Explore the vast range of titles available.

\"This book traces how health care helped to build the postindustrial city into the \"medical metropolis,\" a city where health care plays a dominant role in its economy and identity\"-- Provided by publisher.

Throughout the Ebola virus disease (EVD) epidemic in West Africa, field laboratory testing for EVD has relied on complex, multi-step real-time reverse transcription PCR (RT-PCR) assays; an accurate sample-to-answer RT-PCR test would reduce time to results and potentially increase access to testing. We evaluated the performance of the Cepheid GeneXpert Ebola assay on clinical venipuncture whole blood (WB) and buccal swab (BS) specimens submitted to a field biocontainment laboratory in Sierra Leone for routine EVD testing by RT-PCR (\"Trombley assay\"). This study was conducted in the Public Health England EVD diagnostic laboratory in Port Loko, Sierra Leone, using residual diagnostic specimens remaining after clinical testing. EDTA-WB specimens (n = 218) were collected from suspected or confirmed EVD patients between April 1 and July 20, 2015. BS specimens (n = 71) were collected as part of a national postmortem screening program between March 7 and July 20, 2015. EDTA-WB and BS specimens were tested with Xpert (targets: glycoprotein [GP] and nucleoprotein [NP] genes) and Trombley (target: NP gene) assays in parallel. All WB specimens were fresh; 84/218 were tested in duplicate on Xpert to compare WB sampling methods (pipette versus swab); 43/71 BS specimens had been previously frozen. In all, 7/218 (3.2%) WB and 7/71 (9.9%) BS samples had Xpert results that were reported as \"invalid\" or \"error\" and were excluded, leaving 211 WB and 64 BS samples with valid Trombley and Xpert results. For WB, 22/22 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 84.6%-100%), and 181/189 Trombley-negative samples were Xpert-negative (specificity 95.8%, 95% confidence interval (CI) 91.8%-98.2%). Seven of the eight Trombley-negative, Xpert-positive (Xpert cycle threshold [Ct] range 37.7-43.4) WB samples were confirmed to be follow-up submissions from previously Trombley-positive EVD patients, suggesting a revised Xpert specificity of 99.5% (95% CI 97.0%-100%). For Xpert-positive WB samples (n = 22), Xpert NP Ct values were consistently lower than GP Ct values (mean difference -4.06, 95% limits of agreement -6.09, -2.03); Trombley (NP) Ct values closely matched Xpert NP Ct values (mean difference -0.04, 95% limits of agreement -2.93, 2.84). Xpert results (positive/negative) for WB sampled by pipette versus swab were concordant for 78/79 (98.7%) WB samples, with comparable Ct values for positive results. For BS specimens, 20/20 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 83.2%-100%), and 44/44 Trombley-negative samples were Xpert-negative (specificity 100%, 95% CI 92.0%-100%). This study was limited to testing residual diagnostic samples, some of which had been frozen before use; it was not possible to test the performance of the Xpert Ebola assay at point of care. The Xpert Ebola assay had excellent performance compared to an established RT-PCR benchmark on WB and BS samples in a field laboratory setting. Future studies should evaluate feasibility and performance outside of a biocontainment laboratory setting to facilitate expanded access to testing.

Elderly and sedentary individuals are particularly vulnerable to heat related illness. Short-term heat acclimation (STHA) can decrease both the physical and mental stress imposed on individuals performing tasks in the heat. However, the feasibility and efficacy of STHA protocols in an older population remains unclear despite this population being particularly vulnerable to heat illness. The aim of this systematic review was to investigate the feasibility and efficacy of STHA protocols (≤twelve days, ≥four days) undertaken by participants over fifty years of age. Academic Search Premier, CINAHL Complete, MEDLINE, APA PsycInfo, and SPORTDiscus were searched for peer reviewed articles. The search terms were; (heat* or therm*) N3 (adapt* or acclimati*) AND old* or elder* or senior* or geriatric* or aging or ageing. Only studies using primary empirical data and which included participants ≥50 years of age were eligible. Extracted data includes participant demographics (sample size, gender, age, height, weight, BMI and [Formula: see text]), acclimation protocol details (acclimation activity, frequency, duration and outcome measures taken) and feasibility and efficacy outcomes. Twelve eligible studies were included in the systematic review. A total of 179 participants took part in experimentation, 96 of which were over 50 years old. Age ranged from 50 to 76. All twelve of the studies involved exercise on a cycle ergometer. Ten out of twelve protocols used a percentage of [Formula: see text] or [Formula: see text] to determine the target workload, which ranged from 30% to 70%. One study-controlled workload at 6METs and one implemented an incremental cycling protocol until Tre was reached +0.9°C. Ten studies used an environmental chamber. One study compared hot water immersion (HWI) to an environmental chamber while the remaining study used a hot water perfused suit. Eight studies reported a decrease in core temperature following STHA. Five studies demonstrated post-exercise changes in sweat rates and four studies showed decreases in mean skin temperature. The differences reported in physiological markers suggest that STHA is viable in an older population. There remains limited data on STHA in the elderly. However, the twelve studies examined suggest that STHA is feasible and efficacious in elderly individuals and may provide preventative protection to heat exposures. Current STHA protocols require specialised equipment and do not cater for individuals unable to exercise. Passive HWI may provide a pragmatic and affordable solution, however further information in this area is required.

American Wild: it can kill you, or exhilarate you. It's always there, a character in its own right in the great unfolding narrative of American writing. This issue of Granta is dedicated to stories of the wild, from MELINDA MOUSTAKIS on gutting fish in Alaska to CLAIRE VAYE WATKINS on a lost child in a dystopian California. Also: ANTHONY DOERR on a family of pioneers in Idaho, ADAM NICOLSON on tracking wolves in New Mexico and DAVID TREUER on cage fighting and his Ojibwe heritage.

Key Points Cancer/testis (CT) antigens are normally expressed by gametes and trophoblasts, and are aberrantly expressed in a range of human cancers. So far, 44 distinct CT-antigen families, some of which have multiple members, have been identified. CT antigens are immunogenic and, as a result, have the potential to be used as tumour vaccines. CT antigens can be divided between those that are encoded on the X chromosome (CT-X antigens) and those that are not (non-X CT antigens). CT-X antigens tend to form recently expanded gene families that are usually highly expressed in the spermatogonia — mitotically proliferating germ cells. The CT-X genes are frequently co-expressed in cancer cells, which tend to express several CT antigens. The genes for the Non-X CT antigens are distributed throughout the genome. In the testis, they are usually expressed in the spermatocytes and many have roles in meiosis. Their aberrant expression in cancer cells might cause abnormal chromosome segregation and aneuploidy. Methylated CpG islands associated with the CT-X genes in normal somatic cells become demethylated in cancer cells, indicating activation of their expression. Although global hypomethylation is frequently put forward as the basis of CT-antigen expression in cancer cells, it will be important to define the events leading to the hypomethylated state. MAGEA1 has been shown to be a transcriptional co-repressor that interacts with SKI interacting protein and autonomously represses transcription. Other CT-X antigens also control gene expression and directly influence the sensitivity of cancer cell lines to cytotoxic assault as well as cell proliferation. As germline stem cells and their trophoblastic derivatives share many characteristics with tumour cells, the activation of normally silent germline-specific genes in cancer stem cells (gametic recapitulation) could mediate the malignant phenotype in the absence of mutations in known oncogenes and tumour-suppressor genes. Cancer/testis (CT) antigens, of which more than 40 have now been identified, are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumour types, including melanoma, and carcinomas of the bladder, lung and liver. These immunogenic proteins are being vigorously pursued as targets for therapeutic cancer vaccines. CT antigens are also being evaluated for their role in oncogenesis — recapitulation of portions of the germline gene-expression programme might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, hypomethylation and metastatic capacity.

Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in West Africa, disease control depends entirely on interrupting transmission through early disease detection and prompt patient isolation. Lateral Flow Immunoassays (LFI) are a potential supplement to centralized reference laboratory testing for the early diagnosis of Ebola Virus Disease (EVD). The goal of this study was to assess the performance of commercially available simple and rapid antigen detection LFIs, submitted for review to the WHO via the Emergency Use Assessment and Listing procedure. The study was performed in an Ebola Treatment Centre laboratory involved in EVD testing in Sierra Leone. In light of the current Ebola outbreak in May 2018 in the Democratic Republic of Congo, which highlights the lack of clarity in the global health community about appropriate Ebola diagnostics, our findings are increasingly critical. A cross-sectional study was conducted to assess comparative performance of four LFIs for detecting EVD. LFIs were assessed against the same 328 plasma samples and 100 whole EDTA blood samples, using the altona RealStar Filovirus Screen real-time RT-PCR as the bench mark assay. The performance of the Public Health England (PHE) in-house Zaire ebolavirus-specific real time RT-PCR Trombley assay was concurrently assessed. Statistical analysis using generalized estimating equations was conducted to compare LFI performance. Sensitivity and specificity varied between the LFIs, with specificity found to be significantly higher for whole EDTA blood samples compared to plasma samples in at least 2 LFIs (P≤0.003). Using the altona RT-PCR assay as the bench mark, sensitivities on plasma samples ranged from 79.53% (101/127, 95% CI: 71.46-86.17%) for the DEDIATEST EBOLA (SD Biosensor) to 98.43% (125/127, 95% CI: 94.43-99.81%) for the One step Ebola test (Intec). Specificities ranged from 80.20% (158/197, 95% CI: 74.07-88.60%) for plasma samples using the ReEBOV Antigen test Kit (Corgenix) to 100.00% (98/98, 95% CI: 96.31-100.00%) for whole blood samples using the DEDIATEST EBOLA (SD Biosensor) and SD Ebola Zaire Ag (SD Biosensor). Results also showed the Trombley RT-PCR assay had a lower limit of detection than the altona assay, with some LFIs having higher sensitivity than the altona assay when the Trombley assay was the bench mark. All of the tested EVD LFIs may be considered suitable for use in an outbreak situation (i.e. rule out testing in communities), although they had variable performance characteristics, with none possessing both high sensitivity and specificity. The non-commercial Trombley Zaire ebolavirus RT-PCR assay warrants further investigation, as it appeared more sensitive than the current gold standard, the altona Filovirus Screen RT-PCR assay.

Cancer/Testis (CT) genes, normally expressed in germ line cells but also activated in a wide range of cancer types, often encode antigens that are immunogenic in cancer patients, and present potential for use as biomarkers and targets for immunotherapy. Using multiple in silico gene expression analysis technologies, including twice the number of expressed sequence tags used in previous studies, we have performed a comprehensive genome-wide survey of expression for a set of 153 previously described CT genes in normal and cancer expression libraries. We find that although they are generally highly expressed in testis, these genes exhibit heterogeneous gene expression profiles, allowing their classification into testis-restricted (39), testis/brain-restricted (14), and a testis-selective (85) group of genes that show additional expression in somatic tissues. The chromosomal distribution of these genes confirmed the previously observed dominance of X chromosome location, with CT-X genes being significantly more testis-restricted than non-X CT. Applying this core classification in a genome-wide survey we identified >30 CT candidate genes; 3 of them, PEPP-2, OTOA, and AKAP4, were confirmed as testis-restricted or testis-selective using RT-PCR, with variable expression frequencies observed in a panel of cancer cell lines. Our classification provides an objective ranking for potential CT genes, which is useful in guiding further identification and characterization of these potentially important diagnostic and therapeutic targets.

TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Pan African Clinical Trials Registry PACTR201501000997429.