215 research outputs found

    Play-Based Learning: Benefits and Challenges of its Implementation

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    This study explores how Eritrean pre-school educators viewed and conceptualized play-based learning (PBL), the benefits, and challenges of its implementation. A semi-structured interview was conducted with nine teachers, six principals, and two pre-primary education curriculum developers. Interviews were thematically analyzed. The study found discrepancies between participants’ views and their implementation. Our findings indicate that most of the participants viewed PBL as incorporating both free-play and guided play. However, the result of this study revealed that free play cannot effectively be used as an instrument to teach lessons that have specific academic objectives such as numeracy and literacy skills. Besides, the researchers sought to investigate the actual practices of PBL and the study found that majority of educators were placed at the Child Adult Involvement Continuum extremes, free-play, and direct instruction. Furthermore, the result revealed that various challenges were teachers face as they try to implement PBL, but the most common barrier discussed by interviewees was the lack of awareness of parents and principals towards PBL. Finally, the study concluded that the reason teachers lie at the two extremes of the Child Adults Involvement Continuum could be due to their views towards PBL, and its benefits and the challenges they face in implementing it

    Outcomes of a clinical diagnostic algorithm for management of ambulatory smear and Xpert MTB/Rif negative HIV infected patients with presumptive pulmonary TB in Uganda: a prospective study

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    Introduction: Diagnostic guidelines for Tuberculosis (TB) in HIV infected patients previously relied on microscopy where the value of initial antibiotic treatment for exclusion of pulmonary TB (PTB) was limited. New guidelines rely on the Xpert MTB Rif test (Xpert). However, the value of the antibiotic treatment remains unclear particularly in individuals who are smear-negative and Xpert-negative-given Xpert has only moderate sensitivity for smear-negative PTB. We assessed an algorithm involving initial treatment with antibiotics prior empiric TB treatment in HIV patients with presumptive PTB who were both smear and Xpert negative. Methods: We performed a prospective study with six month follow-up to establish patient response to a course of broad spectrum antibiotics prior empiric TB treatment between March 2012 and June 2013. We calculated the proportion of patients who responded to the antibiotic treatment and those who did not. We computed the crude and adjusted odds ratios with their 95% confidence intervals, for response to the antibiotic treatment on various patient characteristics. We report treatment outcomes for patients who received broad spectrum antibiotics only or who were initiated empiric TB treatment. Results: Our cohort comprised 162 smearnegative and Xpert-negative patients, of whom 59% (96 of 162) were female, 81% (131 of 162) were on antiretroviral therapy (ART) for a median of 8.7 months. Overall, 88% (141 of 160) responded to the antibiotic treatment, 8% (12 of 160) got empiric TB treatment and 4% (7 out of 160) were treated for other respiratory disease. The odds of improvement on antibiotics were lower in patients with advanced HIV disease than in patients with early HIV disease. Adjusted odds ratios were significant for HIV clinical stage (AOR; 0.038,) and duration on ART (AOR; 1.038,). Conclusion: The majority of HIV patients with presumptive PTB with smear-negative and Xpert negative results improved on the antibiotic treatment and did not require empiric TB treatment. Initial antibiotic treatment appeared more successful in patients with less advanced HIV disease. Findings from our study suggest it is useful to initiate HIV infected patients with presumptive PTB having smear and Xpert negative results on an initial course of antibiotic treatment prior empiric TB treatment.Pan African Medical Journal 2016; 2

    Targeting androgen receptor activation function-1 with EPI to overcome resistance mechanisms in castration-resistant prostate cancer

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    Acknowledgments The authors thank Kate Watt (University of Aberdeen, Aberdeen, Scotland) for technical support. The authors are also grateful to Country Meadows Senior Men's Golf Charity Classic for financial support of this research. Financial support: This research was supported by grants to MDS from the NCI (2R01CA105304), the Canadian Institutes of Health Research (MOP79308) and the US Army Medical Research and Materiel Command Prostate Cancer Research Program (E81XWH-11-1-0551). Research by IJM’s group was supported by the Chief Scientist’s Office of the Scottish Government (ETM-258 and -382). We are grateful to Country Meadows Senior Men’s Golf Charity Classic for financial support of this research.Peer reviewedPostprin

    Energy spread of ultracold electron bunches extracted from a laser cooled gas

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    Ultrashort and ultracold electron bunches created by near-threshold femtosecond photoionization of a laser-cooled gas hold great promise for single-shot ultrafast diffraction experiments. In previous publications the transverse beam quality and the bunch length have been determined. Here the longitudinal energy spread of the generated bunches is measured for the first time, using a specially developed Wien filter. The Wien filter has been calibrated by determining the average deflection of the electron bunch as a function of magnetic field. The measured relative energy spread σUU=0.64±0.09%\frac{\sigma_{U}}{U} = 0.64 \pm 0.09\% agrees well with the theoretical model which states that it is governed by the width of the ionization laser and the acceleration length

    Seasonal surface drainage of sloping farmland : a review of its hydrogeomorphic impacts

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    The combination of runoff-generating areas (saturated soils) and overland flow concentration in features such as drainage ditches makes sloping farmland vulnerable to soil erosion. The establishment of drainage ditches aims at draining the excess of water from the farmland, particularly in areas where soils are saturated in the rainy season. The hydrogeomorphic impacts on the farmland itself and on downstream areas need however also to be studied. Off site, downstream problems comprise higher peak discharges, leading to gully initiation, an increase in sediment load, and flooding problems. On-site problems such as the development of the drainage ditches into (ephemeral) gullies are less documented, although they may be important, as illustrated in the Lake Tana Basin (Ethiopia). The similarities and interactions between ephemeral gully channels and drainage ditches have to be considered to better understand all effects of drainage. Drainage ditches are a potential source of conflict between farmers with different interests and power, as well as between upstream and downstream users. A case study on drainage ditches on sloping farmlands in the Lake Tana Basin showed that nine out of ten catchments had drainage densities by ditches ranging from 53 to 510 m ha−1. Drainage ditches were constructed with an average top width of 27 (±9) cm. A significant correlation was found between stone bund density (physical conservation structures) and ditch drainage density (R = −0·72), in line with the Ethiopian government's ban on drainage ditches in farmlands where stone bunds have been constructed

    A signal from inside the peroxisome initiates its division by promoting the remodeling of the peroxisomal membrane

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    We define the dynamics of spatial and temporal reorganization of the team of proteins and lipids serving peroxisome division. The peroxisome becomes competent for division only after it acquires the complete set of matrix proteins involved in lipid metabolism. Overloading the peroxisome with matrix proteins promotes the relocation of acyl-CoA oxidase (Aox), an enzyme of fatty acid β-oxidation, from the matrix to the membrane. The binding of Aox to Pex16p, a membrane-associated peroxin required for peroxisome biogenesis, initiates the biosynthesis of phosphatidic acid and diacylglycerol (DAG) in the membrane. The formation of these two lipids and the subsequent transbilayer movement of DAG initiate the assembly of a complex between the peroxins Pex10p and Pex19p, the dynamin-like GTPase Vps1p, and several actin cytoskeletal proteins on the peroxisomal surface. This protein team promotes membrane fission, thereby executing the terminal step of peroxisome division

    Game theory of mind

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    This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

    Regression of Castrate-Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor

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    SummaryCastration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity

    FUS/TLS Is a Co-Activator of Androgen Receptor in Prostate Cancer Cells

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    Androgen receptor (AR) is a member of the nuclear receptor family of transcription factors. Upon binding to androgens, AR becomes transcriptionally active to regulate the expression of target genes that harbor androgen response elements (AREs) in their promoters and/or enhancers. AR is essential for the growth and survival of prostate cancer cells and is therefore a target for current and next-generation therapeutic modalities against prostate cancer. Pathophysiologically relevant protein-protein interaction networks involving AR are, however, poorly understood. In this study, we identified the protein FUsed/Translocated in LipoSarcoma (FUS/TLS) as an AR-interacting protein by co-immunoprecipitation of endogenous proteins in LNCaP human prostate cancer cells. The hormonal response of FUS expression in LNCaP cells was shown to resemble that of other AR co-activators. FUS displayed a strong intrinsic transactivation capacity in prostate cancer cells when tethered to basal promoters using the GAL4 system. Chromatin immunoprecipitation experiments showed that FUS was recruited to ARE III of the enhancer region of the PSA gene. Data from ectopic overexpression and “knock-down” approaches demonstrated that AR transcriptional activity was enhanced by FUS. Depletion of FUS reduced androgen-dependent proliferation of LNCaP cells. Thus, FUS is a novel co-activator of AR in prostate cancer cells
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