An artificial intelligence deep learning model for identification of small bowel obstruction on plain abdominal radiographs.

OBJECTIVES: Small bowel obstruction is a common surgical emergency which can lead to bowel necrosis, perforation and death. Plain abdominal X-rays are frequently used as a first-line test but the availability of immediate expert radiological review is variable. The aim was to investigate the feasibility of using a deep learning model for automated identification of small bowel obstruction. METHODS: A total of 990 plain abdominal radiographs were collected, 445 with normal findings and 445 demonstrating small bowel obstruction. The images were labelled using the radiology reports, subsequent CT scans, surgical operation notes and enhanced radiological review. The data were used to develop a predictive model comprising an ensemble of five convolutional neural networks trained using transfer learning. RESULTS: The performance of the model was excellent with an area under the receiver operator curve (AUC) of 0.961, corresponding to sensitivity and specificity of 91 and 93% respectively. CONCLUSION: Deep learning can be used to identify small bowel obstruction on plain radiographs with a high degree of accuracy. A system such as this could be used to alert clinicians to the presence of urgent findings with the potential for expedited clinical review and improved patient outcomes. ADVANCES IN KNOWLEDGE: This paper describes a novel labelling method using composite clinical follow-up and demonstrates that ensemble models can be used effectively in medical imaging tasks. It also provides evidence that deep learning methods can be used to identify small bowel obstruction with high accuracy.

Sexuality and sexual experiences during gender transition: A thematic synthesis.

AIM: To establish what impact, if any, the gender-affirmation process, has on sexuality and sexual experiences. INTRODUCTION: Sexuality is a multi-faceted construct that influences our attraction to others. Gender transition is the process of aligning our physical sex characteristics with our psychological gender. Our sexuality and our gender identity are often mistakenly assumed to be inextricably linked. It is important to consider and understand the influence of the gender-affirmation process on sexuality and sexual experiences. METHOD: A thematic synthesis of the available qualitative literature regarding sexuality, and sexual experiences in both transgender people and their partners were appraised, and synthesised. Thomas and Harden's (2008) stepwise process for conducting a thematic synthesis was followed. RESULTS: A total of seven articles were of relevance and included in the review. Two analytical and six sub-themes were found. The two analytical themes are: 'Re-negotiating previous 'norms" and 'Establishing identity'. CONCLUSION: During the gender-affirmation process, sexuality, and sexual experiences alter. This has clinical implications for transgender people and their partners, in particular, valuable therapeutic discussion points that need to be considered during the gender-affirmation process.

ELIXIR-UK role in bioinformatics training at the national level and across ELIXIR.

ELIXIR-UK is the UK node of ELIXIR, the European infrastructure for life science data. Since its foundation in 2014, ELIXIR-UK has played a leading role in training both within the UK and in the ELIXIR Training Platform, which coordinates and delivers training across all ELIXIR members. ELIXIR-UK contributes to the Training Platform's coordination and supports the development of training to address key skill gaps amongst UK scientists. As part of this work it acts as a conduit for nationally-important bioinformatics training resources to promote their activities to the ELIXIR community. ELIXIR-UK also leads ELIXIR's flagship Training Portal, TeSS, which collects information about a diverse range of training and makes it easily accessible to the community. ELIXIR-UK also works with others to provide key digital skills training, partnering with the Software Sustainability Institute to provide Software Carpentry training to the ELIXIR community and to establish the Data Carpentry initiative, and taking a lead role amongst national stakeholders to deliver the StaTS project - a coordinated effort to drive engagement with training in statistics.

Exploring overweight and obesity in pre-school children using routinely collected data: a case study of Halton, Northwest England.

BACKGROUND: A growing body of evidence suggests that childhood overweight may have its roots in early life. This study aimed to explore patterns of weight in children from birth to 40 months, born between 1994 and 2006, in Halton, Northwest England. METHODS: Halton infants were compared with the UK-90 reference population at four time points (birth, 2 months, 8 months and 40 months) by converting heights and weights into age-sex adjusted SD scores. The mean and SD of Halton SD scores were calculated for each time point and sex. Cohort trends and gender differences in rates of children above the 85th and 95th centiles at each time point were tested for using Poisson regression modelling. RESULTS: A total of 16 381 births were analysed. At birth, 8 months and 40 months, proportions of Halton children above the 85th and 95th centiles were consistently higher than reference data. Proportions above the 85th and 95th centiles at birth did not change significantly year on year, but for all other time points the proportions increased with subsequent cohorts. CONCLUSIONS: This study may provide evidence that the development of overweight and obesity has its roots in very early life and has highlighted patterns of infant overweight and obesity not previously reported.

Fruit and vegetables on prescription: a brief intervention in primary care.

BACKGROUND: Increasing fruit and vegetable consumption is a goal for the U.K. Therefore, the effectiveness of a fruit and vegetable voucher scheme coupled with key 'five-a-day' consumption messages as a brief intervention in primary care consultations was assessed in the present study. METHODS: One thousand one hundred and eighty-eight vouchers as a prescription for fruits and vegetables were routinely distributed to patients attending a primary healthcare centre in a deprived area, and 124 volunteer patients routinely attending the centre were included. Telephone-based questionnaires were used to examine changes in consumption over the short and medium term. Other key aspects assessed in the evaluation related to fruit and vegetable purchasing behaviour, knowledge relating to what constitutes a portion size, the relationship between food and health, and barriers to consumption. RESULTS: Although 76.2% of participants used the prescription vouchers when purchasing fruits and vegetables, a significant change in the consumption or purchasing behaviour was not observed (P > 0.05). Participants' level of knowledge relating to the number of portions recommended and the portion size of different fruits and vegetables showed a moderate increase from baseline over the short and medium term. The primary barriers to fruit and vegetable consumption were reported as 'the quality of fresh fruits and vegetables' and 'the money available to spend on food'. CONCLUSIONS: The use of 'the fruit and vegetable on prescription' scheme was an effective method of engaging participants in improving awareness of key diet-related health messages. However, further intervention is required to produce a significant impact on the actual behaviour change.

An assessment of the impact of home safety assessments on fires and fire-related injuries: a case study of Cheshire Fire and Rescue Service.

BACKGROUND: Deaths and injuries related to fires are largely preventable events. In the UK, a plethora of community-based fire safety initiatives have been introduced over the last 25 years, often led by fire and rescue services, to address this issue. This paper focuses on one such initiative--home safety assessments (HSAs). Cheshire Fire and Rescue Service (in England) implemented a uniquely large-scale HSA intervention. This paper assesses its effectiveness. METHODS: The impact of HSAs was assessed in relation to three outcomes: accidental dwelling fires (ADFs), ADFs contained and injuries arising from ADFs. A two-period comparison in fire-related rates of incidences in Cheshire between 2002 and 2011 was implemented, using Poisson regression and adjusting for the national temporal trend using a control group comprising the 37 other English non-metropolitan fire-services. RESULTS: Significant reductions were observed in rates of ADFs [incidence rate ratios (IRR): 0.79, 95% confidence interval (CI): 0.74-0.83, P < 0.001, 2002/03-2007/08 versus 2008/09-2010/11] and associated injuries (IRR: 0.49, 95% CI: 0.39-0.60, P < 0.001, 2002/03-2006/07 versus 2007/08-2010/11), but not in the proportion of fires contained to room of origin. CONCLUSIONS: There is strong evidence to suggest that the intervention was successful in reducing domestic fires and related injuries.

Meeting the sexual health care needs of young people: a model that works?

INTRODUCTION: In the UK, young people have been identified as a specific group who experience poor sexual health and there is scope for improving this if sexual health services are sensitive and relevant to their needs. This paper reports on the work of two services which were set up specifically for young people, exploring whether the model of service provision adopted was successful in engaging this group. METHODS: Routine monitoring data (anonymous) in relation to all contacts with the services were collected. After the services had become established, short questionnaires were administered to young people using them. RESULTS: For service one, 425 contacts were recorded over 34 service sessions. Of these, 149 were new clients: 52% young men (78) and 48% young women (71), with a mean age of 14 years. There were 259 repeat contacts: 74% with young men (191) and 26% with young women (68). For service two, 399 contacts were recorded over 61 service sessions. Of these, 118 were new clients: 32% young men (38) and 68% young women (80), with a mean age of 16.8 years. There were 274 repeat contacts: 40% with young men (108) and 60% (166) with young women. All of the young people were generally very satisfied with the services they received. The youngest young people were less likely to indicate that they would have accessed other sexual health services. DISCUSSION AND CONCLUSIONS: This study indicates that young people of both sexes, between the ages of 11 and 19 years, can be engaged by sexual health services, if provision is modelled on 'best practice' and what is known about the sexual health service needs of young people. Engagement with such services is a prerequisite for addressing the diversity of sexual health needs young people are likely to have in contemporary society and the findings of this study in relation to gender and age are particularly pertinent.

Mainstreaming prevention: prescribing fruit and vegetables as a brief intervention in primary care.

This paper examines a brief preventive intervention as a model for embedding public health action in primary care. BACKGROUND: Low fruit and vegetable intake is a major risk factor for cancer, coronary heart disease and stroke. The recommended intake of five portions per day would reduce death rates from these causes by 20%. However, average daily consumption in the UK is under three portions, and it is significantly lower in men, young people and lower socio-economic groups. In order to tackle risk factors such as poor diet, the white paper Choosing Health promises action and funding to mainstream prevention and transform the NHS from a sickness service to a genuine health service. THE INTERVENTION: To promote increased fruit and vegetable consumption, primary care professionals working in a deprived area issue prescriptions which offer the patient discounts on fruit and vegetable purchases. Hand over of each prescription to the patient is linked explicitly to key five a day messages. This brief intervention takes 1-2 min to deploy. IMMEDIATE OUTCOMES: Evaluation is ongoing. However, early feedback suggests that the intervention of prescription plus key messages has a significant impact on patients in highlighting the connection between food and health. Clinicians express satisfaction at having a preventive intervention that can be deployed with confidence and consistency in routine primary care consultations. DISCUSSION: This brief intervention is presented as a potential model for embedding prevention in the day-to-day work of health professionals. Primary care is a natural setting for the promotion of health, but despite success in implementing some public health programmes, it has a patchy record in primary prevention. The reasons for this are examined, the impact of new contractual and commissioning levers is explored, and a general framework for mainstreaming public health action in primary care is proposed.

Collaborative community-based research and innovation.

This work describes the results and lessons learned from a community-academic partnership to research the effect of training on the capacity of rural home care aides to care for older persons with dementia. The research study increased the aides' knowledge of Alzheimer's and related disorders and, for one group, the aides' satisfaction. The authors used content analysis to identify barriers and facilitators of success of the research partnership. These factors are discussed and placed within a framework of innovation concepts.

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. OBJECTIVES: This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. METHODS: This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. RESULTS: A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. CONCLUSIONS: 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group.

OBJECTIVE: To test the reliability of the eczema area and severity index (EASI) scoring system by assessing inter- and intra-observer consistency. DESIGN: Training of evaluators, application, and assessment over 2 consecutive days. SETTING: An academic center. PATIENTS: Twenty adults and children with atopic dermatitis (AD); cohort 1 (10 patients > or = 8 years) and cohort 2 (10 patients < 8 years). INTERVENTIONS: None. MAIN OUTCOME MEASURE: The EASI was used by 15 dermatologist evaluators to assess atopic dermatitis in cohort 1 and cohort 2 on 2 consecutive days. Inter- and intraobserver reliability were analyzed. RESULTS: Overall intra-evaluator reliability of the EASI was in the fair-to-good range. Inter-evaluator reliability analyses indicated that the evaluators assessed the patients consistently across both study days. CONCLUSIONS: This study demonstrated that the EASI can be learned quickly and utilized reliably in the assessment of severity and extent of AD. There was consistency among the evaluators between consecutive days of evaluation. These results support the use of the EASI in clinical trials of therapeutic agents for AD.

Intraoperative radioimmunodetection.

The radioimmunoguided surgery (RIGS) system employs a monoclonal antibody (CC49), a radionuclide (Iodine-125), and a hand-held gamma-detecting probe (the Neoprobe model 1000). The prototype cancer studied has been colorectal cancer. The antibody identifies a type of mucin, the by-product of the adenocarcinoma cancer cell. The RIGS system localizes up to 90% of colorectal cancers and finds additional RIGS-positive tissues in >50% of the patients. More than 90% of the RIGS-positive visceral tumors are identified by routine hematoxylin-and-eosin (H&E) light microscopy, but the RIGS-positive lymph nodes are H&E occult tissues in >70% of the cases. Enhanced, more time-consuming methods have been developed to confirm hidden cancer cells in these lymph node tissues. Survival data confirm the importance of RIGS-positive tissues. RIGS-positive tissues remaining at the completion of the surgical procedure portend a much poorer outcome than if the patient is deemed RIGS-negative at the completion of the surgical procedure (i.e., all RIGS-positive tissue was removed at surgery).

Effectiveness of the ascomycin macrolactam SDZ ASM 981 in the topical treatment of atopic dermatitis.

OBJECTIVE: To compare the safety and efficacy of 1% SDZ ASM 981 cream and a matching placebo cream in the treatment of patients with moderate atopic dermatitis. DESIGN: A randomized, double-blind, placebo-controlled, right-and-left comparison study. SETTING: Academic referral center. PATIENTS: Thirty-four adult patients with moderate atopic dermatitis. INTERVENTION: Topical 1% SDZ ASM 981 cream was applied twice daily (n=16) or once daily (n=18) and compared with a corresponding placebo cream base. MAIN OUTCOME MEASURES: Efficacy was measured using a 4-point (0-3) scale for erythema, pruritus, exudation, excoriation, and lichenification (Atopic Dermatitis Severity Index [ADSI]). The ADSI score was defined as the sum of these 5 ratings (range, 0-15) and was determined on the pretreatment day (1 to 14 days before day 0) and on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. The percentage change from baseline (day 0) in the ADSI score was calculated on each of these days. Safety was evaluated by monitoring of adverse events, physical examination, hematologic examination, clinical chemistry studies, urinalysis, and measurement of blood levels of SDZ ASM 981. RESULTS: Of the 38 patients recruited, 34 started and 28 completed treatment according to the protocol. Sixteen patients used the cream twice daily, with significant improvement after 2 days of treatment. Within 3 weeks of topical therapy with 1% SDZ ASM 981 cream twice daily, a mean reduction of 71.9% in the ADSI score was observed at the actively treated test sites compared with a mean reduction of 10.3% at the placebo-treated test sites (P<.001). Efficacy was significantly less in the group treated once daily (n=18), with mean reductions of 37.7% and 6.2%, respectively. The efficacy was especially apparent for pruritus and excoriation. There were no clinically relevant drug-related adverse effects. CONCLUSIONS: Treatment with 1% SDZ ASM 981 cream was well tolerated. Twice-daily application of 1% SDZ ASM 981 cream was significantly more effective than use of the corresponding placebo and more effective than once-daily treatment. The new macrolactam ascomycin derivative SDZ ASM 981 is a promising agent for the treatment of patients with atopic dermatitis. More elaborate phase 2 and 3 trials are under way to fully investigate the potential of this medication.

The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis when used topically under occlusion.

Topical SDZ ASM 981 has been found to be highly effective in preclinical models of T-cell-mediated skin disease. T cell activation is crucial in the pathogenesis of psoriasis. It has been hypothesized that SDZ ASM 981 may prove to be an effective treatment for chronic plaque psoriasis. Therefore, the study objective was to determine the efficacy, tolerability and safety of the new topical macrolactam, SDZ ASM 981, for chronic plaque psoriasis. Ten patients with chronic plaque-type psoriasis were treated with SDZ ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and open-labelled clobetasol-17-propionate ointment (0.05%) in a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that, after 2 weeks of treatment, total scores described by 92% for clobetasol, by 82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the ointment base (placebo). No adverse drug effects were seen in any patient throughout the study. We conclude from our results that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol-17-propionate (0.05%) in plaque-type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay.

Genomic regions regulating imprinting and insulin-like growth factor-II promoter 3 activity in transgenics: novel enhancer and silencer elements.

Transgenic lines (89) were made with constructs containing eight different combinations of candidate regulatory elements from the insulin-like growth factor-II (Igf2)-H19 region of mouse chromosome 7. In all constructs, promoter 3 of Igf2 was attached to a firefly luciferase reporter gene. Promoter 3 was the common element that imposed a decrease in reporter activity similar to that of endogenous Igf2 after birth. The specific activity of the reporter was measured on the day of birth in the liver and the brain, after each transgene had been transmitted by either the father or the mother. This procedure demonstrated that the quantity and organ distribution of expression from this promoter can be regulated by each element. The following new information was obtained. (a) The 5' differentially methylated region of Igf2 inhibits promoter 3 in the liver. (b) The conserved DNase I-hypersensitive Middle region between Igf2 and H19 is an enhancer of promoter 3 in the brain. (c) The H19 promoter inhibits Igf2 promoter 3 in the brain. The results confirmed that the H19 enhancer is a strong enhancer of promoter 3 in the liver. A new finding was that one genomic region regularly imposed imprinted gene expression. This was the H19 enhancer, and this region was sufficient to give higher expression on maternal transmission in the majority of transgenic lines. The full data are reported in Supplementary Publication SUP 50180 (8 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1997) 21, 8-10.

Pharmacokinetics of iodine-125 CC49 monoclonal antibody in patients with colon cancer.

UNLABELLED: Radioimmunoguided Surgery techniques which use radiolabeled tumor specific markers and an intraoperative detector in an attempt to improve therapy and survival in patients with cancer have been under development for over fifteen years. Monoclonal antibody (MAb) CC49 is a second-generation murine IgG1 which has improved localization properties over its predecessor, MAb B72.3, and has been studied in a number of patients. In order to determine the pharmacokinetics of iodine-125 (125I) CC49 MAb, size-exclusion, high-performance liquid chromatography (HPLC) was used to assess radioactive components in serum and urine following administration of the drug to colon cancer patients. METHODS: Five patients received an intravenous infusion of 10 mg of MAb CC49 labeled with 2 mCi 125I. Following infusion, serum and urine specimens were collected from patients at predetermined time intervals prior to surgery. HPLC analysis of these specimens was completed to determine the radioactive species in each sample. RESULTS: Serum and urine specimens showed that serum levels of CC49 decrease exponentially and become unmeasurable by day 14 (half-life 1.89 days, +/- 0.19), with a steady, low-level of free 125I measurable in postinjection serum until day 21 after infusion. There was no evidence of MAb fragmentation or antibody:antigen (Ab:Ag) complex formation in serum, and no evidence of whole MAb, F(ab')2, or Fab fragment excretion in urine. Preinjection sera with MAb added in vitro also failed to demonstrate Ab:Ag complex formation. Analysis of urine showed low level excretion of free 125I which peaked by day 1 and declined exponentially through day 21, with a very low molecular weight (< 1 kDa) MAb fragment excreted in urine between 1 and 21 days. CONCLUSION: Radioiodinated 125I CC49 MAb remains in serum of cancer patients approximately 14 days, and tissue radioactivity beyond this time may reflect tissue sequestered MAb and/or free 125I and not "bloo pool" radioactivity. CC49 MAb appears to be deiodinated in small but significant quantities before it is metabolized, and clearance of radioactivity is mainly in free 125I form in urine. Measurable quantities of a < 1 Kda MAb fragment in urine and not serum may suggest a renal mechanism of MAb metabolism, but may also represent a metabolic end product of MAb metabolism with a very short serum half-life (T1/2) which accumulates in urine.

Surgical applications of gamma-detecting probes.

The RIGS system is a technology which was developed to provide a more sensitive and accurate method of detecting colorectal cancer during surgery. One of the components of this system is the hand-held, gamma-detecting probe [Neoprobe Model 1000instrument; Neoprobe Corporation, Dublin, Ohio), used by the surgeon to identify preadministered, radiolabeled monoclonal antibody which has localized to dis- eased tissue. RIGSuses sound-directed gamma detection to identify and locate cancer which may not be seen or felt by the surgeon. The success of RIGS has been largely due to the remarkable sensitivity of the gamma- detecting probe in detecting small amounts oflow-energy radioactivity. This attribute has led to the use of the probe for other surgical applications including pre- and intraoperative lymphatic mapping, and parathyroid localization. Surgery for melanoma, breast cancer, parathyroid disease, and colorectal cancer has been af- fected by the increased use of the gamma-detecting probe both in clinical trials and practice. This chapter will review the many applications of this new technology.