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Background: We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England. Methods: 108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models. Results: Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71–0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74–0.87, p < 0.0001). Referral to substance use services and 'other' services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78–0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79–0.94, p = 0.001). Conclusions: SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care. [ABSTRACT FROM AUTHOR]

We have carried out melanoma case-control comparisons for six vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) and serum 25-hydroxyvitamin D(3) levels in order to investigate the role of vitamin D in melanoma susceptibility. There was no significant evidence of an association between any VDR SNP and risk in 1028 population-ascertained cases and 402 controls from Leeds, UK. In a second Leeds case-control study (299 cases and 560 controls) the FokI T allele was associated with increased melanoma risk (odds ratio (OR) 1.42, 95% confidence interval (CI) 1.06-1.91, p=0.02). In a meta-analysis in conjunction with published data from other smaller data sets (total 3769 cases and 3636 controls), the FokI T allele was associated with increased melanoma risk (OR 1.19, 95% CI 1.05-1.35), and the BsmI A allele was associated with a reduced risk (OR 0.81, 95% CI 0.72-0.92), in each instance under a parsimonious dominant model. In the first Leeds case-control comparison cases were more likely to have a higher body mass index (BMI) than controls (p=0.007 for linear trend). There was no evidence of a case-control difference in serum 25-hydroxyvitamin D(3) levels. In 1043 incident cases from the first Leeds case-control study, a single estimation of serum 25-hydroxyvitamin D(3) level taken at recruitment was inversely correlated with Breslow thickness (p=0.03 for linear trend). These data provide evidence to support the view that vitamin D and VDR may have a small but potentially important role in melanoma susceptibility, and putatively a greater role in disease progression. [ABSTRACT FROM AUTHOR]

Mesenteric fat, a type of intraperitoneal adipose tissue, plays a critical role in protection and the immune response. Loss of mesenteric fat is a known consequence of a variety of clinical conditions; however, visual documentation of this rare occurrence is not available in the literature searched. Here we report a case of significant loss of mesenteric fat identified during educational dissection of a 79-year-old male fresh frozen donor cadaver, causing the mesenteric folds to appear transparent. The gross anatomical characteristics, clinical importance, and educational significance of this abnormality are described in this report. Knowledge of this condition may be of interest to clinicians, and documentation could benefit anatomists and educators dissecting and teaching in the laboratory setting., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Tensor fasciae suralis (TFS) is an accessory muscle of the posterior lower extremity. Although TFS has been documented in cadaveric and radiological reports, its prevalence remains unknown. The TFS variant is noteworthy to anatomists, as it may be encountered in the dissection laboratory, and clinicians, as the muscle could potentially cause confusion during physical examination or diagnostic imaging. Multiple variations of TFS have been reported in the literature, suggesting the need for a classification system. We dissected 236 formalin-fixed cadaveric lower limbs to determine the prevalence of TFS. The PubMed and MEDLINE databases were searched to compare the anatomical features of independent TFS case reports. In our prevalence study, the TFS muscle was identified in three lower limbs (1.3%). In total, 38 cases of TFS (32 cadaveric and six radiological) were identified in the literature. Our literature review revealed that the accessory muscle most often arises as a single head from the long head of the biceps femoris, yet many other presentations have been documented. The need for a classification system to distinguish between the subtypes of TFS became apparent during the literature review. Tensor fasciae suralis is a rare muscle, present in only 3 of 236 (1.3%) cadaveric lower limbs dissected in this study. We propose the use of a classification system, based on muscle origin and number of heads, to better organize the subtypes of TFS., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

The etiology of sirenomelia is currently unknown. Data are limited in comparing external and internal abnormalities using modern imaging technologies and molecular genetic analysis. The purpose of the current study was designed to compare external and internal anatomical defects in two cases of sirenomelia and Potter's sequence. Considered rare, Potter's sequence is a fetal disorder with characteristic features of bilateral renal agenesis, obstructive uropathy, atypical facial appearance, and limb malformations. The internal and external malformations of two term fetuses with sirenomelia and Potter's sequence were compared using assessment of external features, radiography and MRI on internal structures, and molecular genetic studies on sex determination. Data reveal that both fetuses were male and manifested with an overlapping but distinct spectrum of abnormalities. Principal differences were noted in the development of the ears, brain, urogenital system, lower limbs, pelvis, and vertebral column. Defects of the axial mesoderm are likely to underlie the abnormalities seen in both fetuses. The first one, which had only caudal defects, was found to have a spectrum of abnormalities most similar to those associated with more severe forms of the small pelvic outlet syndrome, although the structure and orientation of the sacrum and iliae were different from previously reported cases. The other had both caudal and cranial defects, and was most similar to those described in the axial mesodermal dysplasia syndrome. Defects associated with sirenomelia can be evaluated with standard gross anatomy examination, radiology, MRI, and modified PCR techniques to determine anatomical abnormalities and the sex of preserved specimens, respectively. Evidence indicated that sirenomelia could be developed via various etiologies., (© 2024 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

The occurrence of variations in human arterial branching of the upper limb has been commonly reported in peer-reviewed literature. However, the variability of upper limb arterial patterns may be underappreciated in medical practice, which can result in clinical and surgical errors. Here we report a case of a rare, unilateral arterial variation of the left upper limb of a 76-year-old Caucasian male cadaver, discovered during a routine educational dissection. Observed characteristics of the variation include a high brachial artery bifurcation into a superficial brachioulnoradial artery and brachial artery continuing as the interosseous artery and then a bifurcation of the superficial brachioulnoradial artery into a superficial radial and a superficial ulnar artery, which eventually contribute to the formation of the superficial palmar arch. The anatomical characteristics, prevalence, embryological origin, and clinical significance of the variation are discussed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background : Nursing professionals are an occupational group at increased risk of suicide, but little is known about self-harm in this population. Aims : To investigate the characteristics of nurses and midwives who present to hospital following self-harm. Method: We used data from the Oxford Monitoring System for Self-Harm to identify nurses and midwives who presented to the general hospital in Oxford during 2010-2020 following an episode of self-harm and received a psychosocial assessment. Results: During the eleven-year study period, 107 presentations of self-harm involving 81 nurses and midwives were identified. Self-poisoning was the most common self-harm method (71.6%), with antidepressants and paracetamol most frequently involved. Many had consumed alcohol before (43.8%) or during (25.3%) the self-harm act. Some individuals had high or very high suicide intent scores (22/70, 31.4%). Common problems preceding self-harm included problems with a partner (46.9%), psychiatric disorder (29.6%), and problems with employment (27.2%), family (24.7%), and alcohol (23.5%). A range of aftercare options were offered following presentation. Limitations: This study was limited to data from a single hospital. Conclusion: Prevention and management of self-harm within this occupational group requires preventative strategies and availability of interventions addressing the range of factors that may contribute to self-harm, especially relationship problems, psychiatric disorders, employment problems, and alcohol misuse.

Introduction: Physical activity is important to prevent and manage multiple chronic medical conditions. The objective of this study was to describe the implementation of a physical activity vital sign (PAVS) in a primary care setting and examine the association between physical activity with demographic characteristics and chronic disease burden., Methods: We extracted data from the electronic medical records of patients who had visits from July 2018 through January 2020 in a primary care clinic in which PAVS was implemented as part of the intake process. Data collected included self-reported physical activity, age, sex, body mass index, race, ethnicity, and a modified Charlson Comorbidity Index score indicating chronic disease burden. We classified PAVS into 3 categories of time spent in moderate to strenuous intensity physical activity: consistently inactive (0 min/wk), inconsistently active (<150 min/wk), and consistently active (≥150 min/wk). We used χ 2 tests of independence to test for association between PAVS categories and all other variables., Results: During the study period, 13,704 visits, corresponding to 8,741 unique adult patients, had PAVS recorded. Overall, 18.1% of patients reported being consistently inactive, 48.3% inconsistently active, and 33.7% consistently active. All assessed demographic and clinical covariates were associated with PAVS classification (all P < .001). Larger percentages of consistent inactivity were reported for female, older, and underweight or obese patients. Larger percentages of consistent activity were reported for male, younger, and normal weight or overweight patients., Conclusion: Using PAVS as a screening tool in primary care enables physicians to understand the physical activity status of their patients and can be useful in identifying inactive patients who may benefit from physical activity counseling.

Background: Very little is known about self-harm in children. We describe the characteristics and outcomes of children under 13 years who presented following self-harm to five hospitals in England., Methods: We included children under 13 years who presented after self-harm to hospitals in the Multicentre Study of Self-harm in England. Information on patients' characteristics and method of self-harm was available through monitoring of self-harm in the hospitals. Area level of socioeconomic deprivation was based on the English Index of Multiple Deprivation (IMD)., Results: 387 children aged 5-12 years presented to the study hospitals in 2000-2016, 39% of whom were 5-11 years. Boys outnumbered girls 2:1 at 5-10 years. The numbers of boys and girls were similar at age 11, while at 12 years there were 3.8 girls to every boy. The proportion of study children living in neighbourhoods ranked most deprived (43.4%) was twice the national average. 61.5% of children self-poisoned, 50.6% of them by ingesting analgesics. Of children who self-injured, 45.0% self-cut/stabbed, while 28.9% used hanging/asphyxiation. 32% of the children had a repeat hospital presentation for self-harm, 13.5% re-presented within a year., Conclusions: Gender patterns of self-harm until age 11 years are different to those of adolescents, with a male preponderance, especially in 5-10 years, and hanging/suffocation being more common. The frequent use of self-poisoning in this age group highlights the need for public health messages to encourage safer household storage of medicines. Self-harm in children is strongly associated with socioeconomic deprivation; understanding the mechanisms involved could be important in effective prevention., (© 2021. The Author(s).)

Introduction: The COVID-19 pandemic and resulting public health measures may have major impacts on mental health, including on self-harm. We have investigated what factors related to the pandemic influenced hospital presentations following self-harm during lockdown in England., Method: Mental health clinicians assessing individuals aged 18 years and over presenting to hospitals in Oxford and Derby following self-harm during the period March 23rd to May 17, 2020 recorded whether the self-harm was related to the impact of COVID-19 and, if so, what specific factors were relevant. These factors were organized into a classification scheme. Information was also collected on patients' demographic characteristics, method of self-harm and suicide intent., Results: Of 228 patients assessed, in 46.9% (N = 107) COVID-19 and lockdown restrictions were identified as influencing self-harm. This applied more to females than males (53.5%, N = 68/127 v 38.6%, N = 39/101, χ 2  = 5.03, p = 0.025), but there were no differences in age, methods of self-harm or suicide intent between the two groups. The most frequent COVID-related factors were mental health issues, including new and worsening disorders, and cessation or reduction of services (including absence of face-to-face support), isolation and loneliness, reduced contact with key individuals, disruption to normal routine, and entrapment. Multiple, often inter-connected COVID-related factors were identified in many patients., Conclusions: COVID-related factors were identified as influences in nearly half of individuals presenting to hospitals following self-harm in the period following introduction of lockdown restrictions. Females were particularly affected. The fact that mental health problems, including issues with delivery of care, predominated has implications for organisation of services during such periods. The contribution of isolation, loneliness and sense of entrapment highlight the need for relatives, friends and neighbours to be encouraged to reach out to others, especially those living alone. The classification of COVID-related factors can be used as an aide-memoire for clinicians., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Self-harm and suicide in children and adolescents are growing problems, and self-harm is associated with a significant risk of subsequent death, particularly suicide. Long-term follow-up studies are necessary to examine the extent and nature of this association., Methods: For this prospective observational cohort study, we used data from the Multicentre Study of Self-harm in England for all individuals aged 10-18 years who presented to the emergency department of five study hospitals in Oxford, Manchester, and Derby after non-fatal self-harm between Jan 1, 2000, and Dec 31, 2013. Deaths were identified through the Office for National Statistics via linkage with data from NHS Digital up until Dec 31, 2015. The key outcomes were mortality after presentation to hospital for self-harm, categorised into suicide, accidental deaths, and death by other causes. We calculated incidence of suicide since first hospital presentation for self-harm and used Cox proportional hazard models to estimate the associations between risk factors (sex, age, previous self-harm) and suicide., Findings: Between Jan 1, 2000, and Dec 31, 2013, 9303 individuals aged 10-18 years presented to the study hospitals. 130 individuals were excluded because they could not be traced on the national mortality register or had missing data on sex or age, thus the resulting study sample consisted of 9173 individuals who had 13 175 presentations for self-harm. By the end of the follow-up on Dec 31, 2015, 124 (1%) of 9173 individuals had died. 55 (44%) of 124 deaths were suicides, 27 (22%) accidental, and 42 (34%) due to other causes. Of the 9173 individuals who presented for self-harm, 55 (0·6%) died by suicide. Most suicide deaths involved self-injury (45 [82%] of 55 deaths). Switching of method between self-harm and suicide was common, especially from self-poisoning to hanging or asphyxiation. The 12-month incidence of suicide in this cohort was more than 30 times higher than the expected rate in the general population of individuals aged 10-18 years in England (standardised mortality ratio 31·0, 95% CI 15·5-61·9). 42 (76%) of 55 suicides occurred after age 18 years and the annual incidence remained similar during more than 10 years of follow-up. Increased suicide risk was associated with male sex (adjusted hazard ratio 2·50, 95% CI 1·46-4·26), being an older adolescent at presentation to hospital for self-harm (1·82, 0·93-3·54), use of self-injury for self-harm (2·11, 1·17-3·81; especially hanging or asphyxiation [4·90, 1·47-16·39]), and repeated self-harm (1·87, 1·10-3·20). Accidental poisoning deaths were especially frequent among males compared with females (odds ratio 6·81, 95% CI 2·09-22·15)., Interpretation: Children and adolescents who self-harm have a considerable risk of future suicide, especially males, older adolescents, and those who repeated self-harm. Risk might persist over several years. Switching of method from self-harm to suicide was common, usually from self-poisoning to self-injury (especially hanging or asphyxiation). Self-harm is also associated with risk of death from accidental poisoning, particularly involving drugs of abuse, especially in young males., Funding: UK Department of Health and Social Care., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Self-harm is the strongest risk factor for subsequent suicide, but risk may vary. We compared the risk of suicide following hospital presentation for self-harm according to patient characteristics, method of self-harm, and variations in area-level socioeconomic deprivation, and estimated the incidence of suicide by time after hospital attendance., Methods: In this ongoing Multicentre Study of Self-harm in England, the study population consists of individuals aged at least 15 years who had attended the emergency department of five general hospitals in Oxford, Manchester, and Derby after non-fatal self-harm between Jan 1, 2000, and Dec 31, 2013. Information on method of self-harm was obtained through systematic monitoring in hospitals. Level of socioeconomic deprivation was based on the Index of Multiple Deprivation (IMD) characterising the area where patients lived, grouping them according to IMD quintiles. Mortality follow-up was up to Dec 31, 2015, resulting in up to 16 years of follow-up. We calculated incidence of suicide since first hospital presentation by follow-up period and estimated the association between individual factors (age, gender, method of self-harm, IMD, and number of non-fatal self-harm presentations to hospital) and suicide using mixed-effect models., Findings: Between Jan 1, 2000, and Dec 31, 2013, there were 92 177 presentations to the study hospitals by 51 108 individuals. 1325 patients involved in 1563 self-harm episodes were excluded from the study because they had missing information on gender, age, or mortality. The resulting study sample consisted of 90 614 hospital presentations by 49 783 individuals. By the end of follow-up on Dec 31, 2015, 703 patients had died by suicide. The overall incidence of suicide was 163·1 (95% CI 151·5-175·6) per 100 000 person-years, and 260·0 (237·4-284·8) per 100 000 person-years in men and 94·6 (83·3-107·4) per 100 000 person-years in women. The incidence of suicide was highest in the year following discharge from hospital (511·1 [451·7-578·2] per 100 000 person-years), particularly in the first month (1787·1 [1423·0-2244·4] per 100 000 person-years). Based on all presentations to hospital, men were three times more likely than women to die by suicide after self-harm (OR 3·36 [95% CI 2·77-4·08], p<0·0001). Age was positively related to suicide risk in both genders, with a 3% increase in risk for every one-year increase in age at hospital presentation (OR 1·03 [1·03-1·04], p<0·0001). Relative to hospital presentations after self-poisoning alone, presentations involving both self-injury and self-poisoning were associated with higher suicide risk (adjusted OR 2·06 [95% CI 1·42-2·99], p<0·0001], as were presentations after self-injury alone (adjusted OR 1·36 [1·09-1·70], p=0·007). Similarly, relative to self-harm by self-poisoning alone, attempted hanging or asphyxiation (adjusted OR 2·70 [1·53-4·78], p=0·001) and traffic-related acts of self-injury (adjusted OR 2·99 [1·17-7·65], p=0·022) were associated with greater risk of suicide. Self-cutting combined with self-poisoning was also associated with increased suicide risk (adjusted OR 1·36, [1·08-1·71], p=0·01). Compared with those patients living in the most deprived areas, those who lived in the least deprived areas (first national IMD quintile) had a greater risk of dying by suicide (adjusted OR 1·76 [1·32-2·34], p<0·0001) after adjusting for gender, age, previous self-harm, and psychiatric treatment, as did those living in the second least deprived areas (adjusted OR 1·64 [1·20-2·25], p=0·002)., Interpretation: Patients attending hospital for self-harm are at high risk of suicide, especially immediately after hospital attendance. Certain patient characteristics and methods of self-harm, together with living in areas of low socioeconomic deprivation, can increase patients' subsequent suicide risk. However, while specific risk factors can be usefully integrated into the assessment process, individual factors have poor utility in predicting suicide, so the needs and risks of all patients should be assessed to develop appropriate aftercare plan, including early follow-up., Funding: UK Department of Health and Social Care., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Inhibition of pregnancy-associated plasma protein-A (PAPP-A), an upstream activator of the insulin-like growth factor (IGF) pathway, is known to augment sensitivity to platinum-based chemotherapy. This study further tests the efficacy of PAPP-A inhibition with a monoclonal antibody inhibitor (mAb-PA) in ovarian cancer (OC) platinum-resistant patient-derived xenograft (PDX) models., Methods: PAPP-A expression was quantitated in platinum-resistant PDX models by ELISA. A subset with High (n = 5) and Low (n = 2) expression were revived in female SCID/beige mice for studies with either saline, carboplatin/paclitaxel (CP) + mAb-PA, or CP + IgG2a. The primary endpoint was tumor area by ultrasound on day 28 relative to baseline. Conversion to platinum-sensitive was defined by average tumor regression below baseline. Statistical analyses included linear mixed effects modeling and Kaplan Meier curves. Response to therapy was correlated with changes in the ratio of phosphorylated/total AKT and ERK 1/2 using Wes analysis., Results: The addition of mAb-PA to CP induced tumor regression below baseline in one High PAPP-A PDX model; another three models exhibited notable growth inhibition relative to CP + IgG2a. None of the Low PAPP-A PDX models regressed below baseline. The PDX model with the greatest magnitude of tumor regression from baseline after combination therapy was maintained on single agent mAb-PA or IgG2a, but no benefit was observed. Decreased phosphorylation of ERK1/2 correlated with conversion to platinum-sensitive., Conclusions: The addition of mAb-PA to CP overcame platinum-resistance in one of five High PAPP-A PDX models; three other models demonstrated improved platinum-response. This supports further clinical development of this novel therapeutic., Competing Interests: Dr. Cheryl A. Conover holds a patent(US 8,653,020) on the monoclonal antibody which can selective exosite inhibition of PAPP-A activity against IGFBP-4). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Nursing students and registered nurses often feel underprepared for their roles in dementia care. Extracurricular activities offer nursing students additional opportunities for professional development. A student-academic partnership initiative was developed in which nursing students delivered dementia friends sessions to their peers before formal taught content., Aim: To explore dementia champion nursing students' experiences, identify factors that affect collaborative working and make recommendations for future student-academic partnership projects., Method: In individual and dual interviews, three students were asked about their experiences of participating in the initiative. Interviews were recorded, transcribed and analysed using a thematic analysis framework., Findings: Four themes were identified: commitment to working with people who have dementia, difficulties in taking on extracurricular responsibilities, personal development, and relationships and collaboration., Conclusion: Students were motivated by the need to provide high-quality dementia care. They identified benefits of collaborative working including development of time management, team working, leadership, communication and presentation skills. Future projects should take into account student workloads and offer rewards that are congruent with nursing students' values., Competing Interests: The study was funded by Birmingham City University, England, (© 2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Digital neural loops are present in the palms of most individuals. They can arise within the common palmar digital nerves (CPDNs) or proper palmar digital nerves (PPDNs). Typically, common palmar digital arteries (CPDAs) pass through digital neural loops, however there are reports of loops forming around the superficial palmar arch or proper palmar digital arteries (PPDAs). We describe an unusual digital neural loop that involved both a CPDN and a PPDN. To our knowledge, this is the first documented case of a digital neural loop of this type and therefore anatomists and surgeons may benefit from an awareness of its existence. A modification to a current classification system for digital neural loops is presented to include this novel loop. Interestingly, the cadaver documented in this report featured a high division of the median nerve in each forearm. On both sides, the ulnar component of the bifid median nerve followed an intramuscular course in which it pierced the flexor digitorum superficialis and then continued into the palm as the 3rd CPDN. A brief review of the literature is provided for both digital neural loops and the high division of the median nerve variant. Documented muscle associations noteworthy to the bifid median nerve are discussed. Developmental connections, if any, that exist between the unique digital neural loop and the high division of the median nerve are not speculated upon.

Background: Self-harm is a major healthcare problem and changes in its prevalence and characteristics can have important implications for clinical services, treatment and prevention., Methods: We analysed data on all self-harm presentations to the general hospital in Oxford between 1996 and 2010 using the Oxford Monitoring System for Self-harm. We investigated trends in prevalence, methods and repetition of self-harm, and receipt of psychosocial assessment. For patients receiving a psychosocial assessment, we investigated trends in alcohol use and misuse, prior psychiatric treatment and self-harm, problems, and suicidal intent., Results: Rates of self-harm rose in both genders between 1996 and 2002/2003, after which they declined. There was evidence of a possible cohort effect, whereby higher rates in younger males in earlier years transferred over time to older age groups. Self-cutting, hanging and jumping became more common. Paracetamol was involved in 44.9 % of all self-poisoning episodes. Overdoses of antidepressants (particularly selective serotonin reuptake inhibitors) increased, as did those of mood stabilisers, non-opiate analgesics excluding paracetamol (e.g. non-steroidal anti-inflammatory drugs), and non-ingestible poisons. Alcohol use in relation to self-harm and alcohol-related problems became more common, as did history of prior psychiatric treatment and, especially, of self-harm, and employment problems from 2008. Despite national guidance, the proportion of patients undergoing psychosocial assessment declined., Conclusions: Major changes in the extent and nature of self-harm occurred over the study period, some suggestive of increased psychopathology and others reflecting prescribing practices and changes in drinking patterns. The findings emphasise the need for psychosocial assessment following self-harm, to identify treatment needs and reduce repetition.

The purpose of this study was to ascertain if prophylactic ingestion of a diet rich in vitamin E would prevent or impede the development of ulcerative dermatitis in mice on a C57BL/6 background. Mice were fed either a standard mouse diet, vitamin E (99 IU/kg), or a mouse diet fortified with vitamin E (3000 IU/kg) after weaning. Cases of ulcerative dermatitis were recorded by individuals unmasked to the diet assignment. The incidence of ulcerative dermatitis in a retrospective cohort of mice on standard diet was compared with the group on the diet fortified with vitamin E. Age was associated with ulcerative dermatitis in standard diet and vitamin E fortified diet groups, r = 0.43, p-value < 0.0001 and r = 0.18, p-value < 0.02, respectively. The average age of incidence for ulcerative dermatitis in the mice fed the standard diet was 89 weeks and for the mice fed the vitamin E diet it was 41 weeks. The unadjusted odds ratio comparing the incidence of ulcerative dermatitis between the two diet groups was 4.6 with a 95% confidence interval of (2.44, 8.58), χ(2) p-value < 0.0001. Therefore, there was an association between the diets and ulcerative dermatitis, with the mice on the vitamin E fortified diet having almost five times the odds of having ulcerative dermatitis compared with mice on the standard diet. Incidence of ulcerative dermatitis was not influenced by sex or genotype. Our study results show that a diet fortified in vitamin E initiated at weaning does not prevent or impede the development of ulcerative dermatitis in mice on a C57BL/6 background and may accelerate development when administered to young mice.

Aim: To identify lifestyle factors affecting risk of relapse., Methods: A comparison of 131 relapsed melanoma patients with 147 non-relapsers., Results: Relapsers were more likely to report financial hardship using a number of different measures including access to holidays and feeling financially insecure (odds ratio (OR) 5.7, 95% confidence interval (CI) (1.5, 21.4)). Relapsers worked longer hours (mean 37h per week compared with 31, p=0.02). There was no reported difference in stress associated with recent life events. There was no effect of housing quality, employment factors or body mass index (BMI) on risk of relapse. There was a protective effect of antibiotics in the peri-operative period., Conclusion: The study provides preliminary evidence for adverse effects of chronic financial hardship, but not recent stressful events on cancer relapse. As these data were collected in a retrospective case-control study subject to recall bias, the data must now be explored in a prospective study.

Monitoring of deliberate self-harm (DSH) presentations to hospitals (and in other settings) is receiving increased attention in many countries. This is due to greater recognition of the size of the problem and awareness of its relevance to suicide prevention policy initiatives, because of the strong association between DSH and suicide. A system for monitoring all DSH presentations has been in place in the general hospital in Oxford for 30 years. Based on our experience, in this paper we describe procedures for monitoring, including case definition and identification, linkage of persons and episodes in order to investigate repetition of DSH and other outcomes (including deaths), and data protection and ethical issues. We also provide details of how to carry out monitoring, including different models of data collection, and what data to collect. Finally we consider the potential uses of the data for both clinical and research purposes, including evaluation of national suicide prevention initiatives.

Background: Deliberate self-harm (DSH) is a major healthcare problem in adolescents. Identification of targets for prevention and treatment requires ongoing monitoring of trends and characteristics of those involved., Method: Using data from the Oxford Monitoring System for Attempted Suicide, we have examined trends and characteristics in adolescents aged 12-18 years presenting to a general hospital because of DSH between 1990 and 2000., Results: The numbers of presentations by females increased during the study period. An association of DSH with school stress was suggested by there being fewer presentations during the school holiday periods, the largest number in term times occurring on Mondays, and study problems being common. Self-poisoning was involved in more than 90% of episodes. Paracetamol overdoses decreased following legislation on pack sizes of analgesics. Antidepressant overdoses increased during the study period, in keeping with the rise in prescriptions. Drug misuse increased markedly in the boys, as did a history of violence to others. Being a victim of violence increased in girls. Suicide intent was higher in males. Problems faced by the adolescents showed marked gender differences, and differed between age groups and between those carrying out their first DSH episode and repeaters., Conclusions: Clinical management of DSH in adolescents requires a range of responses, often involving multiservice and multidisciplinary input. Preventive initiatives in schools are also required.

Insulin-like growth factors (IGFs) are one of the most potent stimulators of cell growth. IGFs are modulated by six high affinity binding proteins (IGFBPs) which are, in turn, regulated through post-translational modifications such as proteolysis. In the conditioned media of human fibroblasts, IGFBP-4 is cleaved by an apparently novel IGFBP-4-specific protease that requires IGF for functional activity. We have used several biochemical manipulations, including size exclusion chromatography, native gel electrophoresis, chaotropic salt precipitation, hydrophobic interaction chromatography, ion exchange chromatography, isoelectric focusing, lectin affinity chromatography, and metal chelating affinity chromatography to both characterize and partially purify the IGF-dependent IGFBP-4 protease. Our results indicate that this protease is a highly glycosylated, Zn+2 binding metalloprotease with a native molecular weight greater than 200 kDa.

We previously reported that preexposure of cultured bovine fibroblasts to insulin at low concentrations inhibits subsequent insulin-like growth factor I (IGF-I)-stimulated DNA synthesis. This insulin-induced desensitization to IGF-I is mediated by specific insulin receptors on bovine fibroblasts and occurs distally to IGF-I receptor engagement and activation. In the present study, we use this model system to determine insulin and IGF-I receptor interplay in the regulation of proto-oncogenes involved in mitogenesis. Insulin (10 nM), IGF-I (10 nM), and 10% fetal bovine serum were each capable of stimulating rapid and transient c-fos and c-myc mRNA expression in bovine fibroblasts. Expression of c-myc was most responsive to mitogenic stimuli; IGF-I and serum had equivalent potency resulting in approximately 14-fold increases in c-myc mRNA expression, while insulin produced 3- to 5-fold increases. Max mRNA, which encodes the partner protein for Myc, was constitutively expressed and levels did not change with treatment or with time. When bovine fibroblasts were pretreated with 10 nM insulin for 48 h, washed, and then stimulated with 10 nM IGF-I, alterations in c-fos mRNA expression were moderate. In contrast, insulin pretreatment completely blocked IGF-I induction of c-myc expression. This block was averted if a specific inhibitor of intracellular signaling through the phosphatidylinositol 3-kinase pathway was present during the incubation period with insulin. These data indicate significant insulin/IGF-I receptor interplay in normal bovine fibroblasts and suggest that insulin receptor-initiated signaling can profoundly alter proto-oncogene expression induced by growth factors sharing components of a common intracellular signaling network.