A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Verbal Learning and Memory in Cannabis and Alcohol Users: An Event-Related Potential Investigation

Aims: Long-term heavy use of cannabis and alcohol are known to be associated withmemory impairments. In this study, we used event-related potentials to examine verballearning and memory processing in a commonly used behavioral task.Method: We conducted two studies: first, a small pilot study of adolescent males,comprising 13 Drug-Naive Controls (DNC), 12 heavy drinkers (HD) and 8 cannabis users(CU). Second, a larger study of young adults, comprising 45 DNC (20 female), 39 HD (16female), and 20 CU (9 female). In both studies, participants completed a modified verballearning task (the Rey Auditory Verbal Learning Test, RAVLT) while brain electrical activitywas recorded. ERPs were calculated for words which were subsequently rememberedvs. those which were not remembered, and for presentations of learnt words, previouslyseen words, and new words in a subsequent recognition test. Pre-planned principalcomponents analyses (PCA) were used to quantify the ERP components in these recalland recognition phases separately for each study.Results: Memory performance overall was slightly lower than published norms usingthe standardized RAVLT delivery, but was generally similar and showed the expectedchanges over trials. Few differences in performance were observed between groups; anotable exception was markedly poorer delayed recall in HD relative to DNC (Study 2).PCA identified components expected from prior research using other memory tasks. Atencoding, there were no between-group differences in the usual P2 recall effect (larger forrecalled than not-recalled words). However, alcohol-related differences were observed ina larger P540 (indexing recollection) in HD than DNC, and cannabis-related differenceswere observed in a smaller N340 (indexing familiarity) and a lack of previously seen > newwords effect for P540 in Study 2.Conclusions: This study is the first examination of ERPs in the RAVLT in healthycontrol participants, as well as substance-using individuals, and represents an importantadvance in methodology. The results indicate alterations in recognition memoryprocessing, which even if not manifesting in overt behavioral impairment, underline thepotential for brain dysfunction with early exposure to alcohol and cannabis

How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

Impact of adiposity on cardiac structure in adult life: the Childhood Determinants of Adult Health (CDAH) study.

BACKGROUND: We have examined the association between adiposity and cardiac structure in adulthood, using a life course approach that takes account of the contribution of adiposity in both childhood and adulthood. METHODS: The Childhood Determinants of Adult Health study (CDAH) is a follow-up study of 8,498 children who participated in the 1985 Australian Schools Health and Fitness Survey (ASHFS). The CDAH follow-up study included 2,410 participants who attended a clinic examination. Of these, 181 underwent cardiac imaging and provided complete data. The measures were taken once when the children were aged 9 to 15 years, and once in adult life, aged 26 to 36 years. RESULTS: There was a positive association between adult left ventricular mass (LVM) and childhood body mass index (BMI) in males (regression coefficient (β) 0.41; 95% confidence interval (CI): 0.14 to 0.67; p = 0.003), and females (β = 0.53; 95% CI: 0.34 to 0.72; p < 0.001), and with change in BMI from childhood to adulthood (males: β = 0.27; 95% CI: 0.04 to 0.51; p < 0.001, females: β = 0.39; 95% CI: 0.20 to 0.58; p < 0.001), after adjustment for confounding factors (age, fitness, triglyceride levels and total cholesterol in adulthood). After further adjustment for known potential mediating factors (systolic BP and fasting plasma glucose in adulthood) the relationship of LVM with childhood BMI (males: β = 0.45; 95% CI: 0.19 to 0.71; p = 0.001, females: β = 0.49; 95% CI: 0.29 to 0.68; p < 0.001) and change in BMI (males: β = 0.26; 95% CI: 0.04 to 0.49; p = 0.02, females: β = 0.40; 95% CI: 0.20 to 0.59; p < 0.001) did not change markedly. CONCLUSIONS: Adiposity and increased adiposity from childhood to adulthood appear to have a detrimental effect on cardiac structure

Women on boards and firm performance

This study investigates the financial performance of Dutch companies both with and without women on their boards. The analysis extends earlier methods used in research by Catalyst (The bottom line: corporate performance and women's representation on boards, 2007) and McKinsey (Women matter. Gender diversity, a corporate performance driver. McKinsey & Company, USA, 2007), two studies that are often cited in the literature, although, each has a number of methodological shortcomings. This article adds to the international debate, which is often normative, through examining 99 listed companies in the Dutch Female Board Index. Our results show that firms with women directors perform better than those without women on their boards

Planetary bearing defect detection in a commercial helicopter main gearbox with vibration and acoustic emission

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Helicopter gearboxes significantly differ from other transmission types and exhibit unique behaviors that reduce the effectiveness of traditional fault diagnostics methods. In addition, due to lack of redundancy, helicopter transmission failure can lead to catastrophic accidents. Bearing faults in helicopter gearboxes are difficult to discriminate due to the low signal to noise ratio (SNR) in the presence of gear vibration. In addition, the vibration response from the planet gear bearings must be transmitted via a time-varying path through the ring gear to externally mounted accelerometers, which cause yet further bearing vibration signal suppression. This research programme has resulted in the successful proof of concept of a broadband wireless transmission sensor that incorporates power scavenging whilst operating within a helicopter gearbox. In addition, this paper investigates the application of signal separation techniques in detection of bearing faults within the epicyclic module of a large helicopter (CS-29) main gearbox using vibration and Acoustic Emissions (AE). It compares their effectiveness for various operating conditions. Three signal processing techniques including an adaptive filter, spectral kurtosis and envelope analysis, were combined for this investigation. In addition, this research discusses the feasibility of using AE for helicopter gearbox monitoring

Reduced Population Control of an Insect Pest in Managed Willow Monocultures

BACKGROUND: There is a general belief that insect outbreak risk is higher in plant monocultures than in natural and more diverse habitats, although empirical studies investigating this relationship are lacking. In this study, using density data collected over seven years at 40 study sites, we compare the temporal population variability of the leaf beetle Phratora vulgatissima between willow plantations and natural willow habitats. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in 1999-2005. The density of adult P. vulgatissima was estimated in the spring every year by a knock-down sampling technique. We used two measures of population variability, CV and PV, to compare temporal variations in leaf beetle density between plantation and natural habitat. Relationships between density and variability were also analyzed to discern potential underlying processes behind stability in the two systems. The results showed that the leaf beetle P. vulgatissima had a greater temporal population variability and outbreak risk in willow plantations than in natural willow habitats. We hypothesize that the greater population stability observed in the natural habitat was due to two separate processes operating at different levels of beetle density. First, stable low population equilibrium can be achieved by the relatively high density of generalist predators observed in natural stands. Second, stable equilibrium can also be imposed at higher beetle density due to competition, which occurs through depletion of resources (plant foliage) in the natural habitat. In willow plantations, competition is reduced mainly because plants grow close enough for beetle larvae to move to another plant when foliage is consumed. CONCLUSION/SIGNIFICANCE: To our knowledge, this is the first empirical study confirming that insect pest outbreak risk is higher in monocultures. The study suggests that comparative studies of insect population dynamics in different habitats may improve our ability to predict insect pest outbreaks and could facilitate the development of sustainable pest control in managed systems

Continuum Molecular Simulation of Large Conformational Changes during Ion–Channel Gating

A modeling framework was developed to simulate large and gradual conformational changes within a macromolecule (protein) when its low amplitude high frequency vibrations are not concerned. Governing equations were derived as alternative to Langevin and Smoluchowski equations and used to simulate gating conformational changes of the Kv7.1 ion-channel over the time scale of its gating process (tens of milliseconds). The alternative equations predict the statistical properties of the motion trajectories with good accuracy and do not require the force field to be constant over the diffusion length, as assumed in Langevin equation. The open probability of the ion–channel was determined considering cooperativity of four subunits and solving their concerted transition to the open state analytically. The simulated open probabilities for a series of voltage clamp tests produced current traces that were similar to experimentally recorded currents

Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases

Current antibiotics tend to be broad spectrum, leading to indiscriminate killing of commensal bacteria and accelerated evolution of drug resistance. Here, we use CRISPR-Cas technology to create antimicrobials whose spectrum of activity is chosen by design. RNA-guided nucleases (RGNs) targeting specific DNA sequences are delivered efficiently to microbial populations using bacteriophage or bacteria carrying plasmids transmissible by conjugation. The DNA targets of RGNs can be undesirable genes or polymorphisms, including antibiotic resistance and virulence determinants in carbapenem-resistant Enterobacteriaceae and enterohemorrhagic Escherichia coli. Delivery of RGNs significantly improves survival in a Galleria mellonella infection model. We also show that RGNs enable modulation of complex bacterial populations by selective knockdown of targeted strains based on genetic signatures. RGNs constitute a class of highly discriminatory, customizable antimicrobials that enact selective pressure at the DNA level to reduce the prevalence of undesired genes, minimize off-target effects and enable programmable remodeling of microbiota.National Institutes of Health (U.S.) (New Innovator Award 1DP2OD008435)National Centers for Systems Biology (U.S.) (Grant 1P50GM098792)United States. Defense Threat Reduction Agency (HDTRA1-14-1-0007)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (W911NF13D0001)National Institute of General Medical Sciences (U.S.) (Interdepartmental Biotechnology Training Program 5T32 GM008334)Fonds de la recherche en sante du Quebec (Master's Training Award