A randomized controlled trial of a group-based gaze training intervention for children with Developmental Coordination Disorder

The aim of this study was to integrate a gaze training intervention (i.e., quiet eye training; QET) that has been shown to improve the throwing and catching skill of children with Developmental Coordination Disorder (DCD), within an approach (i.e., group therapy) that might alleviate the negative psychosocial impact of these motor skill deficits. Twenty-one children with DCD were split into either QET (8 male 3 female, mean age of 8.6 years (SD = 1.04) or technical training (TT) groups (7 male 3 female, mean age of 8.6 years (SD = 1.84). The TT group were given movement-related instructions via video, relating to the throw and catch phases, while the QET group were also taught to fixate a target location on the wall prior to the throw (QE1) and to track the ball prior to the catch (QE2). Each group partook in a 4-week, group therapy intervention and measurements of QE duration and catching performance were taken before and after training, and at a 6-week delayed retention test. Parental feedback on psychosocial and motor skill outcomes was provided at delayed retention. Children improved their gaze control and catching coordination following QET, compared to TT. Mediation analysis showed that a longer QE aiming duration (QE1) predicted an earlier onset of tracking the ball prior to catching (QE2) which predicted catching success. Parents reported enhanced perceptions of their child’s catching ability and general coordination in the QET group compared to the TT group. All parents reported improvements in their child’s confidence, social skills and predilection for physical activity following the trial. The findings offer initial support for an intervention that practitioners could apply to address deficits in the motor and psychosocial skills of children with DCD

Modelling UK house prices with structural breaks and conditional variance analysis

This paper differs from previous research by examining the existence of structural breaks in the UK regional house prices as well as in the prices of the different property types (flats, terraced, detached and semi-detached houses) in the UK as a whole, motivated by the uncertainty in the UK housing market and various financial events that may lead to structural changes within the housing market. Our paper enhances the conventional unit root tests by allowing for structural breaks, while including structural break tests strengthens our analysis. Our empirical results support the existence of structural breaks in the mean equation in seven out of thirteen regions of the UK as well as in three out of four property types, and in the variance equation in six regions and three property types. In addition, using a multivariate GARCH approach we examine both the behaviour of variances and covariances of the house price returns over time. Our results have significant implications for appropriate economic policy selection and investment management

Development of Trypanosoma cruzi in vitro assays to identify compounds suitable for progression in Chagas’ disease drug discovery

Chagas' disease is responsible for significant mortality and morbidity in Latin America. Current treatments display variable efficacy and have adverse side effects, hence more effective, better tolerated drugs are needed. However, recent efforts have proved unsuccessful with failure of the ergosterol biosynthesis inhibitor posaconazole in phase II clinical trials despite promising in vitro and in vivo studies. The lack of translation between laboratory experiments and clinical outcome is a major issue for further drug discovery efforts. Our goal was to identify cell-based assays that could differentiate current nitro-aromatic drugs nifurtimox and benznidazole from posaconazole. Using a panel of T. cruzi strains including the six major lineages (TcI-VI), we found that strain PAH179 (TcV) was markedly less susceptible to posaconazole in vitro. Determination of parasite doubling and cycling times as well as EdU labelling experiments all indicate that this lack of sensitivity is due to the slow doubling and cycling time of strain PAH179. This is in accordance with ergosterol biosynthesis inhibition by posaconazole leading to critically low ergosterol levels only after multiple rounds of division, and is further supported by the lack of effect of posaconazole on the non-replicative trypomastigote form. A washout experiment with prolonged posaconazole treatment showed that, even for more rapidly replicating strains, this compound cannot clear all parasites, indicative of a heterogeneous parasite population in vitro and potentially the presence of quiescent parasites. Benznidazole in contrast was able to kill all parasites. The work presented here shows clear differentiation between the nitro-aromatic drugs and posaconazole in several assays, and suggests that in vitro there may be clinically relevant heterogeneity in the parasite population that can be revealed in long-term washout experiments. Based on these findings we have adjusted our in vitro screening cascade so that only the most promising compounds are progressed to in vivo experiments

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Induction of human ADAMTS-2 gene expression by IL-1 alpha is mediated by a multiple crosstalk of MEK/JNK and PI3K pathways in osteoblast like cells

WOS: 000362305000018PubMed: 26232334Up-regulation of ADAMTS genes with proinflammatory cytokines is important for some pathological conditions such as osteoarthritis (OA) that is a disease based on ECM degradation in cartilage. IL-1 alpha is a proinflammatory cytokine and important both to normal and pathophysiologic conditions in cartilage and bone. Effects of some proinflammatory cytokines such as TNF-alpha and IL-1 beta on the some members of ADAMTS family have been investigated in some chondrocyte tissues or cell lines. However the effect of the IL-1 alpha on the expression of ADAMTS-2 and ADAMTS-3 gene expression in osteoblast like cell lines, remains unclear. Therefore, the aim of this study is to investigate the effect of IL-1 alpha on ADAMTS-2 and ADAMTS-3 gene expression in osteoblast like cells, Saos-2 and MG-63. The present study, for the first time, demonstrated that IL-1 alpha increases ADAMTS-2 and ADAMTS-3 gene expressions in both Saos-2 and MG-63 cells. Having correlation to mRNA induction, the upregulation of ADAMTS-2,-3 protein levels by IL-1 alpha stimulation is also observed. The inhibition studies showed that this upregulation occurred at the level of transcription, and there was no effect of IL-1 alpha on ADAMTS-2 mRNA half-life in Saos-2 cells. Transactivation potential of IL-1 alpha on ADAMTS-2 promoter was investigated by transient transfection assay. Specifically, IL-1 alpha strongly increased -658/+112 and -530/+112 ADAMTS-2 promoter constructs. Further, we analyzed signaling pathways involved in ADAMTS-2 induction. Pathway inhibition studies revealed that this upregulation depends on the activation of MEK, JNK and PI3K pathways. These findings suggested that IL-1 alpha is a strong positive regulator of ADAMTS-2 and ADAMTS-3 expression. These findings would provide novel insight into the pathophysiology of OA. (C) 2015 Published by Elsevier B.V.Scientific and Technological Research Council of Turkey (TUBITAK) [212T200]; Balikesir University Scientific Research Projects Unit (BAP) [2010/39]This work was supported mainly by the Scientific and Technological Research Council of Turkey (TUBITAK) (212T200) and partially by the Balikesir University Scientific Research Projects Unit (BAP) (2010/39). Saos-2 cells were kindly provided by Dr. Kenneth Wann (Cardiff, School of Biosciences, Cardiff UK)