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ove local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours. FUNDING German Cancer Aid (Deutsche Krebshilfe). BACKGROUND CLEOPATRA was a phase 3 study comparing the efficacy and safety of pertuzumab, trastuzumab, and docetaxel with placebo, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer. In the primary analysis and subsequent reports, progression-free and overall survival were significantly improved in the pertuzumab group compared with the placebo group. Here, we report the end-of-study analysis of CLEOPATRA. METHODS This was a double-blind, randomised, placebo-controlled, phase 3 trial that was done at 204 centres in 25 countries. Eligible patients were 18 years or older, had HER2-positive, metastatic breast cancer, had not received previous chemotherapy or biological treatment for their metastatic disease, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. All study drugs were given intravenously, every 3 weeks. Patients were assigned to receive either pertuzumab or placebo at a loading dose of 840 mg, and 420 mg thereafter; plus trastuzumab at 8 mg/kg lHER2-positive metastatic breast cancer, with the dual blockade of pertuzumab and trastuzumab, with docetaxel, demonstrating an 8-year landmark overall survival rate of 37%. FUNDING F Hoffmann-La Roche and Genentech. BACKGROUND Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS We did an open-label, non-inferiority, randomised (11 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had tonal, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac. © 2020 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.Genomics is a sequence-based informatics science and a three-dimensional-structure-based material science. However, in practice, most genomics researchers utilize sequence-based informatics approaches or three-dimensional-structure-based material science techniques, not both. This division is, at least in part, the result of historical developments rather than a fundamental necessity. The underlying computational tools, experimental techniques, and theoretical models were developed independently. The primary result presented here is a framework for the unification of informatics- and physics-based data associated with DNA, nucleosomes, and chromatin. The framework is based on the mathematical representation of geometrically exact rods and the generalization of DNA basepair step parameters. Olitigaltin manufacturer Data unification enables researchers to integrate computational, experimental, and theoretical approaches for the study of chromatin biology. The framework can be implemented using model-view-controller design principles, existing genome browsers, and existing molecular visualization tools. We developed a minimal, web-based genome dashboard, G-Dash-min, and applied it to two simple examples to demonstrate the usefulness of data unification and proof of concept. Genome dashboards developed using the framework and design principles presented here are extensible and customizable and are therefore more broadly applicable than the examples presented. We expect a number of purpose-specific genome dashboards to emerge as a novel means of investigating structure-function relationships for genomes that range from basepairs to entire chromosomes and for generating, validating, and testing mechanistic hypotheses. Here, we discuss options to reform the EU genetically modified organism (GMO) regulatory framework, to make risk assessment and decision-making more consistent with scientific principles, and to lay the groundwork for international coherence. We discussed the scope and definitions in a previous article and, thus, here we focus on the procedures for risk assessment and risk management. Eating disorders are disabling, deadly, and costly mental disorders that considerably impair physical health and disrupt psychosocial functioning. Disturbed attitudes towards weight, body shape, and eating play a key role in the origin and maintenance of eating disorders. Eating disorders have been increasing over the past 50 years and changes in the food environment have been implicated. All health-care providers should routinely enquire about eating habits as a component of overall health assessment. Six main feeding and eating disorders are now recognised in diagnostic systems anorexia nervosa, bulimia nervosa, binge eating disorder, avoidant-restrictive food intake disorder, pica, and rumination disorder. The presentation form of eating disorders might vary for men versus women, for example. As eating disorders are under-researched, there is a great deal of uncertainty as to their pathophysiology, treatment, and management. Future challenges, emerging treatments, and outstanding research questions are addressed. To take the best actions, we often need to maintain and update beliefs about variables that cannot be directly observed. To understand the principles underlying such belief updates, we need tools to uncover subjects' belief dynamics from natural behavior. We tested whether eye movements could be used to infer subjects' beliefs about latent variables using a naturalistic navigation task. Humans and monkeys navigated to a remembered goal location in a virtual environment that provided optic flow but lacked explicit position cues. We observed eye movements that appeared to continuously track the goal location even when no visible target was present there. Accurate goal tracking was associated with improved task performance, and inhibiting eye movements in humans impaired navigation precision. These results suggest that gaze dynamics play a key role in action selection during challenging visuomotor behaviors and may possibly serve as a window into the subject's dynamically evolving internal beliefs. Debate is ongoing regarding when, why, and how to initiate pharmacotherapy for Parkinson's disease. Early initiation of dopaminergic therapies does not convey disease-modifying effects but does reduce disability. Concerns about the development of motor complications arising from the early initiation of levodopa, which led to misconceived levodopa-sparing strategies, have been largely mitigated by the outcomes of the PD MED and Levodopa in Early Parkinson's Disease (LEAP) studies. link2 The LEAP study also showed the potential for early improvement in quality of life, even when disability is negligible. Until more effective methods of providing stable dopamine concentrations are developed, current evidence supports the use of levodopa as initial symptomatic treatment in most patients with Parkinson's disease, starting with low doses and titrating to therapeutic threshold. Monoamine oxidase-B inhibitors and dopamine agonists can be reserved as potential adjunct treatments later in the disease course. Future research will need to establish effective disease-modifying treatments, address whether patients' quality of life is substantially improved with early initiation of treatment rather than a wait and watch strategy, and establish whether new levodopa formulations will delay onset of dyskinesia. Complex regional pain syndrome (CRPS) is a relatively common condition that is often not well recognised or treated adequately. Patients are usually referred to multidisciplinary pain services, but outcomes remain variable. This case report describes a recent patient with CRPS who was treated quickly and effectively through a simple explanation of the relationship between mind and body, and who then was able to modify her own thought processes and behaviours. This single intervention enabled a complete resolution of symptoms. This report illustrates the clinical application of recent insights into neuroplasticity and individually tailored patient self-management that may now offer successful treatment of an otherwise chronic and disabling condition, especially in younger patients. There are implications for doctors in current practice, as well as for the training of medical students and junior doctors.INTRODUCTION Childhood obesity is a major health concern in New Zealand. Primary care nurses have been charged with body mass index (BMI) screening and initiating education or referral of 4-year-old children during the Before School Check (B4SC). Asking nurses about their BMI screening experiences when reporting is mandated by the Ministry of Health reveals valuable knowledge to inform the work of health professionals in this area. link3 AIM To explore the experience of nurses performing the B4SC since the inclusion of the Raising Healthy Kids targets into the wellchild check. METHODS Five focus group discussions across New Zealand were conducted using the Nominal Group Technique. Nurses individually recorded their answers to the research question, 'What is your perception of performing the B4SC since the inclusion of the Raising Healthy Kids target in July 2016?'. Group discussion and establishing priorities followed. Researchers collated and analysed data. Results were obtained by adding up scores across groups to provide the final overall themes of (i) communication; (ii) BMI as a measurement; (iii) cultural norms and socioeconomic situations; (iv) parenting and family structure; and (v) education. RESULTS Communication was the common theme across groups, but other priorities were more specific to the sociodemographic and cultural profile of the areas of practice. Mandatory reporting appears to have had the positive outcome of encouraging nurses to use positive and holistic discussion on health to families rather than concentrating on BMI. Nurses reported using tools to educate parents without implying judgement of their parenting and lifestyle. DISCUSSION Nurses worked hard to maintain relationships with families as they recognised the long-term value of keeping families engaged with health professionals. Where tools were useful, such as the BMI calculator, nurses used these to assist with positive communication. The mandatory nature of the BMI referral had enhanced their skills with difficult conversations.