneliness and social isolation, related aspects were included, for example, social support.ResultsA thematic synthesis was completed on the nine eligible papers, where key findings were coded and generated into four themes; Experiences of Loneliness and Social Isolation, The Uniqueness of the Military, Access to Social Support, and The Importance of Peer Support.ConclusionsEvidence supports the need for military-specific support services with peers who recognise the individuals' unique experiences of loneliness and social isolation. None of the available evidence focused specifically on social isolation, however this was often prevalent in the results. All of the studies were carried out in the USA and Israel, with none including the views of widowers. Further evidence is required, particularly relating to a UK-context.

Abstract Background We aimed to establish what core elements were required in a group therapy programme for men who disclose perpetrating intimate partner abuse in a substance use setting and develop, and test the feasibility of delivering an intervention in this setting. Methods We describe the theoretical development and feasibility testing of an integrated substance use and intimate partner abuse intervention (‘ADVANCE’) for delivery in substance use services. We employed a comprehensive eight-stage process to guide this development applying the ‘COM-B’ (‘capability’, ‘opportunity’, ‘motivation’ and ‘behaviour’) model for intervention design which specifies the following: (1) define the problem, (2) select the target behaviour, (3) specify the target behaviour, (4) identify what needs to change, (5) identify intervention functions, (6) identify policy categories, (7) select behaviour change techniques, and (8) design a mode of delivery. The development was informed by primary research conducted by the authors, consulting with organisation steering groups and by those with personal experiences. The identified targets for intervention and mode and method of delivery were then refined over 4 intervention development meetings, using the nominal group technique with the ADVANCE experts, then further refined following consultation with service user groups and wider expert groups via a learning alliance meetings. Results Our final intervention, the ADVANCE intervention consisted of a group intervention comprising of up to four pre-group individual interviews, followed by 12 × 2-h group sessions supported by integrated safety work for victim/survivors, and risk and safety support and integrity support for the professionals. The main targets for change were personal goal planning, self-regulation, and attitudes and beliefs supporting intimate partner abuse. The intervention was regarded as very acceptable to both staff and clients in substance use services, with group attendees reported positive behaviour changes and development of new skills. Conclusion We have demonstrated the ability to employ a structured eight-step process to develop an integrated intervention to address substance use-related intimate partner abuse that is acceptable to staff and clients in substance use services. This led to a feasibility study (ISRCTN 79435190) involving 104 men and 30 staff at three different locations across the UK was conducted to assess the feasibility and acceptability of the intervention and to refine the content and approach to delivery (BMC Public Health, 21: 980, 2021).

Abstract Background Substance use is a risk factor for intimate partner abuse (IPA) perpetration. Delivering perpetrator interventions concurrently with substance use treatment shows promise. Methods The feasibility of conducting an efficacy and cost-effectiveness trial of the ADVANCE 16-week intervention to reduce IPA by men in substance use treatment was explored. A multicentre, parallel group individually randomised controlled feasibility trial and formative evaluation was conducted. Over three temporal cycles, 104 men who had perpetrated IPA towards a female (ex) partner in the past year were randomly allocated to receive the ADVANCE intervention + substance use treatment as usual (TAU) (n = 54) or TAU only (n = 50) and assessed 16-weeks post-randomisation. Participants’ (ex) partners were offered support and 27 provided outcome data. Thirty-one staff and 12 men who attended the intervention participated in focus groups or interviews that were analysed using the framework approach. Pre-specified criteria assessed the feasibility of progression to a definitive trial: 1) ≥ 60% of eligible male participants recruited; 2) intervention acceptable to staff and male participants; 3) ≥ 70% of participants followed-up and 4) levels of substance use and 5) IPA perpetrated by men in the intervention arm did not increase from average baseline level at 16-weeks post-randomisation. Results 70.7% (104/147) of eligible men were recruited. The formative evaluation confirmed the intervention’s acceptability. Therapeutic alliance and session satisfaction were rated highly. The overall median rate of intervention session attendance (of 14 compulsory sessions) was 28.6% (range 14.3–64.3% by the third cycle). 49.0% (51/104) of men and 63.0% (17/27) of their (ex) partners were followed-up 16-weeks post-randomisation. This increased to 100% of men and women by cycle three. At follow-up, neither substance use nor IPA perpetration had worsened for men in the intervention arm. Conclusions It was feasible to deliver the ADVANCE intervention in substance use treatment services, although it proved difficult to collect data from female (ex)partners. While some progression criteria were met, others were not, although improvements were demonstrated by the third cycle. Lessons learned will be implemented into the study design for a definitive trial of the ADVANCE intervention. Trial registration ISRCTN79435190 prospectively registered 22nd May 2018.

Abstract. Spontaneous bacterial peritonitis (SBP), a common infection in patients with cirrhosis and ascites, is associated with high morbidity and mortality. The aim of this study was to investigate changes in the epidemiology of ascites fluid infections over time in an Australian population, including patient demographics, trends in mortality, length of hospital stay and the nature and antibiotic resistance profile of causative organisms. An observational descriptive population-based epidemiological study of patients with cirrhosis admitted to public hospitals in Queensland during 2008–2017 was performed, linking demographic/clinical and microbiology data. Among 103,165 hospital admissions of patients with cirrhosis, ascites was present in 16,550 and in 60% (9977) a sample of ascitic fluid was tested. SBP was diagnosed in 770 admissions (neutrophil count >250/ml) and bacterascites in 552 (neutrophil count

Evidence suggests that mental health interventions are more effective when they consider the whole context of schools; addressing the needs of all students, their families, and staff; otherwise known as a whole-school approach (WSA). The UK Government is piloting WSAs to transform mental health and wellbeing by locating educational mental health practitioners in educational settings across England. This study aims to develop a ‘bottom-up’ understanding of the contextual factors and mechanisms that underlie WSAs in Trailblazer schools in the North East and North Cumbria, to gain insight into the facilitators and barriers of delivering a WSA, and optimal evaluation methods. To undertake a realist evaluation, we included the generation of initial programme theories from existing academic literature and policy documents; ‘theory gleaning’ interviews with NHS/local authority stakeholders, Trailblazer staff and school senior leaders; refining and development of theories; and individual interviews and focus groups with pupils, parent/carers and school staff. The findings will enable Trailblazer partners to better understand how their WSAs to mental health contain the essential components for transformation in schools in the region. This will contribute to the embedding of continuous evaluation into regional Trailblazers’ practice for participating schools, for subsequent annual waves and producing relevant findings for non-Trailblazer schools. Complementing the national evaluation of all 25 Wave 1 Trailblazer pilot sites, this study will generate an explanatory theoretical account of how to optimally design, implement and evaluate WSAs by exploring the contextual factors associated with implementation of WSAs.

Abstract Background Strong evidence exists that substance use is a contributory risk factor for intimate partner abuse (IPA) perpetration. Men in substance use treatment are more likely to perpetrate IPA than men from the general population. Despite this, referral pathways are lacking for this group. This trial will assess the feasibility of conducting an evaluation trial of a tailored integrated intervention to address substance use and IPA perpetration to men in substance use treatment. Methods/design ADVANCE is a multicentre, parallel-group individually randomised controlled feasibility trial, with a nested formative evaluation, comparing an integrated intervention to reduce IPA + substance use treatment as usual (TAU) to TAU only. One hundred and eight men who have perpetrated IPA in the past 12 months from community substance use treatment in London, the West Midlands, and the South West will be recruited. ADVANCE is a manualised intervention comprising 2–4 individual sessions (2 compulsory) with a keyworker to set goals, develop a personal safety plan and increase motivation and readiness, followed by a 12-session weekly group intervention delivered in substance use services. Men will be randomly allocated (ratio 1:1) to receive the ADVANCE intervention + TAU or TAU only. Men’s female (ex) partners will be invited to provide outcome data and offered support from integrated safety services (ISS). Regular case management meetings between substance use and ISS will manage risk. Outcome measures will be obtained at the end of the intervention (approximately 4 months post-randomisation) for all male and female participants. The main objective of this feasibility trial is to estimate parameters required for planning a definitive trial including rates of consent, recruitment, and follow-up by site and group allocation. Nested formative evaluation including focus groups and in-depth interviews will explore the intervention’s acceptability to participants, group facilitators, keyworkers and ISS workers. Secondary outcomes include substance use, IPA, mental health, self-management, health and social care service use, criminal justice contacts, and quality of life. Discussion Findings from this feasibility trial will inform the design of a multicentre randomised controlled trial evaluating the efficacy and cost-effectiveness of the ADVANCE intervention for reducing IPA and improving the well-being of female (ex)partners. Trial registration ISRCTN79435190 .

Previous studies have identified localized associations between childhood environment – namely their socio-economic status (SES) – and particular neural structures. The primary aim of the current study was to test whether associations between SES and brain structure are widespread or limited to specific neural pathways. We employed advances in whole-brain structural connectomics to address this. Diffusion tensor imaging was used to construct whole-brain connectomes in 113 6−12 year olds. We then applied an adapted multi-block partial-least squares (PLS) regression to explore how connectome organisation is associated with childhood SES (parental income, education levels, and neighbourhood deprivation). The Fractional Anisotropy (FA) connectome was significantly associated with childhood SES and this effect was widespread. We then pursued a secondary aim, and demonstrated that the connectome mediated the relationship between SES and cognitive ability (matrix reasoning and vocabulary). However, the connectome did not significantly mediate SES relationships with academic ability (maths and reading) or internalising and externalising behavior. This multivariate approach is important for advancing our theoretical understanding of how brain development may be shaped by childhood environment, and the role that it plays in predicting key outcomes. We also discuss the limitations with this new methodological approach.

Children and adolescents with developmental problems are at increased risk of experiencing mental health problems. The Strengths and Difficulties Questionnaire (SDQ) is widely used as a screener for detecting mental health difficulties in these populations, but its use thus far has been restricted to groups of children with diagnosed disorders (e.g., ADHD). Transdiagnostic approaches, which focus on symptoms and soften or remove the boundaries between traditional categorical disorders, are increasingly adopted in research and practice. The aim of this study was to assess the potential of the SDQ to detect concurrent mental health problems in a transdiagnostic sample of children. The sample were referred by health and educational professionals for difficulties related to learning (N = 389). Some had one diagnosis, others had multiple, but many had no diagnoses. Parent-rated SDQ scores were significantly positively correlated with parent ratings of mental health difficulties on the Revised Child Anxiety and Depression Scale (RCADS). Ratings on the SDQ Emotion subscale significantly predicted the likelihood of having concurrent clinical anxiety and depression scores. Ratings on the Hyperactivity subscale predicted concurrent anxiety levels. These findings suggest the SDQ could be a valuable screening tool for identifying existing mental health difficulties in children recognized as struggling, as it can be in typically developing children and those with specific diagnoses.

This text traces the development of an aspiring biracial teacher’s growing understandings of African American youth he tutors. It deploys a Bakhtinian conceptual framework for how we might develop new understandings of ourselves through relationships and dialogues with others. It offers examples from one aspiring teacher’s experiences to illustrate how when individuals look inward, that they can come to different interpretations of who people are and why they behave as they do. Further, it

Abstract Background Worldwide, over 14% of individuals hospitalized for psychiatric reasons have readmissions to hospitals within 30 days after discharge. Predicting patients at risk and leveraging accelerated interventions can reduce the rates of early readmission, a negative clinical outcome (i.e., a treatment failure) that affects the quality of life of patient. To implement individualized interventions, it is necessary to predict those individuals at highest risk for 30-day readmission. In this study, our aim was to conduct a data-driven investigation to find the pharmacological factors influencing 30-day all-cause, intra- and interdepartmental readmissions after an index psychiatric admission, using the compendium of prescription data (prescriptome) from electronic medical records (EMR). Methods The data scientists in the project received a deidentified database from the Mount Sinai Data Warehouse, which was used to perform all analyses. Data was stored in a secured MySQL database, normalized and indexed using a unique hexadecimal identifier associated with the data for psychiatric illness visits. We used Bayesian logistic regression models to evaluate the association of prescription data with 30-day readmission risk. We constructed individual models and compiled results after adjusting for covariates, including drug exposure, age, and gender. We also performed digital comorbidity survey using EMR data combined with the estimation of shared genetic architecture using genomic annotations to disease phenotypes. Results Using an automated, data-driven approach, we identified prescription medications, side effects (primary side effects), and drug-drug interaction-induced side effects (secondary side effects) associated with readmission risk in a cohort of 1275 patients using prescriptome analytics. In our study, we identified 28 drugs associated with risk for readmission among psychiatric patients. Based on prescription data, Pravastatin had the highest risk of readmission (OR = 13.10; 95% CI (2.82, 60.8)). We also identified enrichment of primary side effects (n = 4006) and secondary side effects (n = 36) induced by prescription drugs in the subset of readmitted patients (n = 89) compared to the non-readmitted subgroup (n = 1186). Digital comorbidity analyses and shared genetic analyses further reveals that cardiovascular disease and psychiatric conditions are comorbid and share functional gene modules (cardiomyopathy and anxiety disorder: shared genes (n = 37; P = 1.06815E-06)). Conclusions Large scale prescriptome data is now available from EMRs and accessible for analytics that could improve healthcare outcomes. Such analyses could also drive hypothesis and data-driven research. In this study, we explored the utility of prescriptome data to identify factors driving readmission in a psychiatric cohort. Converging digital health data from EMRs and systems biology investigations reveal a subset of patient populations that have significant comorbidities with cardiovascular diseases are more likely to be readmitted. Further, the genetic architecture of psychiatric illness also suggests overlap with cardiovascular diseases. In summary, assessment of medications, side effects, and drug-drug interactions in a clinical setting as well as genomic information using a data mining approach could help to find factors that could help to lower readmission rates in patients with mental illness.

AAI is a transdisciplinary field that has grown exponentially in recent decades. This growth has not always been synergistic across fields, creating a need for more consistent language and standards, a call for which many professionals in the field have made. Under the umbrella of human–animal interactions (HAI) is animal-assisted interventions (AAIs), which have a more goal-directed intention with animals who have been assessed for therapeutic, educational, or vocational work. The current article offers a brief history and efficacy of HAI, describes the limitations and gaps within the field and recommends a new set of competencies and guidelines that seek to create some of the needed common language and standards for AAI work to address these limitations.

There is limited research assessing the effectiveness of Animal-Assisted Therapy in at-risk adolescent populations. In a recent study, 138 adjudicated adolescents participated in a randomized controlled trial of an animal-assisted intervention, in which participants either trained shelter dogs (Teacher's Pet group) or walked the dogs (control group), with both groups participating in classroom work related to dogs (1). Journal writing was a part of class activities for all youth in the study. Conventional assessments of youth behavior made by staff or youth themselves did not demonstrate the expected differences between the groups favoring the dog training group, as youth in both groups showed a significant increase in staff and youth rated internalizing behavior problems and empathy from the beginning to the end of the project (1). However, subsequent analysis of the journal content from 73 of the adjudicated youth reported here, did reveal significant differences between treatment and control groups, favoring the Teacher's Pet group. Youth participating in the dog training intervention showed through their journal writing greater social-cognitive growth, more attachment, and more positive attitudes toward the animal-assisted intervention compared to youth in the control group. The 73 youth whose journals were available were very similar to youth in the larger group. Their results illustrate that journaling can be a useful method of assessing effects of similar animal-assisted interventions for at-risk youth. Writing done by youth receiving therapy appeared to promote self-reflection, desirable cognitive change, and prosocial attitudes that may signify improving quality of life for such youth. The expressive writing of participants could reveal important effects of treatment beyond the behavioral changes that are often the targeted outcomes of animal-assisted interventions.

Through the years, the range of services involving animals benefiting people, often described as “animal-assisted interventions” (AAIs), has been plagued with confusing and inconsistent taxonomy, terminology, and definitions. This has caused difficulties for the delineation of roles of service providers, for the recipients of services, as well as for the preparation, training, and expectations of the animals that work in different roles. It can be argued that these difficulties have compromised the development of the field in terms of establishing agreed standards of practice, qualifications, and competencies and adopting good animal welfare practices. It has also likely limited the base of evidence, as search terms used to access studies are not consistent, and study protocols are difficult to compare, lacking uniformity in terminology. Additionally, the current terminology cannot accommodate the expansion and diversification of programs in recent years, which is likely to continue as the field evolves. Establishing internationally agreed upon uniform taxonomy, terminology, and definitions is crucial to more accurately reflect the key features of different approaches, to define the scope and competencies for different service providers and their animals, to provide transparency about services for recipients, and to ensure the appropriate preparation, training, and support of the animals that work with them., The recommendations in this article are the result of an international work group that convened over the course of two years. The umbrella term animal-assisted services (AAS) is proposed, defined as services that are facilitated, guided or mediated by a health or human service provider or educator, who works with and maintains the welfare of a specially alongside a specially qualifying animal to provide therapeutic, educational, supportive and/or ameliorative processes aimed at enhancing the well-being of humans. AAS are further categorized into three main areas: treatment, education, and support programs. A recommendation for provider-specific terminology is also suggested. The aim of these proposals is to set clear expectations and boundaries for each specialty of practice, without compromising the richness and diversity of each approach. The adoption of this new umbrella term and its categories is intended to improve clarity for all involved in the receipt and delivery of services, as well as for those who study their effects.

Health care and human service providers may include dogs in formal intervention settings to positively impact human physical, cognitive and psychosocial domains. Dogs working within this context are asked to cope with a multitude of variables including settings, populations, activities, and schedules. In this article, the authors highlight how both the preparation and operation of dogs within animal-assisted therapy (AAT) differs from less structured animal-assisted activities (AAA) and more exclusive assistance animal work; the authors highlight the gaps in our knowledge in this regard, and propose an ethically sound framework for pragmatic solutions. This framework also emphasizes the need for good dog welfare to safeguard all participants. If dogs are not properly matched to a job or handler, they may be subjected to unnecessary stress, anxiety, and miscommunication that can lead to disinterest in the work, overt problematic behavioral or health outcomes, or general unsuitability. Such issues can have catastrophic outcomes for the AAT. The authors propose standards for best practices for selection, humane-based preparation and training, and ongoing evaluation to ensure the health, welfare and well-being of dogs working in AAT, which will have concomitant benefits for clients and the professionalism of the field.

Recent years have seen increasing integration of language corpora into second language instruction. Arabic’s rich polysemy and multiglossic spectrum can complicate vocabulary development for learners. Corpora thus offer great potential as complementary tools for Arabic learners. This study examines two variants of a corpusbased exercise used with fourth-semester adult Arabic learners. Learners analyzed data for select Arabic vocabulary items in the online arabiCorpus. Students in both variant groups proved themselves adept at using the corpus, interpreting data, and articulating metalinguistic hypotheses about nuances of meaning.

Background A pharmacokinetically derived schedule of flavopiridol administered as a 30 min intravenous bolus followed by 4-hour continuous intravenous infusion (IVB/CIVI) is active in fludarabine-refractory chronic lymphocytic leukemia, but no studies examining the feasibility and maximum tolerated dose of this schedule have been reported in acute leukemia.Design and Methods We conducted a phase I dose escalation trial of single-agent flavopiridol in adults with relapsed/refractory acute leukemias, utilizing a modification of the intravenous bolus/continuous intravenous infusion approach, intensifying treatment for administration on days 1, 2, and 3 of 21-day cycles.Results Twenty-four adults with relapsed/refractory acute myeloid leukemia (n=19) or acute lymphoblastic leukemia (n=5) were enrolled. The median age was 62 years (range, 23–78). The maximum tolerated dose of flavopiridol was 40mg/m2 intravenous bolus plus 60mg/m2 continuous intravenous infusion (40/60). The dose limiting toxicity was secretory diarrhea. Life-threatening hyperacute tumor lysis syndrome requiring hemodialysis on day 1 was observed in one patient. Pharmacokinetics were dose-dependent with increased clearance observed at the two highest dose levels. Diarrhea occurrence and severity significantly correlated with flavopiridol concentrations at the end of the 4-hour infusion, volume of distribution, and elimination half-life. Modest anti-leukemic activity was observed, with most patients experiencing dramatic but transient reduction/clearance of circulating blasts lasting for 10–14 days. One refractory acute myeloid leukemia patient had short-lived complete remission with incomplete count recovery.Conclusions Flavopiridol as a single agent given by intravenous bolus/continuous intravenous infusion causes marked, immediate cytoreduction in relapsed/refractory acute leukemias, but objective clinical responses were uncommon. With this schedule, the dose is limited by secretory diarrhea (ClinicalTrials.gov Identifier: NCT00101231).

Research Findings: Strong relationships among children, families, and early care and education (ECE) providers are key to quality infant-toddler care. These relationships are shaped during the initial transition period to group care. We used a mixed methods approach to (a) assess maternal perspectives on the transition to group care, (b) explore mothers' perceptions of factors that made for easy or difficult transitions, and (c) examine associations between maternal and child characteristics and the ease of the transition. Through qualitative interviews, mothers identified factors that played a role in their child's transition, including the child's age, the ECE provider's support, and the number of transitions the child experienced. For mothers, an easy transition was characterized by ease of child adjustment to group care, comfort with nonparental care and returning to work, and being able to exercise some control over the transition. Quantitative analyses revealed that an easy child transition was associated with younger child age, low maternal distress reactions to child distress, and low child social fearfulness. Higher maternal depressive symptoms and maternal distress reactions to child distress were associated with mothers having a difficult transition. Practice or Policy: Implications of the findings for ECE provider training and ECE policy development related to transitions are discussed.

Deploying Russian philosopher M. M. Bakhtin's notions of utterances or communicative interactions, we explore the life histories of two administrators at State University, a predominantly White institution of higher education in the Midwestern United States. In particular, we explore how working with White students, peers, and supervisors demands that staff members of color find means of answering overt and implied criticisms of their daily work. We name and analyze metaphors each participant uses to define ways she negotiates a campus culture that privileges some and interprets others as oppositional when they call into question long held institutional priorities and practices.