1,721,097 research outputs found

    Screening test accuracy of portable devices that can be used to perform colposcopy for detecting CIN2+ in low- and middle-income countries: a systematic review and meta-analysis.

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    BACKGROUND Portable devices that can be used to perform colposcopy may improve cervical cancer screening in low- and middle-income countries (LMIC) where access to colposcopy is limited. The objective of this study was to systematically review the diagnostic test accuracy (DTA) of these devices for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). METHODS In accordance with our protocol (Prospero CRD42018104286), we searched Embase, Medline and the Cochrane Controlled Register of Trials up to 9/2019. We included DTA studies, which investigated portable devices with moderate-to-high optical magnification (≥ 6×) for colposcopy, as described in the manual for Colposcopy and Treatment by the International Agency for Research on Cancer, with a histopathological reference standard. We used the QUADAS-2 tool to assess study quality. We examined results for sensitivity and specificity in paired forest plots, stratified by stages in the clinical pathway. We pooled estimates of test accuracy for the index test, used as an add-on to other tests, using a bivariate random-effect model. RESULTS We screened 1737 references and assessed 239 full-text articles for eligibility. Five single-gate DTA studies, including 2693 women, met the inclusion criteria. Studies evaluated two devices (Gynocular™ and Pocket) at different stages of the screening pathway. In three studies, which used the index test in an add-on capacity in 1273 women, we found a pooled sensitivity of 0.79 (95% CI 0.55-0.92) and specificity of 0.83 (95% CI 0.59-0.94). The main sources of bias were partial verification, incorporation and classification bias. CONCLUSION Few studies have evaluated portable devices able to perform colposcopy, so their accuracy for the detection of CIN2+ remains uncertain. Future studies should include patient-relevant and long-term outcomes, including missed cases, overtreatment, residual and recurrent disease. To meet the challenge of eliminating cervical cancer in LMIC, methods for visual assessment of the cervix need urgent redress

    Molecular Cloning, Heterologous Expression, and Steady-State Kinetics of Campylobacter Jejuni Periplasmic Nitrate Reductase

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    Mononuclear molybdenum enzymes catalyze a variety of reactions that are essential in the cycling of nitrogen, carbon, arsenic, and sulfur. For decades, the structure and function of these crucial enzymes have been investigated to develop a fundamental knowledge for this vast family of enzymes and the chemistries they catalyze. The dimethyl sulfoxide reductase (DMSOR) family is the most diverse family of molybdoenzymes and, the members of this family catalyze a myriad of reactions that are important in microbial life processes. Periplasmic nitrate reductase (Nap) is an important member of the DMSO reductase family that catalyzes the reduction of nitrate (NO3 - ) to nitrite (NO2 - ), and yet the physiological role of Nap is not completely clear. Enzymes in this family can transform multiple substrates; however, quantitative information about the substrate preference is sparse and more importantly, the reasons for the substrate selectivity are not clear. Substrate specificity is proposed to be tuned by the ligands coordinating the molybdenum atom in the active site. As such, periplasmic nitrate reductase is utilized as a vehicle to understand the substrate preference and delineate the mechanistic underpinning of these differences. To this end, NapA from Campylobacter jejuni has been heterologously overexpressed, and a series of variants, where the molybdenum-coordinating cysteine has been replaced with another amino acid, has been produced. The kinetic and biochemical properties of these variants will be discussed and compared with those of the native enzyme, providing quantitative information to understand the function

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Secondary prevention of cervical cancer in low- and middle-income countries.

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    With early and effective treatment of precancerous cervical lesions, cervical cancer can be prevented. Many countries that have implemented cervical cancer screening have observed a substantial reduction in cervical cancer-related morbidity and mortality over the last decades. However, vast geographic and socioeconomic disparities exist today, with most cervical cancers and deaths occurring in low- and middle-income countries (LMIC). Especially in countries with a high prevalence of human immunodeficiency virus (HIV), cervical cancer remains the leading cause of cancer-related death among women. In May 2018, the World Health Organization (WHO) called for the elimination of cervical cancer (defined as an incidence rate of 4 per 100 000 women-years) and identified human papillomavirus (HPV) vaccination, screening, and treatment targets to achieve this. Mathematical modeling studies have shown that cervical cancer can be eliminated by highly resourced, well-organized screening programs, and HPV vaccination. A major scale-up of the screening programs is required to reach the WHO targets in LMIC. However, screening strategies that have successfully reduced the incidence of cervical cancer in some high-income countries cannot be replicated in LMIC and, as such, context-specific strategies are essential. In my thesis, I used different study designs to increase understanding on the secondary prevention of cervical cancer in LMIC and women living with HIV (WLHIV). Observational cohort studies Specifically, studies 1 and 2 (Chapter 3.1 and 3.2, respectively) are cohort studies evaluating routinely collected data from visual inspection after application of acetic acid (VIA)-based screening programs in Zambia and Zimbabwe, respectively. Study 1 (Chapter 3.1) summarized cervical screening data from all 11 government health facilities in Lusaka, Zambia that provided cervical cancer screening services between January 2010 and July 2019. We assessed screening frequency, examined predictors of positive screening results, and described patterns of sensitization strategies according to age group and HIV status. Study 2 (Chapter 3.2) summarized data gathered from an antiretroviral clinic (ART) clinic with on-site cervical cancer screening capacity. We included 1624 women who had their first ART clinic appointment between 2012 and 2017 and also included the one-year follow-up appointment, taking the follow-up period to 2018. In this cohort study we present essential screening stages in terms of a secondary cervical cancer prevention cascade with two arms: screening and preventative treatment. In doing so, we have explored how women in ART clinics transitioned through linked stages of cervical cancer screening. We found that in both study populations, screening frequency increased over time. In study 1 (Chapter 3.1) screening frequency increased 65.7% from 2010 to 2019. Furthermore, in study 2 (Chapter 3.2) we found that women who enrolled into care between 2015 and 2018 were more likely to complete the cervical cancer screening cascade than women who enrolled between 2012 and 2015 (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.16–1.49). The cascade analysis identified two important gaps in the screening continuum. First, only 79.5% (95% CI 75.1–83.2) of women who had a positive screening result received treatment within 2 years. This falls short of the WHO target of 90% for treatment of precancerous cervical lesions. We also found a low number of women who were screen-negative after treatment of precancerous cervical lesions (36.1%, 95% CI 31.2–40.7) which raises concerns about the effectiveness of treatment and the accuracy of screening tests used to detect precancerous cervical lesions among WLHIV. Evidence synthesis studies Studies 3 and 4 (Chapter 3.3 and 3.4, respectively) synthesize evidence for the management of precancerous cervical lesions and devices that may be used for colposcopy in low- and middle-income countries. Although visual assessment of the cervix remains essential for screening and treatment of precancerous cervical lesions, colposcopy is often not available in low- and middle-income countries (LMIC, Chapter 3.3). Study 4 (Chapter 3.4) is a systematic review of the diagnostic test accuracy of portable devices able to perform colposcopy. We found that when these devices are used as add-on screening tests, a pooled sensitivity of 0.79 (95% CI 0.54–0.92) and specificity of 0.83 (95% CI 0.59–0.94) is achieved. The wide confidence intervals of these estimates indicate that the accuracy of portable devices able to perform colposcopy for the detection of CIN 2+ remains uncertain. Clinical test accuracy studies Studies 5 and 6 (Chapter 3.5 and 3.6, respectively) refer to clinical investigations of the diagnostic test accuracy of the Gynocular™, a portable device that can be used for colposcopy. Study 5 (Chapter 3.5) is our protocol which outlines the aims and methods of the first study to evaluate the Gynocular™ in a population of WLHIV exclusively. In this study we are also evaluating other relevant point-of-care tests; the high-risk human papillomavirus test (HR-HPV, GeneXpert™, Cepheid, USA) and VIA. We plan to measure the sensitivity and specificity of each test in a stand-alone capacity as well as the combination of tests. Extensions to this study include a cost analysis, the development of an automated visual assessment tool using pattern recognition, as well as exploring associations with trichomoniasis (a common STI in this setting. Study 6 (Chapter 3.6) is a cross-sectional pilot study evaluating the telemedicine capacity of the device. Here we assessed the diagnostic accuracy of the Gynocular™ used during live colposcopy versus static-image assessments using Swede score evaluation for detecting CIN 2+ lesions. We evaluated 495 images from 94 VIA-positive women. Thirteen (13.9%) had CIN 2+ on biopsy. We found that live and static image assessors had similar accuracy for detecting CIN 2+ lesions (area under curve = 0.69 versus 0.71, p = 0.63) and the Swede score could be used to optimize sensitivity or specificity. In conclusion, the studies presented in this thesis contribute to a sparse knowledge base on secondary prevention of cervical cancer in WLHIV. The studies suggest that cervical cancer screening and treatment quality needs to be improved for WLHIV in LMIC and that reforms must be context-specific, taking into account the population characteristics and the healthcare infrastructure concerned. These gaps need to be addressed before the WHO initiative to eliminate cervical cancer at the global level can be successful

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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