Achieving change in primary care—causes of the evidence to practice gap : systematic reviews of reviews

Acknowledgements The Evidence to Practice Project (SPCR FR4 project number: 122) is funded by the National Institute of Health Research (NIHR) School for Primary Care Research (SPCR). KD is part-funded by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Research and Care West Midlands and by a Knowledge Mobilisation Research Fellowship (KMRF-2014-03-002) from the NIHR. This paper presents independent research funded by the National Institute of Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Funding This study is funded by the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR).Peer reviewedPublisher PD

Undergraduates’ speaking anxiety in English as second language (ESL) classrooms / Kimberley Lau Yih Long ... [et al.]

Many students exhibit fear of speaking in English in the English as Second Language (ESL) classrooms. Additionally, there are limited studies in this area of concern among the undergraduates in Sarawak. Hence, this study aimed to identify the students‟ anxiety level towards speaking English based on four components, namely communication apprehension, test anxiety, fear of negative evaluation, and comfort in using English in the classrooms. This study also examined whether there is any significant difference in the level of anxiety in terms of gender. A total of 592 undergraduates from two public institutions of higher learning in Sarawak were involved in this study. A Public Speaking Class Anxiety Scale (PSCAS) by Yaikhong and Usaha (2012) was adopted in this study to measure anxiety in the ESL speaking classes. The results gathered through the questionnaires were analysed using SPSS package to determine the students‟ speaking anxiety levels and the significant difference in the level of anxiety in speaking English in terms of gender. Thefindings revealed that undergraduates experienced an average level of speaking anxiety. T-test analysis of the findings in the study also portrayed that generally the female undergraduates experienced higher speaking anxiety as compared to the male undergraduates in all the four factors of ESL speaking anxiety. Among the four factors of speaking anxiety, only the factor of „comfort in using English‟ in the classrooms showed a statistically significant difference between male and female undergraduates. Findings of this study would be significant as knowing the level of anxiety among the undergraduates in ESL classrooms will provide the basis for educators to plan better strategies or techniques to help students in overcoming their English speaking anxiety and to improve their oral English proficiency. It will also help students to be aware of their own speaking anxiety level so that they can seek for measures to overcome their speaking anxiety

Resposta androgênica de genótipos brasileiros de trigo a diferentes pré-tratamentos das espigas e a um agente gelificante

The objective of this work was to analyze the androgenic response of Brazilian wheat genotypes to different pretreatments of the spikes, prior to the culture of isolated microspores, and to the effect of a gelling agent in the induction culture medium. Five genotypes were evaluated for embryo formation, green plantregeneration, and spontaneous chromosome duplication. Wheat spikes were subjected to two pretreatments:cold, at 4°C for 21 days; and 2-hydroxynicotinic acid, at 32°C for two days. Culture media were evaluated with or without Ficoll as a gelling agent. Cold produced more embryos and green plants than the chemical pretreatment in four out of five genotypes. Only two genotypes treated with 2-hydroxynicotinic acid were able to produce plants, and one of them produced a single albino plant. Medium containing Ficoll produced moreembryos than liquid medium and promoted a higher number of plants. Spontaneous chromosome duplication varies between genotypes and pretreatments, and shows high variability.O objetivo deste trabalho foi analisar a resposta androgênica de genótipos brasileiros de trigo a diferentes pré-tratamentos das espigas, antes da cultura de micrósporos isolados, e ao efeito de um agente gelificante no meio de cultura de indução. Cinco genótipos foram avaliados quanto à formação de embriões, regeneração de plantas verdes e à duplicação espontânea dos cromossomos. Espigas de trigo foram submetidas a dois pré-tratamentos: frio, a 4°C por 21 dias; e ácido 2-hidroxinicotínico, a 32°C por dois dias. Os meios decultura foram avaliados com ou sem Ficoll como agente gelificante. O frio produziu mais embriões e plantas verdes do que o pré-tratamento químico, em quatro dos cinco genótipos testados. Apenas dois genótipos tratados com ácido 2-hidroxinicotínico foram capazes de produzir plantas, e um deles produziu uma única planta albina. O meio com Ficoll produziu mais embriões do que o meio líquido e gerou maior número de plantas. A duplicação espontânea dos cromossomos varia entre os genótipos e os pré-tratamentos e apresentaalta variabilidade

The protection of Victoria Harbour in Hong Kong : an analysis of civic engagement strategies

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Suicide and socioeconomic determinants in Canada: beyond morality and philosophy

This paper provides new and exciting insight of suicide between genders in Canada for 39 years from a socio-economic perspective. A theoretical framework based on sound economic theory of suicide using Vector Autoregression (VAR) model to establish meaningful relationships between variables incorporated. Additional causality test and beyond sample analysis (forecasting) will be helpful inbeautifying the linkages among the variables employed in this study. It is suggested that both female and male suicidal behaviour can be explained by socio-economic indicators. The findings provide useful insights for policy makers and suicide related agencies to perform a novel approach in dealing with suicides in addition to traditional behavioural correction and counselling strategies in hand. This study should also be helpful in understanding suicide from a broad perspective and analysing suicide in a new economic framework of rational choice theory

El Paisaje como recurso turístico: caso de estudio: Catarina

Tesis (Licenciatura en Turismo y Administración Hotelera)--Universidad Americana, Managua, 2000Este proyecto determina y demuestra el potencial paisajistico como recurso turistico que deriven en propuestas de gestion y promocion

The ATR Inhibitor AZD6738 Synergizes with Gemcitabine In Vitro and In Vivo to Induce Pancreatic Ductal Adenocarcinoma Regression.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers, and overall survival rates have barely improved over the past five decades. The antimetabolite gemcitabine remains part of the standard of care but shows very limited antitumor efficacy. Ataxia telangiectasia and Rad3-related protein (ATR), the apical kinase of the intra-S-phase DNA damage response, plays a central role in safeguarding cells from replication stress and can therefore limit the efficacy of antimetabolite drug therapies. We investigated the ability of the ATR inhibitor, AZD6738, to prevent the gemcitabine-induced intra-S-phase checkpoint activation and evaluated the antitumor potential of this combination in vitro and in vivo In PDAC cell lines, AZD6738 inhibited gemcitabine-induced Chk1 activation, prevented cell-cycle arrest, and restrained RRM2 accumulation, leading to the strong induction of replication stress markers only with the combination. Moreover, synergistic growth inhibition was identified in a panel of 5 mouse and 7 human PDAC cell lines using both Bliss Independence and Loewe models. In clonogenic assays, the combination abrogated survival at concentrations for which single agents had minor effects. In vivo, AZD6738 in combination with gemcitabine was well tolerated and induced tumor regression in a subcutaneous allograft model of a KrasG12D; Trp53R172H; Pdx-Cre (KPC) mouse cancer cell line, significantly extending survival. Remarkably, the combination also induced regression of a subgroup of KPC autochthonous tumors, which generally do not respond well to conventional chemotherapy. Altogether, our data suggest that AZD6738 in combination with gemcitabine merits evaluation in a clinical trial in patients with PDAC. Mol Cancer Ther; 17(8); 1670-82. ©2018 AACR

Quantifying cell cycle-dependent drug sensitivities in cancer using a high throughput synchronisation and screening approach.

BACKGROUND: Chemotherapy and targeted agent anti-cancer efficacy is largely dependent on the proliferative state of tumours, as exemplified by agents that target DNA synthesis/replication or mitosis. As a result, cell cycle specificities of a number of cancer drugs are well known. However, they are yet to be described in a quantifiable manner. METHODS: A scalable cell synchronisation protocol used to screen a library of 235 anti-cancer compounds exposed over six hours in G1 or S/G2 accumulated AsPC-1 cells to generate a cell cycle specificity (CCS) score. FINDINGS: The synchronisation method was associated with reduced method-related cytotoxicity compared to nocodazole, delivering sufficient cell cycle purity and cell numbers to run high-throughput drug library screens. Compounds were identified with G1 and S/G2-associated specificities that, overall, functionally matched with a compound's target/mechanism of action. This annotation was used to describe a synergistic schedule using the CDK4/6 inhibitor, palbociclib, prior to gemcitabine/AZD6738 as well as describe the correlation between the CCS score and published synergistic/antagonistic drug schedules. INTERPRETATION: This is the first highly quantitative description of cell cycle-dependent drug sensitivities that utilised a tractable and tolerated method with potential uses outside the present study. Drug treatments such as those shown to be G1 or S/G2 associated may benefit from scheduling considerations such as after CDK4/6 inhibitors and being first in drug sequences respectively. FUNDING: Cancer Research UK (CRUK) Institute core grants C14303/A17197 and C9545/A29580. The Li Ka Shing Centre where this work was performed was generously funded by CK Hutchison Holdings Limited, the University of Cambridge, CRUK, The Atlantic Philanthropies and others

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

The effect of integrated cardiac rehabilitation versus treatment as usual for atrial fibrillation patients treated with ablation:the randomised CopenHeartRFA trial protocol

INTRODUCTION: Atrial fibrillation affects almost 2% of the population in the Western world. To preserve sinus rhythm, ablation is undertaken in symptomatic patients. Observational studies show that patients with atrial fibrillation often report a low quality of life and are less prone to be physically active due to fear of triggering fibrillation. Small trials indicate that exercise training has a positive effect on exercise capacity and mental health, and both patients with recurrent atrial fibrillation and in sinus rhythm may benefit from rehabilitation in managing life after ablation. No randomised trials have been published on cardiac rehabilitation for atrial fibrillation patients treated with ablation that includes exercise and psychoeducational components. AIM: To test the effects of an integrated cardiac rehabilitation programme versus treatment as usual for patients with atrial fibrillation treated with ablation. METHODS AND ANALYSIS DESIGN: The trial is a multicentre parallel arm design with 1:1 randomisation to the intervention and control group with blinded outcome assessment. 210 patients treated for atrial fibrillation with radiofrequency ablation will be included. The intervention consists of a rehabilitation programme including four psychoeducative consultations with a specially trained nurse and 12 weeks of individualised exercise training, plus the standard medical follow-up. Patients in the control group will receive the standard medical follow-up. The primary outcome measure is exercise capacity measured by the VO(2) peak. The secondary outcome measure is self-rated mental health measured by the Short Form 36 questionnaire. Postintervention, qualitative interviews will be conducted in 10% of the intervention group. ETHICS AND DISSEMINATION: The protocol is approved by the regional research ethics committee (number H-1-2011-135), the Danish Data Protection Agency (reg. nr. 2007-58-0015) and follows the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and may possibly impact on rehabilitation guidelines. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01523145