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Presents a collection of short stories about significant moments which marked a turning point in the lives of young protagonists by such authors as Anne Mazer, Alan Stewart Carl, Dave Eggers, and Peter Bacho.

This paper describes the development of an RStudio (now known as Posit) dashboard derived from the Integrated Postsecondary Educational Data System, the United States Census Bureau, and the Bureau of Labor Statistics and provides the user with institutional, community, and career information of IPEDS reporting higher education institutions in the United States and its territories. With this dashboard, users can select and learn about institutions, explore enrollment trends and demographics, compare outcomes, and correlate community and institutional variables. Users can also link degrees to career projections and wages. This paper explains how the dashboard was developed with examples of R programming language.

Although the human immunodeficiency virus (HIV) infection pandemic has had a catastrophic impact on tuberculosis (TB) control efforts, especially in sub-Saharan Africa, most of the fundamental concepts reflected in the directly observed treatment, short course (DOTS) strategy still hold true in the HIV era. What has changed, and dramatically, is the importance of speedy and accurate TB diagnosis and the difficulty of achieving this. The disproportionate amount of smear-negative disease in sub-Saharan Africa, which shoulders two-thirds of the global burden of HIV infection and acquired immunodeficiency syndrome, has greatly complicated TB case detection and disease control. Now, 15 years after TB rates began to soar in countries where HIV infection is prevalent, we have learned that the conventional approach—passively waiting for patients with advanced symptomatic disease to make their way to microscopy centers for diagnosis—has disastrous consequences. Without better diagnostic tools for TB and effective strategies for their implementation, transmission will not be interrupted, mortality will not be checked, and TB will not be controlled in areas where HIV infection is prevalent. Fortunately, a number of technical opportunities exist for the creation of improved diagnostic tests. Developing and exploiting such tests to support TB control in HIV-infected populations is an urgent priority. A substantial public sector effort is under way to work in partnership with the biotechnology industry to accelerate progress toward that goal. In this article, we will define the need for better TB tests and describe technologies being developed to meet that need.

Samples from patients with suspected TB were assayed for TB and drug resistance with several different techniques. An automated molecular test showed a sensitivity of 98% in smear-positive, culture-positive samples and a sensitivity of 72–90% in smear-negative, culture-positive samples, and it identified rifampin resistance >97% of the time. Only a small fraction of the estimated 500,000 patients who have multidrug-resistant tuberculosis and 1.37 million patients who have coinfection with tuberculosis and the human immunodeficiency virus (HIV) worldwide each year have access to sufficiently sensitive case detection or drug-susceptibility testing. 1 Diagnostic delay, aggravated by the disproportionate frequency of smear-negative disease in HIV-associated tuberculosis, is common. 2 – 5 The failure to quickly recognize and treat affected patients leads to increased mortality, secondary resistance (including extensively drug-resistant tuberculosis), and ongoing transmission. 6 , 7 The complexity of mycobacterial culture and current nucleic acid–amplification technologies for the detection of tuberculosis and multidrug-resistant tuberculosis 8 and the . . .

Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings. We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%-85% to 95%-99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28-US$49 to US$133-US$146 and US$137-US$151 per TB case detected when Xpert is used \"in addition to\" and \"as a replacement of\" smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert \"in addition to\" smear microscopy, compared to the base case, range from US$41-$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert \"as a replacement of\" smear microscopy range from US$52-$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold. Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings.

The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2–3 sputum smears and 1–3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0–1), compared with 1 day (0–1) for microscopy, 30 days (23–43) for solid culture, and 16 days (13–21) for liquid culture. Median time to detection of resistance was 20 days (10–26) for line-probe assay and 106 days (30–124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39–81) to 5 days (2–8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.

Human infection with Mycobacterium tuberculosis can progress to active disease, be contained as latent infection, or be eradicated by the host response. Tuberculosis diagnostics classify a patient into one of these categories. These are not fixed distinct states, but rather are continua along which patients can move, and are affected by HIV infection, immunosuppressive therapies, antituberculosis treatments, and other poorly understood factors. Tuberculosis biomarkers—host or pathogen-specific—provide prognostic information, either for individual patients or study cohorts, about these outcomes. Tuberculosis case detection remains difficult, partly because of inaccurate diagnostic methods. Investments have yielded some progress in development of new diagnostics, although the existing pipeline is limited for tests for sputum-smear-negative cases, childhood tuberculosis, and accurate prediction of reactivation of latent tuberculosis. Despite new, sensitive, automated molecular platforms for detection of tuberculosis and drug resistance, a simple, inexpensive point-of-care test is still not available. The effect of any new tests will depend on the method and extent of their introduction, the strength of the laboratories, and the degree to which access to appropriate therapy follows access to diagnosis. Translation of scientific progress in biomarkers and diagnostics into clinical and public health programmes is possible—with political commitment, increased funding, and engagement of all stakeholders.

Background. Current malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections. Molecular methods such as polymerase chain reaction (PCR) are highly sensitive but remain too complex for field deployment. A new commercial molecular assay based on loop-mediated isothermal amplification (LAMP) was assessed for field use. Methods. Malaria LAMP (Eiken Chemical, Japan) was evaluated for samples from 272 outpatients at a rural Ugandan clinic and compared with expert microscopy, nested PCR, and quantitative PCR (qPCR). Two technicians performed the assay after 3 days of training, using 2 alternative blood sample-preparation methods and visual interpretation of results by fluorescence assay. Results. Compared with 3-well nested PCR, the sensitivity of both LAMP and single-well nested PCR was 90%; the microscopy sensitivity was 51%. For samples with a Plasmodium falciparum qPCR titer of ≥2 parasites//μL, LAMP sensitivity was 97.8% (95% confidence interval, 93.7%-99.5%). Most false-negative LAMP results involved samples with parasitemia levels detectable by 3-well nested PCR but very low or undetectable by qPCR. Conclusions. Malaria LAMP in a remote Ugandan clinic achieved sensitivity similar to that of single-well nested PCR in a United Kingdom reference laboratory. LAMP dramatically lowers the detection threshold achievable in malaria-endemic settings, providing a new tool for diagnosis, surveillance, and screening in elimination strategies.

Human infection with Mycobacterium tuberculosis can progress to active disease, be contained as latent infection, or be eradicated by the host response. Tuberculosis diagnostics classify a patient into one of these categories. These are not fixed distinct states, but rather are continua along which patients can move, and are affected by HIV infection, immunosuppressive therapies, antituberculosis treatments, and other poorly understood factors. Tuberculosis biomarkers-host or pathogen-specific-provide prognostic information, either for individual patients or study cohorts, about these outcomes. Tuberculosis case detection remains difficult, partly because of inaccurate diagnostic methods. Investments have yielded some progress in development of new diagnostics, although the existing pipeline is limited for tests for sputum-smear-negative cases, childhood tuberculosis, and accurate prediction of reactivation of latent tuberculosis. Despite new, sensitive, automated molecular platforms for detection of tuberculosis and drug resistance, a simple, inexpensive point-of-care test is still not available. The effect of any new tests will depend on the method and extent of their introduction, the strength of the laboratories, and the degree to which access to appropriate therapy follows access to diagnosis. Translation of scientific progress in biomarkers and diagnostics into clinical and public health programmes is possible-with political commitment, increased funding, and engagement of all stakeholders. [PUBLICATION ABSTRACT]

Healthcare priorities all too often ignore the importance of diagnostics for disease control and case management. The Ebola epidemic illustrates the folly of this attitude when few therapeutic or prophylactic interventions are available.