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Background Children with developmental coordination disorder (DCD) face significant challenges to deal with everyday activities due to underlying motor proficiency difficulties. These challenges affect children and young people’s participation; that is, involvement in daily life situations. A small body of qualitative research  has explored the experiences of children and young people with DCD from their own perspective. Therfore, understanding what it is like to live with DCD is not well conceptualised in the literature. There is a pressing need to synthesise the findings of discrete qualitative studies to advance the conceptual understanding of living with DCD, to inform health service delivery and the development and implementation of complex interventions. Aim This study aims to systematically review and synthesise qualitative literature regarding children and young people’s experiences and views of everyday life and living with DCD. Methods The method of qualitative evidence synthesis that will be followed in this review is a meta-ethnography. The eMERGe and PRISMA reporting guidelines will be adhered to. Ten databases will be searched; Academic Search Complete, AMED, CINAHL, ERIC, MEDLINE, PsychArticles, PsychInfo, EMBASE, SPORTDiscus, and Web of Science. The Joanna Briggs Institute Checklist will be used by two independent reviewers to appraise all included papers. Discussion The findings of this meta-ethnography will endeavour to inform future research, policy and practice. In particular, the results will help to inform the design of future complex interventions to meet the needs of children and young people with DCD. Dissemination will involve the publication of the results in a peer-reviewed journal. Increasingly researchers and policymakers are calling for services to be informed by the perspective and voice of children with DCD. Therefore, a policy brief will be published so that the findings are widely available. Registration: PROSPERO registration number CRD42019129178; registered on 09 July 2019.

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The use of group-based trajectory modelling (GBTM) within the medication adherence literature is rapidly growing. Researchers are adopting enhanced methods to analyse and visualise dynamic behaviours, such as medication adherence, within ‘real-world’ populations. Application of GBTM based on longitudinal adherence behaviour allows for the identification of adherence trajectories or groups.  A group is conceptually thought of a collection of individuals who follow a similar pattern of adherence behaviour over a period of time. A common obstacle faced by researchers when implementing GBTM is deciding on the number of trajectory groups that may exist within a population. Decision-making can introduce subjectivity, as there is no ‘gold standard’ for model selection criteria. This study aims to examine the extent and nature of existing evidence on the application of GBTM for medication adherence assessment, providing an overview of the different GBTM techniques used in the literature. The methodological framework will consist of five stages: i) identify the research question(s); ii) identify relevant studies; iii) select studies; iv) chart the data and finally, v) collate, summarise and report the results. Original peer-reviewed articles, published in English, describing observational and interventional studies including both concepts and/or sub-concepts of GBTM and medication adherence or any other similar terms, will be included. The following databases will be queried: PubMed/MEDLINE; Embase (Ovid); SCOPUS; ISI Web of Science and PsychInfo. This scoping review will utilise the PRISMA extension for Scoping Reviews (PRISMA-ScR) tool to report results. This scoping review will collect and schematise different techniques in the application of GBTM for medication adherence assessment available in the literature to date, identifying research and knowledge gaps in this area. This review can represent an important tool for future research, providing methodological support to researchers carrying out a group-based trajectory analysis to assess medication adherence in a real-world context.

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Background: Schistosomiasis is one of the most prevalent neglected tropical diseases (NTDs) with an estimated 229 million people requiring preventive treatment worldwide. Recommendations for preventive chemotherapy strategies have been made by the World Health Organization (WHO) whereby the frequency of treatment is determined by the settings prevalence. Despite recent progress, many countries still need to scale up treatment and important questions remain regarding optimal control strategies. This paper presents a systematic review of the economic evaluations of human schistosomiasis interventions. Methods: A systematic review of the literature was conducted on 22nd August 2019 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. The focus was economic evaluations of schistosomiasis interventions, such as cost-effectiveness and cost-benefit analyses. No date or language stipulations were applied to the searches. Results: We identified 53 relevant health economic analyses of schistosomiasis interventions. Most studies related to Schistosoma japonicum followed by S. haematobium. Several studies also included other NTDs. In Africa, most studies evaluated preventive chemotherapy, whereas in China they mostly evaluated programmes using a combination of interventions (such as chemotherapy, snail control and health education). There was wide variation in the methodology and epidemiological settings investigated. A range of effectiveness metrics were used by the different studies. Conclusions: Due to the variation across the identified studies, it was not possible to make definitive policy recommendations. Although, in general, the current WHO recommended preventive chemotherapy approach to control schistosomiasis was found to be cost-effective. This finding has important implications for policymakers, advocacy groups and potential funders. However, there are several important inconsistencies and research gaps (such as how the health benefits of interventions are quantified) that need to be addressed to identify the resources required to achieve schistosomiasis control and elimination.

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Background: Sugar is routinely used to comfort neonates undergoing painful procedures, and animal studies have shown that sucrose increases the time to withdrawal from painful stimuli. However, there are no published studies examining the effects of sweet substances on heat pain thresholds and percept in adult humans. Methods: Healthy adult volunteers (n=27, aged 18-48 years) were recruited to a controlled, double-blind, randomised, cross-over study to characterise the effect of tasting solutions of equivalent sweetness (10% sucrose and 0.016% sucralose) on warm detection and heat pain thresholds and the percept ratings of painfully hot stimuli. The effect of anticipation of a sweet taste on heat pain threshold was also assessed. Results: Tasting either sucrose or sucralose had no significant effect on the percept of an individually titrated hot stimulus (54.5±4.2 and 54.9±3.2 vs 53.2±3.5 for water, 0-100 visual analogue scale), on the warm detection or heat pain threshold (43.3±0.8, 43.2±0.8 vs 43.0±0.8°C). Anticipation of a sweet substance similarly did not affect heat pain thresholds. Conclusions: Sucrose and sucralose solutions had no analgesic effect when assessed using heat detection thresholds and percept ratings of painfully hot stimuli despite being perceived as sweeter and more pleasant than water. These findings are in contrast to results reported from previous animal studies in which thermal analgesia from sweet solutions is robust. Given the ubiquitous availability of sugar rich drinks in the modern environment, the lack of observable effect may be due to an insufficient hedonic value of the test solutions when compared to the experience of a laboratory rodent. Alternatively, sweet tastes may have a specific effect on pain tolerance rather than the threshold and acute percept measures assayed in this study.

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Background: The multi-subunit homotypic fusion and vacuole protein sorting (HOPS) membrane-tethering complex is involved in regulating the fusion of late endosomes and autophagosomes with lysosomes in eukaryotes. The C-terminal regions of several HOPS components have been shown to be required for correct complex assembly, including the C-terminal really interesting new gene (RING) zinc finger domains of HOPS components VPS18 and VPS41. We sought to structurally characterise the putative C-terminal zinc finger domain of VPS39, which we hypothesised may be important for binding of VPS39 to cellular partners or to other HOPS components. Methods: We recombinantly expressed, purified and solved the crystal structure of the proposed zinc-binding region of VPS39. Results: In the structure, this region forms an anti-parallel β-hairpin that is incorporated into a homotetrameric eight-stranded β-barrel. However, the fold is stabilised by coordination of zinc ions by residues from the purification tag and an intramolecular disulphide bond between two predicted zinc ligands. Conclusions: We solved the structure of the VPS39 C-terminal domain adopting a non-native fold. Our work highlights the risk of non-native folds when purifying small zinc-containing domains with hexahistidine tags. However, the non-native structure we observe may have implications for rational protein design.

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Lung cancer which represents characteristics of a heavy disease burden, a large proportion of advanced lung cancer and a low five-year survival rate is a threat to human health. It is essential to implement population-based lung cancer screening to improve early detection and early treatment. The National Lung Screening Trial (NLST) demonstrated that screening with low dose helical computed tomography (LDCT) may decrease lung cancer mortality, which brings hope for the early diagnosis and treatment of lung cancer. In recent years, great progresses have been made on research of lung cancer screening with LDCT. However, whether LDCT could be applied to large population-based lung cancer screening projects is still under debate. In this paper, we review the recent progresses on history of lung cancer screening with LDCT, selection of high-risk individuals, management of pulmonary nodules, performance of screening, acceptance of LDCT and cost-effectiveness.
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Metastatic spinal tumors are common, and their rising incidence can be attributed to the expanding aging population and increased survival rates among cancer patients. The decision-making process in the treatment of spinal metastasis requires a multidisciplinary approach that includes medical and radiation oncology, surgery, and rehabilitation. Various decision-making systems have been proposed in the literature in order to estimate survival and suggest appropriate treatment options for patients experiencing spinal metastasis. However, recent advances in treatment modalities for spinal metastasis, such as stereotactic radiosurgery and minimally invasive surgical techniques, have reshaped clinical practices concerning patients with spinal metastasis, making a demand for further improvements on current decision-making systems. In this review, recent improvements in treatment modalities and the evolution of decision-making systems for metastatic spinal tumors are discussed.

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Objective: To compare the effect of hearing improvement after canal wall down mastoidectomy and tympanoplasty(CWDM) and canal wall up mastoidectomy and tympanoplasty(CWUM). Methods: 88 patients who underwent CWDM or CWUM in 2014-2017 with complete follow-up data were retrospectively studied. There were 45 males and 43 females, aged 12-68 years old, and the average follow-up time was 12.3 months. Among them, 42 cases underwent CWDM and 46 cases underwent CWUM. A series of improvements were made in the clinical practice of CWDM: (1) to expand the indications properly, including limited lesions with sclerotic mastoid and narrow tympanic sinus; (2) to form disciform cavity strictly during operation in order to retain the appropriate height of facial nerve crest; (3) to avoid the cleaning of mastoid cavity in the post-operation follow up, thus the operative cavity was effectively constricted; and (4) to transfer the temporal muscle flap in pneumatic mastoid to reduce the cavity. The condition of dry ear and the size of cavity were observed after operation. The average pure tone threshold (PTA) before/after operation and threshold changes of each frequency were compared between the two groups. SPSS 19.0 software was used to analyze the data. Results: The mastoid cavity of CWDM was significantly narrowed after operation and the width of the external auditory canal was close to the CWUM group. The postoperative PTA of the CWDM and CWUM group was reduced by 11.4 dB and 10.4 dB respectively, with no significant difference (t=0.290, P=0.770). The average value of bone conduction threshold after operation was reduced by 1.8 dB and 1.9 dB respectively, with no significant difference (t=-0.076, P=0.940). The mean value of ABG after operation was shortened by 9.6 dB and 8.4 dB respectively, with no significant difference (t=-0.370, P=0.712). The threshold decrease of 1 000 Hz of CWUM was slightly better than that of CWDM, and the threshold decreases of the other frequencies of CWDM were slightly better than those of CWUM, however, the differences were not statistically significant (P>0.05). Conclusion: Through the adjustment of indications and a series of intraoperative and postoperative improvements, CWDM can achieve the same effect of postoperative hearing improvement as CWUM.

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Objective: To explore the possible pathogenesis of central paroxysmal positional vertigo (CPPV) by analyzing its clinical manifestations and characteristics. Methods: The clinical data of 3 patients with CPPV, including 1 male and 2 females, aged 36, 14 and 70 years old respectively, were collected from the Department of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences from June 2014 to June 2018. The clinical symptoms, nystagmus, other central ocular motor abnormalities, MRI, PET-CT, and laboratory findings were analyzed retrospectively. Results: All patients showed transient vertigo and nystagmus induced by head changes relative to gravity, but the characteristics of nystagmus did not conform to the typical characteristics of nystagmus in benign paroxysmal positional vertigo. None of patients response to repositioning maneuvers, and all patients presented with the signs of abnormal visual oculomotor system or other symptoms of central system. MRI, PET-CT and blood biochemical tests confirmed that the causes of CPPV in the patients were chronic hemorrhage, inflammation and paraneoplastic cerebellar degeneration. Although the etiology of the three cases is different, the lesion site is involved in the central velocity storage mechanism. Conclusion: The damage of central velocity storage mechanism may lead to the damage of feedback rotation signal correction pathway, and CPPV appears when the head position changes relative to gravity.