Translation and Community in the work of Elizabeth Cary

Explores the role of female community within Elizabeth Cary\u27s translations and her play, The Tragedy of Mariam

Exposure-Response Estimates for Diesel Engine Exhaust and Lung Cancer Mortality Based on Data from Three Occupational Cohorts

Background: Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen. Objective: We derived a meta-exposure–response curve (ERC) for DEE and lung cancer mortality and estimated lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environmental exposure scenarios. Methods: We conducted a meta-regression of lung cancer mortality and cumulative exposure to elemental carbon (EC), a proxy measure of DEE, based on relative risk (RR) estimates reported by three large occupational cohort studies (including two studies of workers in the trucking industry and one study of miners). Based on the derived risk function, we calculated ELRs for several lifetime occupational and environmental exposure scenarios and also calculated the fractions of annual lung cancer deaths attributable to DEE. Results: We estimated a lnRR of 0.00098 (95% CI: 0.00055, 0.0014) for lung cancer mortality with each 1-μg/m3-year increase in cumulative EC based on a linear meta-regression model. Corresponding lnRRs for the individual studies ranged from 0.00061 to 0.0012. Estimated numbers of excess lung cancer deaths through 80 years of age for lifetime occupational exposures of 1, 10, and 25 μg/m3 EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 μg/m3 EC, we estimated 21 excess lung cancer deaths per 10,000. Based on broad assumptions regarding past occupational and environmental exposures, we estimated that approximately 6% of annual lung cancer deaths may be due to DEE exposure. Conclusions: Combined data from three U.S. occupational cohort studies suggest that DEE at levels common in the workplace and in outdoor air appear to pose substantial excess lifetime risks of lung cancer, above the usually acceptable limits in the United States and Europe, which are generally set at 1/1,000 and 1/100,000 based on lifetime exposure for the occupational and general population, respectively. Citation: Vermeulen R, Silverman DT, Garshick E, Vlaanderen J, Portengen L, Steenland K. 2014. Exposure-response estimates for diesel engine exhaust and lung cancer mortality based on data from three occupational cohorts. Environ Health Perspect 122:172–177; http://dx.doi.org/10.1289/ehp.130688

Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence

Activation of the endothelin A receptor (ETA) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ETA may have anticancer effects, while retaining beneficial endothelin B receptor (ETB)-mediated effects such as apoptosis and clearance of ET-1. ZD4054 is an orally active, specific ETA antagonist in clinical development. In receptor-binding studies, ZD4054 specifically bound to ETA with high affinity; no binding was detected at ETB. In a randomised placebo-controlled trial in eight healthy volunteers, a single oral dose of ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion of ET-1, thus providing clinical evidence of ETA blockade. ETB blockade was assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers. For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h were within the placebo reference range (a rise in ET-1 would indicate ETB blockade) and there was no evidence of dose-related changes. These data confirm the specificity of ZD4054 for ETA, with no activity at ETB in a clinical or preclinical setting. As a result of this specificity, ZD4054 has the potential to block multiple ETA-induced pathological processes, while allowing beneficial ETB-mediated processes to continue, which may, in turn, lead to an effective cancer therapy

Body Segment Differences in Surface Area, Skin Temperature and 3D Displacement and the Estimation of Heat Balance during Locomotion in Hominins

The conventional method of estimating heat balance during locomotion in humans and other hominins treats the body as an undifferentiated mass. This is problematic because the segments of the body differ with respect to several variables that can affect thermoregulation. Here, we report a study that investigated the impact on heat balance during locomotion of inter-segment differences in three of these variables: surface area, skin temperature and rate of movement. The approach adopted in the study was to generate heat balance estimates with the conventional method and then compare them with heat balance estimates generated with a method that takes into account inter-segment differences in surface area, skin temperature and rate of movement. We reasoned that, if the hypothesis that inter-segment differences in surface area, skin temperature and rate of movement affect heat balance during locomotion is correct, the estimates yielded by the two methods should be statistically significantly different. Anthropometric data were collected on seven adult male volunteers. The volunteers then walked on a treadmill at 1.2 m/s while 3D motion capture cameras recorded their movements. Next, the conventional and segmented methods were used to estimate the volunteers' heat balance while walking in four ambient temperatures. Lastly, the estimates produced with the two methods were compared with the paired t-test. The estimates of heat balance during locomotion yielded by the two methods are significantly different. Those yielded by the segmented method are significantly lower than those produced by the conventional method. Accordingly, the study supports the hypothesis that inter-segment differences in surface area, skin temperature and rate of movement impact heat balance during locomotion. This has important implications not only for current understanding of heat balance during locomotion in hominins but also for how future research on this topic should be approached

A new cell primo-culture method for freshwater benthic diatom communities

A new cell primo-culture method was developed for the benthic diatom community isolated from biofilm sampled in rivers. The approach comprised three steps: (1) scraping biofilm from river pebbles, (2) diatom isolation from biofilm, and (3) diatom community culture. With a view to designing a method able to stimulate the growth of diatoms, to limit the development of other microorganisms, and to maintain in culture a community similar to the original natural one, different factors were tested in step 3: cell culture medium (Chu No 10 vs Freshwater “WC” medium modified), cell culture vessel, and time of culture. The results showed that using Chu No 10 medium in an Erlenmeyer flask for cell culture was the optimal method, producing enough biomass for ecotoxicological tests as well as minimising development of other microorganisms. After 96 h of culture, communities differed from the original communities sampled in the two rivers studied. Species tolerant of eutrophic or saprobic conditions were favoured during culture. This method of diatom community culture affords the opportunity to assess, in vitro, the effects of different chemicals or effluents (water samples andindustrial effluents) on diatom communities, as well as on diatom cells, from a wide range of perspectives

Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain

<p>Abstract</p> <p>Background</p> <p>Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs.</p> <p>Results</p> <p>In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden.</p> <p>Conclusions</p> <p>Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.</p

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care

What's pain like?

La utilización de la terminología médica en inglés es vital para el desarrollo de las actividades docentes de los estudiantes de 4to. y 5to. año de Medicina y, sobre todo, en las actividades de Educación para el trabajo  que están estipuladas en el programa de las asignaturas Inglés VII, VIII, IX y X.Dentro de ella se encuentra la descripción de la sensación de dolor que incluye un amplio vocabulario que no aparece en los libros de texto de inglés, por lo cual realizamos una revisión minuciosa del tema.Este glosario contiene cincuenta y cinco términos actualizados, asociados con la sensación de dolor y sus equivalentes en Español, así como sesenta y ocho enfermedades o entidades, en las que aparece este léxico. Esta terminología es necesaria para los estudiantes como parte de su entrenamiento docente en inglés, considerando los objetivos de salida del médico general básico.Palabras claves: Dolor, Educación en el trabajo.</span

Neural processing of criticism and positive comments from relatives in individuals with schizotypal personality traits

Objectives. High negative expressed emotion by family members towards schizophrenia patients increases the risk of subsequent relapse. The study aimed to determine whether individuals with high schizotypy (HS) and low schizotypy (LS) would differ in activation of brain areas involved in cognitive control when listening to relative criticism