The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n = 290; aged 9–13 years) born to participants in a cluster-randomized trial of maternal vitamin A or β-carotene supplementation in rural Nepal (1994–1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (β = 0.02; P = 0.05) and higher concentrations among children born to β-carotene-supplemented mothers (β = 0.19; P < 0.05). At ∼9–12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (β = 0.02; P < 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (β = −0.13; P = 0.15), during the monsoon (β = −0.22; P = 0.04), and pre-harvest (β = −0.34; P = 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.

Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.

Prior research has established associations between neighbourhood poverty and cumulative biological risk (CBR). CBR is conceptualized as indicative of the effects of stress on biological functioning, and is linked with increased morbidity and mortality. Studies suggest that supportive social relationships may be health protective, and may erode under conditions of poverty. This study examines whether social relationships are inversely associated with CBR and whether associations between neighbourhood poverty and CBR are mediated through social relationships. Data were from a stratified probability sample community survey (n=919) of residents of Detroit, Michigan, USA (2002–2003) and from the 2000 US Census. The outcome variable, CBR, included anthropometric and clinical measures. Independent variables included four indicators of social relationships: social support, neighbourhood satisfaction, social cohesion and neighbourhood participation. Multilevel models were used to test both research questions, with neighbourhood poverty and social relationships included at the block group level, and social relationships also included at the individual level, to disentangle individual from neighbourhood effects. Findings suggest some associations between social relationships and CBR after accounting for neighbourhood poverty and individual characteristics. In models that accounted for all indicators of social relationships, individual-level social support was associated with greater CBR (β=0.12, p=0.04), while neighbourhood-level social support was marginally significantly protective of CBR (within-neighbourhood: β=−0.36, p=0.06; between-neighbourhood: β=−0.24, p=0.06). In contrast, individual-level neighbourhood satisfaction was protective of CBR (β=−0.10, p=0.02), with no within-neighbourhood (β=0.06, p=0.54) or between-neighbourhood association (β=−0.04, p=0.38). Results indicate no significant association between either social cohesion or neighbourhood participation and CBR. Associations between neighbourhood poverty and CBR were not mediated by social relationships. These findings suggest that neighbourhood-level social support and individual-level neighbourhood satisfaction may be health protective and that neighbourhood poverty, social support and neighbourhood satisfaction are associated with CBR through independent pathways.

Background: Graduating residents require general palliative care skills. In Canada, there is no standardized palliative care curriculum for specialty trained residents. The objective of this research is to develop an evidence-based palliative care curriculum designed to provide neurology residents with the general palliative care skills required for providing patient care along the continuum of life. Methods: A needs assessment was performed in Neurology at Western University using qualitative analysis techniques. Residents completed the following:. A curricular outline was developed based on the Kolb learning style inventory (LSI), a knowledge pre-test, the Palliative Medicine Comfort and Confidence Survey and a review of the literature. Two iterations of the curriculum have been developed. Results: Residents identified a need for additional training in supportive and palliative care skills. Based on the Kolb LSI, 9/16 (56.3%) of neurology residents are “accommodators”. General principles identified for inclusion included: symptom management, communication, psychosocial aspects of care, care coordination and access, and myths and pitfalls in palliative care. Conclusions: This project is designed to identify the current palliative educational needs for Neurology residents. The results suggest that specialty trained residents are receptive to embedding training in the principles of palliative care within their training programs.

Environmental enteric dysfunction (EED) and systemic inflammation (SI) are common in developing countries and may cause stunting. In Bangladesh, >40 % of preschool children are stunted, but EED and SI contributions are unknown. We aimed to determine the impact of EED and SI (assessed with multiple indicators) on growth in children (n 539) enrolled in a community-based randomised food supplementation trial in rural Bangladesh. EED was defined with faecal myeloperoxidase, α-1 antitrypsin and neopterin and serum endotoxin core antibody and glucagon-like peptide-2, consolidated into gut inflammation (GI) and permeability (GP) scores, and urinary lactulose:mannitol α-1 acid glycoprotein (AGP) characterised SI. Biomarker associations with anthropometry (15-, 18- and 24-month length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z scores) were examined in pairwise correlations and adjusted mixed-effects regressions. Stunting, wasting and underweight prevalence at 18 months were 45, 15 and 37 %, respectively, with elevated EED and SI markers common. EED and SI were not associated with 15–24-month length trajectory. Elevated (worse) GI and GP scores predicted reduced 18–24-month WLZ change (β −0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15–18-month WLZ change (β −0·03 (se 0·01) z score/month) and greater 15-month WLZ (β 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (β −0·04 (se 0·01) and β 0·02 (se 0·00) z score/month for 15–18 and 18–24 months). The hypothesised link from EED to stunting was not observed in this sample of Bangladeshi 18-month-olds, but the effects of EED on constrained weight gain may have consequences for later linear growth or for other health and development outcomes.

We present results from a multiwavelength study of the blazar PKS 1954–388 at radio, UV, X-ray, and gamma-ray energies. A RadioAstron observation at 1.66 GHz in June 2012 resulted in the detection of interferometric fringes on baselines of 6.2 Earth-diameters. This suggests a source frame brightness temperature of greater than 2 × 1012 K, well in excess of both equipartition and inverse Compton limits and implying the existence of Doppler boosting in the core. An 8.4-GHz TANAMI VLBI image, made less than a month after the RadioAstron observations, is consistent with a previously reported superluminal motion for a jet component. Flux density monitoring with the Australia Telescope Compact Array confirms previous evidence for long-term variability that increases with observing frequency. A search for more rapid variability revealed no evidence for significant day-scale flux density variation. The ATCA light-curve reveals a strong radio flare beginning in late 2013, which peaks higher, and earlier, at higher frequencies. Comparison with the Fermi gamma-ray light-curve indicates this followed ~ 9 months after the start of a prolonged gamma-ray high-state—a radio lag comparable to that seen in other blazars. The multiwavelength data are combined to derive a Spectral Energy Distribution, which is fitted by a one-zone synchrotron-self-Compton (SSC) model with the addition of external Compton (EC) emission.

Hypocrisy challenges religious belief in two ways. Arguments to Absurdity contend hypocrisy is defeasible evidence of the irrationality of a doctrine or practice. Arguments from Betrayal contend that hypocrisy confronts institutionally loyal believers with a tragic dilemma: that because loyalty is justified by the goodness of its object, hypocrisy requires believers to sacrifice either their conscience (to remain loyal) or their character and identity (by abandoning their loyalty). This article presents philosophical and theological reasons that both arguments are unpersuasive.

The bearded fireworm, Hermodice carunculata, is a common species in the marine annelid taxon Amphinomidae. It has a widespread distribution throughout the Atlantic, Gulf of Mexico, the Caribbean, Mediterranean and Red Seas. We review its environmental tolerances, defence mechanisms and feeding habits to evaluate its potential to survive in changing ocean conditions, to increasingly emerge as a nuisance species and to invade new geographic areas. Hermodice carunculata tolerates a wide range of environmental conditions, including temperature, salinity, oxygen saturation and various types of pollution. It has few natural predators because it is protected by its sharp chaetae and probably by toxins. Hermodice carunculata is best known for consuming live cnidarians, and has been implicated in transmitting coral pathogens, but it also feeds non-selectively on detritus. In the short term, we predict that H. carunculata will be able to withstand many future ecological challenges and possibly contribute to coral reef decline. In the long term, ocean acidification may negatively impact its defence mechanisms and survival. Its invasive potential may be significant. We highlight the gaps in our knowledge about the reproduction and development of this species, the nature and origin of its toxins and role of microbes in their feeding behaviour and defensive strategies.

A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.