371 research outputs found

    An Investigation into Libyan EFL Novice Secondary School Teachers' Current Knowledge and Practice of Speaking Assessment: A Socio-cultural Perspective

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    This study sought to further understanding of EFL teachers’ knowledge of speaking assessment and how their knowledge informs their speaking assessment practices in classrooms. Based on a socio-cultural perspective, the present study aimed at investigating EFL novice teachers’ current knowledge and practice of speaking assessment in a Libyan secondary school context. The study is based on the interpretive paradigm and adopted social constructionism as a philosophical stance. Quantitative and qualitative methods of data collection were employed in two sequential phases. The findings of this study indicated that EFL novice teachers’ current knowledge of speaking assessment is complex and that was reflected in the different ways these teachers interpreted the concept of speaking assessment and in the ways they expressed their beliefs and values regarding how speaking assessment needs to be or is implemented in the classroom settings. Three main issues regarding teachers’ knowledge of speaking assessment emerged from the data. The first issue is that these teachers, although showing some variability in their knowledge and practice, seem to base their assessment practice on a view of spoken language being more about linguistic content than communicative effect. Secondly, that they mostly seem to afford more importance to summative assessment than to formative assessment. Thirdly, they have a view of assessment that focuses on the content to be assessed rather than on the process of assessment. The findings also indicated that while teachers refer to contextual factors that influence how they implement their knowledge into practice, their understanding of the notion of assessment seems to have more influence on their implementation of speaking assessment as process than that of the context. That is, their current understandings of the notion of spoken language seem to contribute to their current practice of speaking assessment. Also of significance are the participants’ views of the role of context. The results showed that although contexts are similar in some aspects, especially those related to institutional factors, teachers’ views show the uniqueness of the context, especially in the light of the unanticipated social, political and institutional changes. The implications of this study suggest that these EFL novice teachers’ current knowledge of language and of assessment goes beyond factual knowledge to their perceptions of language and their understandings of the purpose of assessment. They also suggest that context plays a role on their current knowledge and practice of speaking assessment. Thus, this study provides further understanding that what these teachers know and how they use their knowledge in practice arises from a complex interweaving of context and individual understandings.Libyan Higher Ministry of Educatio

    Finding the association of mRNA and miRNA using Next Generation Sequencing data of Kidney renal cell carcinoma

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    MicroRNAs (miRNAs) are a class of 22-nucleotide endogenous noncod- ing RNAs, plays important role in regulating target gene expression via repress- ing translation or promoting messenger RNAs (mRNA) degradation. Numerous re- searchers have found that miRNAs have serious effects on cancer. Therefore, study of mRNAs and miRNAs together through the integrated analysis of mRNA and miRNA expression profiling could help us in getting a deeper insight into the can- cer research. In this regards, High-Throughput Sequencing data of Kidney renal cell carcinoma is used here. The proposed method focuses on identifying mRNA- miRNA pair that has a signature in kidney tumor sample. For this analysis, Ran- dom Forests, Particle Swarm Optimization and Support Vector Machine classifier is used to have best sets of mRNAs-miRNA pairs. Additionally, the significance of selected mRNA-miRNA pairs is tested using gene ontology and pathway analysis tools. Moreover, the selected mRNA-miRNA pairs are searched based on changes in expression values of the used mRNA and miRNA dataset

    Profiling the Effects of Systemic Antibiotics for Acne, Including the Narrow-Spectrum Antibiotic Sarecycline, on the Human Gut Microbiota

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    Treatment for moderate-to-severe acne vulgaris relies on prolonged use of oral tetracycline-class antibiotics; however, these broad-spectrum antibiotics are often associated with off-target effects and negative gastrointestinal sequelae. Sarecycline is a narrow-spectrum antibiotic treatment option. Here, we investigated the effect of prolonged sarecycline exposure, compared with broad-spectrum tetracyclines (doxycycline and minocycline) upon the colonic microbiota. Three in vitro models of the human colon were instilled with either minocycline, doxycycline or sarecycline, and we measured microbiota abundance and diversity changes during and after antibiotic exposure. Significant reductions in microbial diversity were observed following minocycline and doxycycline exposure, which failed to recover post antibiotic withdrawal. Specifically, minocycline caused a ~10% decline in Lactobacillaceae and Bifidobacteriaceae abundances, while doxycycline caused a ~7% decline in Lactobacillaceae and Bacteroidaceae abundances. Both minocycline and doxycycline were associated with a large expansion (>10%) of Enterobacteriaceae. Sarecycline caused a slight decline in bacterial diversity at the start of treatment, but abundances of most families remained stable during treatment. Ruminococcaceae and Desulfovibrionaceae decreased 9% and 4%, respectively, and a transient increased in Enterobacteriaceae abundance was observed during sarecycline administration. All populations recovered to pre-antibiotic levels after sarecycline exposure. Overall, sarecycline had minimal and transient impact on the gut microbiota composition and diversity, when compared to minocycline and doxycycline

    The Burden of Skin and Subcutaneous Diseases in the United States From 1990 to 2017

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    IMPORTANCE Skin and subcutaneous diseases affect the health of millions of individuals in the US. Data are needed that highlight the geographic trends and variations of skin disease burden across the country to guide health care decision-making. OBJECTIVE To characterize trends and variations in the burden of skin and subcutaneous tissue diseases across the US from 1990 to 2017. DESIGN, SETTING, AND PARTICIPANTS For this cohort study, data were obtained from the Global Burden of Disease (GBD), a study with an online database that incorporates current and previous epidemiological studies of disease burden, and from GBD 2017, which includes more than 90 000 data sources such as systematic reviews, surveys, population-based disease registries, hospital inpatient and outpatient data, cohort studies, and autopsy data. The GBD separated skin conditions into 15 subcategories according to incidence, prevalence, adequacy of data, and standardized disease definitions. GBD 2017 also estimated the burden from melanoma of the skin and keratinocyte carcinoma. Data analysis for the present study was conducted from September 9, 2019, to March 31, 2020. MAIN OUTCOMES AND MEASURES Primary study outcomes included age-standardized disability-adjusted life-years (DALYs), incidence, and prevalence. The data were stratified by US states with the highest and lowest age-standardized DALY rate per 100 000 people, incidence, and prevalence of each skin condition. The percentage change in DALY rates in each state was calculated from 1990 to 2017. RESULTS Overall, age-standardized DALY rates for skin and subcutaneous diseases increased from 1990 (821.6; 95% uncertainty interval [UI], 570.3-1124.9) to 2017 (884.2; 95% UI, 614.0-1207.9) in all 50 states and the District of Columbia. The degree of increase varied according to geographic location, with the largest percentage change of 0.12% (95% UI, 0.09%-0.15%) in New York and the smallest percentage change of 0.04% (95% UI, 0.02%-0.07%) in Colorado, 0.04% (95% UI, 0.01%-0.06%) in Nevada, 0.04% (95% UI, 0.02%-0.07%) in New Mexico, and 0.04% (95% UI, 0.02%-0.07%) in Utah. The age-standardized DALY rate, incidence, and prevalence of specific skin conditions differed among the states. New York had the highest age-standardized DALY rate for skin and subcutaneous disease in 2017 (1097.0 [95% UI, 764.9-1496.1]), whereas Wyoming had the lowest age-standardized DALY rate (672.9 [95% UI, 465.6-922.3]). In all 50 states and the District of Columbia, women had higher age-standardized DALY rates for overall skin and subcutaneous diseases than men (women: 971.20 [95% UI, 676.76-1334.59] vs men: 799.23 [95% UI, 559.62-1091.50]). However, men had higher DALY rates than women for malignant melanoma (men: 80.82 [95% UI, 51.68-123.18] vs women: 42.74 [95% UI, 34.05-70.66]) and keratinocyte carcinomas (men: 37.56 [95% UI, 29.35-49.52] vs women: 14.42 [95% UI, 10.01-20.66]). CONCLUSIONS AND RELEVANCE Data from the GBD suggest that the burden of skin and subcutaneous disease was large and that DALY rate trends varied across the US; the age-standardized DALY rate for keratinocyte carcinoma appeared greater in men. These findings can be used by states to target interventions and meet the needs of their population

    Canadian Burden of Skin Disease From 1990 to 2017: Results From the Global Burden of Disease 2017 Study

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    Background: Skin diseases can have high morbidity that can be costly to society and individuals. To date, there has been no comprehensive assessment of the burden of skin disease in Canada. Objectives: To evaluate the burden of 18 skin and subcutaneous diseases from 1990 to 2017 in Canada using the Global Burden of Disease (GBD) data. Methods: The 2017 GBD study measures health loss from 359 diseases and injuries in 195 countries; we evaluated trends in population health in Canada from 1990 to 2017 using incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs). Data are presented as rates (per 100 000), counts, or percent change with the uncertainty interval in brackets. Results: From 1990 to 2017 for all skin diseases, DALY rates increased by 8 to 971 per 100 000 (674-1319), YLD rates increased by 8 to 897 per 100 000 (616-1235), YLL rates increased by 4 to 74 per 100 000 (53-89), and death rates increased by 18 to 5 per 100 000 (3-6). DALY rates for melanoma increased by 2 to 54 per 100 000 (39-68), for keratinocyte carcinoma by 14 to 17 per 100 000 (16-19), and for skin and subcutaneous disease by 8 to 900 per 100 000 (619-1233). The observed over expected ratios were higher for skin and subcutaneous disease (1.37) and keratinocyte carcinoma (1.17) and were lower for melanoma (0.73). Conclusions: The burden of skin disease has increased in Canada since 1990. These results can be used to guide health policy regarding skin disease in Canada. © The Author(s) 2020

    CAR-T cell. the long and winding road to solid tumors

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    Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

    A bispecific chimeric antigen receptor molecule enhances T cell activation through dual immunological synapse formation and offsets antigen escape in glioblastoma

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    Background Antigen escape tumor cell variants prevail in tumors recurring after treatment with chimeric antigen receptor (CAR) T cells with a single specificity. Recurrent tumors preserve alternative non-targeted tumor associated antigens. Hypothesis A bispecific CAR will mitigate antigen escape enhancing the antitumor activity of T cells. Methods and results HER2 and IL13Rα2 are currently targeted in Phase I glioblastoma (GBM) trials using CAR T cells. We created a bispecific CAR molecule with a HER2-specific scFv joined in tandem to an IL13Rα2-binding moiety in the CAR exodomain (Tandem CAR) and a CD28.ζ signaling endodomain. We used computational modeling to interrogate this design. GBM patients' Tandem CAR T cells showed distinct binding to soluble HER2 and IL13Rα2 and killed primary autologous GBM cells. Three-dimensional reconstitution and quantification of confocal images of the Tandem CAR T cell/tumor interface revealed enhanced bifunctional immunological synapses compared to conventional CARs. Further, Tandem CAR T cells exhibited significantly enhanced inexhaustible activation dynamics when compared to conventional HER2 or IL13Rα2 CAR T cells and better controlled established GBM in an orthotopic murine model by offsetting both HER2 and IL13Rα2 escape. Conclusion Tandem chimeric antigen receptors enhance T cell activation and mitigate antigen escape through bifunctional immunological synapse formation in GBM

    Pre-Conception Interventions for Subfertile Couples Undergoing Assisted Reproductive Technology Treatment: Modeling Analysis

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    BACKGROUND: Approximately 1 in 7 couples experience subfertility, many of whom have lifestyles that negatively affect fertility, such as poor nutrition, low physical activity, obesity, smoking, or alcohol consumption. Reducing lifestyle risk factors prior to pregnancy or assisted reproductive technology treatment contributes to the improvement of reproductive health, but cost-implications are unknown. OBJECTIVE: The goal of this study was to evaluate reproductive, maternal pregnancy, and birth outcomes, as well as the costs of pre-conception lifestyle intervention programs in subfertile couples and obese women undergoing assisted reproductive technology. METHODS: Using a hypothetical model based on quantitative parameters from published literature and expert opinion, we evaluated the following lifestyle intervention programs: (1) Smarter Pregnancy, an online tool; (2) LIFEstyle, which provides outpatient support for obese women; (3) concurrent use of both Smarter Pregnancy and LIFEstyle for obese women; (4) smoking cessation in men; and (5) a mindfulness mental health support program using group therapy sessions. The model population was based on data from the Netherlands. RESULTS: All model-based analyses of the lifestyle interventions showed a reduction in the number of in vitro fertilization, intracytoplasmic sperm injection, or intrauterine insemination treatments required to achieve pregnancy and successful birth for couples in the Netherlands. Smarter Pregnancy was modeled to have the largest increase in spontaneous pregnancy rate (13.0%) and the largest absolute reduction in potential assisted reproductive technology treatments. Among obese subfertile women, LIFEstyle was modeled to show a reduction in the occurrence of gestational diabetes, maternal hypertensive pregnancy complications, and preterm births by 4.4%, 3.8%, and 3.0%, respectively, per couple. Modeled cost savings per couple per year were €41 (US 48.66),360(US48.66), €360 (US 427.23), €513 (US 608.80),586(US608.80), €586 (US 695.43), and €1163 (US $1380.18) for smoking cessation, mindfulness, Smarter Pregnancy, combined Smarter Pregnancy AND LIFEstyle, and LIFEstyle interventions, respectively. CONCLUSIONS: Although we modeled the potential impact on reproductive outcomes and costs of fertility treatment rather than collecting real-world data, our model suggests that of the lifestyle interventions for encouraging healthier behaviors, all are likely to be cost effective and appear to have positive effects on reproductive, maternal pregnancy, and birth outcomes. Further real-world data are required to determine the cost-effectiveness of pre-conception lifestyle interventions, including mobile apps and web-based tools that help improve lifestyle, and their effects on reproductive health. We believe that further implementation of the lifestyle app Smarter Pregnancy designed for subfertile couples seeking assistance to become pregnant is likely to be cost-effective and would allow reproductive health outcomes to be collected

    Facilitated sequence assembly using densely labeled optical DNA barcodes:A combinatorial auction approach

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    <div><p>The output from whole genome sequencing is a set of contigs, i.e. short non-overlapping DNA sequences (sizes 1-100 kilobasepairs). Piecing the contigs together is an especially difficult task for previously unsequenced DNA, and may not be feasible due to factors such as the lack of sufficient coverage or larger repetitive regions which generate gaps in the final sequence. Here we propose a new method for scaffolding such contigs. The proposed method uses densely labeled optical DNA barcodes from competitive binding experiments as scaffolds. On these scaffolds we position theoretical barcodes which are calculated from the contig sequences. This allows us to construct longer DNA sequences from the contig sequences. This proof-of-principle study extends previous studies which use sparsely labeled DNA barcodes for scaffolding purposes. Our method applies a probabilistic approach that allows us to discard “foreign” contigs from mixed samples with contigs from different types of DNA. We satisfy the contig non-overlap constraint by formulating the contig placement challenge as a combinatorial auction problem. Our exact algorithm for solving this problem reduces computational costs compared to previous methods in the combinatorial auction field. We demonstrate the usefulness of the proposed scaffolding method both for synthetic contigs and for contigs obtained using Illumina sequencing for a mixed sample with plasmid and chromosomal DNA.</p></div
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