Serotype-specific correlates of protection for pneumococcal carriage: an analysis of immunity in 19 countries.

Background: Pneumococcal conjugate vaccines (PCVs) provide direct protection against disease in those vaccinated, and interrupt transmission through the prevention of nasopharyngeal carriage. Methods: We analysed immunogenicity data from 5224 infants who received PCV in prime-boost schedules. We defined any increase in antibody between the one-month post-priming visit and the booster dose as an indication of nasopharyngeal carriage ('seroincidence'). We calculated antibody concentrations using receiver-operator characteristic curves, and used generalised additive models to compute their protective efficacy against seroincidence. To support seroincidence as a marker of carriage, we compared seroincidence in a randomised immunogenicity trial in Nepal with the serotype-specific prevalence of carriage in the same community. Findings: In Nepalese infants, seroincidence of carriage closely correlated with serotype-specific carriage prevalence in the community. In the larger data set, antibody concentrations associated with seroincidence were lowest for serotypes 6B and 23F (0.50 µg/mL and 0.63 µg/mL respectively), and highest for serotypes 19F and 14 (2.54 µg/mL and 2.48 µg/mL respectively). The protective efficacy of antibody at these levels was 62% and 74% for serotypes 6B and 23F, and 87% and 84% for serotypes 19F and 14. Protective correlates were on average 2.15 times higher in low/lower middle income countries than in high/upper middle income countries (GMR 2.15, 95%CI 1.46-3.17, p=0.0024). Interpretation: Antibody concentrations associated with protection vary between serotypes. Higher antibody concentrations are required for protection in low-income countries. These findings are important for global vaccination policy, to interrupt transmission by protecting against carriage

Use-case scenarios for an anti-Cryptosporidium therapeutic.

Cryptosporidium is a widely distributed enteric parasite that has an increasingly appreciated pathogenic role, particularly in pediatric diarrhea. While cryptosporidiosis has likely affected humanity for millennia, its recent "emergence" is largely the result of discoveries made through major epidemiologic studies in the past decade. There is no vaccine, and the only approved medicine, nitazoxanide, has been shown to have efficacy limitations in several patient groups known to be at elevated risk of disease. In order to help frontline health workers, policymakers, and other stakeholders translate our current understanding of cryptosporidiosis into actionable guidance to address the disease, we sought to assess salient issues relating to clinical management of cryptosporidiosis drawing from a review of the literature and our own field-based practice. This exercise is meant to help inform health system strategies for improving access to current treatments, to highlight recent achievements and outstanding knowledge and clinical practice gaps, and to help guide research activities for new anti-Cryptosporidium therapies

Freezing and chemical preservatives alter the stable isotope values of carbon and nitrogen of the Asiatic clam (Corbicula fluminea)

We tested the impacts of most common sample preservation methods used for aquatic sample materials on the stable isotope ratios of carbon and nitrogen in clams, a typical baseline indicator organism for many aquatic food web studies utilising stable isotope analysis (SIA). In addition to common chemical preservatives ethanol and formalin, we also assessed the potential impacts of freezing on δ¹³C and δ¹⁵N values and compared the preserved samples against freshly dried and analysed samples. All preservation methods, including freezing, had significant impacts on δ¹³C and δ¹⁵N values and the effects in general were greater on the carbon isotope values (1.3-2.2% difference) than on the nitrogen isotope values (0.9-1.0% difference). However, the impacts produced by the preservation were rather consistent within each method during the whole 1 year experiment allowing these to be accounted for, if clams are intended for use in retrospective stable isotope studies

Hazard Analysis of Critical Control Points Assessment as a Tool to Respond to Emerging Infectious Disease Outbreaks

Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and indirect economic impacts arising from direct mortality and control programmes in over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the most widespread and expensive zoonotic disease recorded and continues to pose a global health threat. The aim of this research was to assess the potential of utilising Hazard Analysis of Critical Control Points (HACCP) assessments in providing a framework for a rapid response to emerging infectious disease outbreaks. This novel approach applies a scientific process, widely used in food production systems, to assess risks related to a specific emerging health threat within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI viruses within Vietnam’s domestic poultry trade and relate our findings to the existing literature. Our HACCP assessment identified poultry flock isolation, transportation, slaughter, preparation and consumption as critical control points for Vietnam’s domestic poultry trade. Introduction of the preventative measures highlighted through this HACCP evaluation would reduce the risks posed by HPAI viruses and pressure on the national economy. We conclude that this HACCP assessment provides compelling evidence for the future potential that HACCP analyses could play in initiating a rapid response to emerging infectious diseases

Etiology of the membrane potential of rat white fat adipocytes

The plasma membrane potential (Vm) is key to many physiological processes, however its ionic aetiology in white fat adipocytes is poorly characterised. To address this question, we have employed the perforated patch current-clamp and cell-attached patch-clamp methods in isolated primary white fat adipocytes and their cellular model: 3T3-L1. The resting Vm of primary and 3T3-L1 adipocytes were -32.1±1.2mV (n=95) and -28.8±1.2mV (n=87), respectively. Vm was independent of cell size and fat content. Elevation of extracellular [K+] to 50mM by equimolar substitution of bath Na+ did not affect Vm, whereas substitution of bath Na+ with the membrane impermeant cation N-methyl-D-glucamine+ hyperpolarized Vm by 16mV, data indicative of a non-selective cation permeability. Substitution of 133mM extracellular Cl- with gluconate, depolarised Vm to +5.5, whereas Cl- substitution with I- caused a -9mV hyperpolarization. Isoprenaline (10µM) but not insulin (100nM) significantly depolarized Vm. Single-channel ion activity was voltage independent; currents were indicative for Cl- with an inward slope conductance of 16±1.3pS (n=11) and a reversal potential close to the Cl- equilibrium potential: -29±1.6mV. Reduction of extracellular Cl- elevated the intracellular Ca2+ of adipocytes. In conclusion, the Vm of white fat adipocyte is well described by the Goldman-Hodgkin-Katz equation with a predominant permeability to Cl-. Consequently, changes in serum Cl- homeostasis or the adipocyte’s permeability to this anion via drugs will affect its Vm, intracellular Ca2+ and ultimately its function and its role in metabolic control

The Longitudinal Relationship Between Satisfaction with Transitional Care and Social and Emotional Quality of Life Among Chronically Ill Adolescents

This study aimed to identify the relationship between satisfaction with transitional care and quality of life of chronically ill adolescents over time. This longitudinal study included adolescents with type I diabetes, juvenile idiopathic arthritis (JIA), and neuromuscular disorders (NMD). At baseline 138 respondents (response rate 31 %) filled in a questionnaire and 188 about 1 year later (response rate 43 %). Analysis of variance showed that adolescents with diabetes reported the highest physical quality of life, followed in order by those with NMD and JIA (p ≤ 0.01). Adolescents with diabetes reported the highest social quality of life, followed in order by those with JIA and NMD (both at p ≤ 0.001). Univariate analyses showed that satisfaction with transitional care at T0 was significantly related to emotional and physical quality of life at T1 (both at p ≤ 0.05). At T1, satisfaction with transitional care was significantly related to the emotional, physical, and social domains of quality of life (all at p ≤ 0.001). Multiple regression analyses revealed that satisfaction with transitional care at T1 was related to emotional (β -0.20; p ≤ 0.05) and social (β -0.35; p ≤ 0.01) quality of life domains over time. This indicates that lower gap scores, which measured differences between 'best care' and 'current care,' are associated with better social and emotional quality of life in this sample of adolescents. Satisfaction with transitional care and social and emotional quality of life are related over time

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

How important is the context of an adolescent's first alcoholic drink? Evidence that parental provision may reduce later heavy episodic drinking

Objective: This study examined the extent to which a retrospective measure of parental provision of the first alcoholic beverage was related to current heavy episodic drinking and current responsible drinking practices. Sample: 608 14- to 17-year-olds from the 2007 Australian National Drug Strategy Household Survey. Measures: Source of first alcoholic beverage (friends/parents/others), source of current alcohol, age of onset of alcohol use, current responsible drinking practices, and proportion of current friends who drink. Results: Binary logistic and multiple regression procedures revealed that parental provision of an adolescent's first alcoholic beverage predicted lower current heavy episodic drinking, and responsible drinking mediated this association. Discussion: The results suggested that for adolescents who become alcohol users, parental provision of the first drink may reduce subsequent alcohol-related risks compared to introduction to alcohol by friends and other sources. Alcohol-related risks remain significant for adolescents who consume alcohol, independent of who is the provider. Copyright (C) 2012 S. Karger AG, Base

Visual parameter optimisation for biomedical image processing

Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships between input and output. Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by integrating input and output, and by supporting exploration of their relationships. We discuss its application to a colour deconvolution technique for stained histology images and show how it enabled a domain expert to identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying assumption about the algorithm. Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs in biomedical image processing that is not supported by previous analysis software. The analysis supported by our method is not feasible with conventional trial-and-error approaches

Sequential Effects in Judgements of Attractiveness: The Influences of Face Race and Sex

In perceptual decision-making, a person’s response on a given trial is influenced by their response on the immediately preceding trial. This sequential effect was initially demonstrated in psychophysical tasks, but has now been found in more complex, real-world judgements. The similarity of the current and previous stimuli determines the nature of the effect, with more similar items producing assimilation in judgements, while less similarity can cause a contrast effect. Previous research found assimilation in ratings of facial attractiveness, and here, we investigated whether this effect is influenced by the social categories of the faces presented. Over three experiments, participants rated the attractiveness of own- (White) and other-race (Chinese) faces of both sexes that appeared successively. Through blocking trials by race (Experiment 1), sex (Experiment 2), or both dimensions (Experiment 3), we could examine how sequential judgements were altered by the salience of different social categories in face sequences. For sequences that varied in sex alone, own-race faces showed significantly less opposite-sex assimilation (male and female faces perceived as dissimilar), while other-race faces showed equal assimilation for opposite- and same-sex sequences (male and female faces were not differentiated). For sequences that varied in race alone, categorisation by race resulted in no opposite-race assimilation for either sex of face (White and Chinese faces perceived as dissimilar). For sequences that varied in both race and sex, same-category assimilation was significantly greater than opposite-category. Our results suggest that the race of a face represents a superordinate category relative to sex. These findings demonstrate the importance of social categories when considering sequential judgements of faces, and also highlight a novel approach for investigating how multiple social dimensions interact during decision-making