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Background: The prevalence of male obesity is increasing but few men take part in weight loss programmes. We assessed the eff ect of a weight loss and healthy living programme on weight loss in football (soccer) fans. Methods: We did a two-group, pragmatic, randomised controlled trial of 747 male football fans aged 35-65 years with a body-mass index (BMI) of 28 kg/m2 or higher from 13 Scottish professional football clubs. Participants were randomly assigned with SAS (version 9.2, block size 2-9) in a 1:1 ratio, stratifi ed by club, to a weight loss programme delivered by community coaching staff in 12 sessions held every week. The intervention group started a weight loss programme within 3 weeks, and the comparison group were put on a 12 month waiting list. All participants received a weight management booklet. Primary outcome was mean diff erence in weight loss between groups at 12 months, expressed as absolute weight and a percentage of their baseline weight. Primary outcome assessment was masked. Analyses were based on intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN32677491. Findings: 374 men were allocated to the intervention group and 374 to the comparison group. 333 (89%) of the intervention group and 355 (95%) of the comparison group completed 12 month assessments. At 12 months the mean diff erence in weight loss between groups, adjusted for baseline weight and club, was 4.94 kg (95% CI 3.95-5.94) and percentage weight loss, similarly adjusted, was 4.36% (3.64-5.08), both in favour of the intervention (p

Background Craniosynostosis, the premature fusion of the cranial sutures, is the second most common craniofacial malformation. A genetic aetiology can be identified in about 21% of cases, including mutations of TWIST1 that cause Saethre-Chotzen syndrome and are associated with coronal synostosis. By contrast, the cause of non-syndromic craniosynostosis is largely unknown. Methods We undertook exome sequencing of seven individuals with bilateral coronal synostosis, identifying mutations of TCF12 in three samples. We sequenced TCF12 in a further 347 patients with craniosynostosis. We performed mutation testing in extended families and determined the effects of mutations on mRNA expression. We examined the genetic interaction between loss-of-function mutations of Tcf12 and Twist1 in mice. Findings Heterozygous TCF12 mutations were present in 38 of the 347 unrelated patients with craniosynostosis. These included 22 (32%) of 69 with isolated bilateral coronal synostosis, and 14 (10%) of 141 with unilateral coronal synostosis, but none with premature fusion of only the metopic, sagittal, or lambdoid sutures (p −6 ). An additional two patients had either bilateral or right coronal synostosis in addition to sagittal synostosis. 14 cases arose de novo, but vertical transmission was demonstrated in 23 families. 16 mutation-positive individuals (47%) had craniosynostosis or suspicious clinical features, but 19 (53%) of 35 mutation-positive relatives were non-penetrant for craniosynostosis. TCF12 mutations were associated with diminished mRNA expression, indicating haploinsufficiency. With appropriate surgical correction the clinical outcome was usually good; six of 66 individuals had learning disability. Mice doubly heterozygous for Twist1 and Tcf12 mutations had severe bilateral coronal synostosis. Interpretation Mutations of TCF12 are a frequent and specific cause of coronal craniosynostosis; mutation testing is indicated in the assessment of these patients. Genetic interaction of Tcf12 and Twist1 is crucial for coronal suture development. Funding National Institute for Health Research Biomedical Research Centre, Oxford (BRC)/Oxford University Clinical Academic Graduate School (OUCAGS), and Oxfordshire Health Services Research Committee (OHSRC), Oxford Craniofacial Unit Charitable Fund; Thames Valley Comprehensive Local Research Network; The Dutch Center for Translational Molecular Medicine; Carolien Bijl Foundation; US National Institutes for Health; Wellcome Trust.

We report an increased prevalence of renal disease, particularly glomerulonephritis, in Upper Weardale, UK. Silica exposure during fluorspar mining and processing is a likely cause.

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In a double-blind trial oestradiol, oestradiol/testosterone, or placebo implants were assessed for their effects on psychological symptoms in women attending a menopause clinic. After two months, women receiving active treatment scored better than the placebo group on a self-rating scale of distress, on anxiety, and on depression (p less than 0.05). Postmenopausal but not perimenopausal women improved after placebo, and at 4 months the scores in the three groups no longer differed significantly.

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