Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality.

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics

Determinants of Influenza Mortality Trends: Age-Period-Cohort Analysis of Influenza Mortality in the United States, 1959-2016.

This study examines the roles of age, period, and cohort in influenza mortality trends over the years 1959-2016 in the United States. First, we use Lexis surfaces based on Serfling models to highlight influenza mortality patterns as well as to identify lingering effects of early-life exposure to specific influenza virus subtypes (e.g., H1N1, H3N2). Second, we use age-period-cohort (APC) methods to explore APC linear trends and identify changes in the slope of these trends (contrasts). Our analyses reveal a series of breakpoints where the magnitude and direction of birth cohort trends significantly change, mostly corresponding to years in which important antigenic drifts or shifts took place (i.e., 1947, 1957, 1968, and 1978). Whereas child, youth, and adult influenza mortality appear to be influenced by a combination of cohort- and period-specific factors, reflecting the interaction between the antigenic experience of the population and the evolution of the influenza virus itself, mortality patterns of the elderly appear to be molded by broader cohort factors. The latter would reflect the processes of physiological capital improvement in successive birth cohorts through secular changes in early-life conditions. Antigenic imprinting, cohort morbidity phenotype, and other mechanisms that can generate the observed cohort effects, including the baby boom, are discussed

Induction of fish biomarkers by synthetic-based drilling muds

The study investigated the effects of chronic exposure of pink snapper (Pagrus auratus Forster), to synthetic based drilling muds (SBMs). Fish were exposed to three mud systems comprised of three different types of synthetic based fluids (SBFs): an ester (E), an isomerized olefin (IO) and linear alpha olefin (LAO). Condition factor (CF), liver somatic index (LSI), hepatic detoxification (EROD activity), biliary metabolites, DNA damage and stress proteins (HSP-70) were determined. Exposure to E caused biologically significant effects by increasing CF and LSI, and triggered biliary metabolite accumulation. While ester-based SBFs have a rapid biodegradation rate in the environment, they caused the most pronounced effects on fish health. IO induced EROD activity and biliary metabolites and LAO induced EROD activity and stress protein levels. The results demonstrate that while acute toxicity of SBMs is generally low, chronic exposure to weathering cutting piles has the potential to affect fish health. The study illustrates the advantages of the Western Australian government case-by-case approach to drilling fluid management, and highlights the importance of considering the receiving environment in the selection of SBMs

Development and formative evaluation of the e-Health implementation toolkit

<b>Background</b> The use of Information and Communication Technology (ICT) or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice). This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT) which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format.<p></p> <b>Results</b> The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience). Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls<p></p> <b>Conclusions</b> The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations

Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

Phosphorylation and Transport in the Na-K-2Cl Cotransporters, NKCC1 and NKCC2A, Compared in HEK-293 Cells

Na-K-2Cl cotransporters help determine cell composition and volume. NKCC1 is widely distributed whilst NKCC2 is only found in the kidney where it plays a vital role reabsorbing 20% of filtered NaCl. NKCC2 regulation is poorly understood because of its restricted distribution and difficulties with its expression in mammalian cell cultures. Here we compare phosphorylation of the N-termini of the cotransporters, measured with phospho-specific antibodies, with bumetanide-sensitive transport of K+ (86Rb+) (activity) in HEK-293 cells stably expressing fNKCC1 or fNKCC2A which were cloned from ferret kidney. Activities of transfected transporters were distinguished from those of endogenous ones by working at 37°C. fNKCC1 and fNKCC2A activities were highest after pre-incubation of cells in hypotonic low-[Cl−] media to reduce cell [Cl−] and volume during flux measurement. Phosphorylation of both transporters more than doubled. Pre-incubation with ouabain also strongly stimulated fNKCC1 and fNKCC2A and substantially increased phosphorylation, whereas pre-incubation in Na+-free media maximally stimulated fNKCC1 and doubled its phosphorylation, but inhibited fNKCC2A, with a small increase in its phosphorylation. Kinase inhibitors halved phosphorylation and activity of both transporters whereas inhibition of phosphatases with calyculin A strongly increased phosphorylation of both transporters but only slightly stimulated fNKCC1 and inhibited fNCCC2A. Thus kinase inhibition reduced phosphorylation and transport, and transport stimulation was only seen when phosphorylation increased, but transport did not always increase with phosphorylation. This suggests phosphorylation of the N-termini determines the transporters' potential capacity to move ions, but final activity also depends on other factors. Transport cannot be reliably inferred solely using phospho-specific antibodies on whole-cell lysates

From theory to 'measurement' in complex interventions: methodological lessons from the development of an e-health normalisation instrument

<b>Background</b> Although empirical and theoretical understanding of processes of implementation in health care is advancing, translation of theory into structured measures that capture the complex interplay between interventions, individuals and context remain limited. This paper aimed to (1) describe the process and outcome of a project to develop a theory-based instrument for measuring implementation processes relating to e-health interventions; and (2) identify key issues and methodological challenges for advancing work in this field.<p></p> <b>Methods</b> A 30-item instrument (Technology Adoption Readiness Scale (TARS)) for measuring normalisation processes in the context of e-health service interventions was developed on the basis on Normalization Process Theory (NPT). NPT focuses on how new practices become routinely embedded within social contexts. The instrument was pre-tested in two health care settings in which e-health (electronic facilitation of healthcare decision-making and practice) was used by health care professionals.<p></p> <b>Results</b> The developed instrument was pre-tested in two professional samples (N = 46; N = 231). Ratings of items representing normalisation 'processes' were significantly related to staff members' perceptions of whether or not e-health had become 'routine'. Key methodological challenges are discussed in relation to: translating multi-component theoretical constructs into simple questions; developing and choosing appropriate outcome measures; conducting multiple-stakeholder assessments; instrument and question framing; and more general issues for instrument development in practice contexts.<p></p> <b>Conclusions</b> To develop theory-derived measures of implementation process for progressing research in this field, four key recommendations are made relating to (1) greater attention to underlying theoretical assumptions and extent of translation work required; (2) the need for appropriate but flexible approaches to outcomes measurement; (3) representation of multiple perspectives and collaborative nature of work; and (4) emphasis on generic measurement approaches that can be flexibly tailored to particular contexts of study

The Human Frontal Oculomotor Cortical Areas Contribute Asymmetrically to Motor Planning in a Gap Saccade Task

BACKGROUND: Saccadic eye movements are used to rapidly align the fovea with the image of objects of interest in peripheral vision. We have recently shown that in children there is a high preponderance of quick latency but poorly planned saccades that consistently fall short of the target goal. The characteristics of these multiple saccades are consistent with a lack of proper inhibitory control of cortical oculomotor areas on the brainstem saccade generation circuitry. METHODOLOGY/PRINCIPAL FINDINGS: In the present paper, we directly tested this assumption by using single pulse transcranial magnetic stimulation (TMS) to transiently disrupt neuronal activity in the frontal eye fields (FEF) and supplementary eye fields (SEF) in adults performing a gap saccade task. The results showed that the incidence of multiple saccades was increased for ispiversive but not contraversive directions for the right and left FEF, the left SEF, but not for the right SEF. Moreover, this disruption was most substantial during the approximately 50 ms period around the appearance of the peripheral target. A control condition in which the dorsal motor cortex was stimulated demonstrated that this was not due to any non-specific effects of the TMS influencing the spatial distribution of attention. CONCLUSIONS/SIGNIFICANCE: Taken together, the results are consistent with a direction-dependent role of the FEF and left SEF in delaying the release of saccadic eye movements until they have been fully planned

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Plasma response to fish oil in the elderly

Little information is available concerning whether incorporation of dietary omega-3 fatty acids into plasma lipids changes during healthy aging. Elderly (74 ± 4 years old) and young (24 ± 2 years old) adults were given a fish oil supplement for 3 weeks that provided 680 mg/day of docosahexaenoic acid and 320 mg/day of eicosapentaenoic acid, followed by a 2 week wash-out period. Compliance was monitored by spiking the capsules with carbon-13 glucose, the excretion of which was measured in breath CO2. In response to the supplement, plasma docosahexaenoic acid rose 42% more in the elderly but eicosapentaenoic responded similarly in both groups. Despite raising docosahexaenoic acid intake by five to tenfold, the supplement did not raise plasma free docosahexaenoic acid (% or mg/dL) in either group. We conclude that healthy aging is accompanied by subtle but significant changes in DHA incorporation into plasma lipids