Challenges to estimating vaccine impact using hospitalization data.

Because the real-world impact of new vaccines cannot be known before they are implemented in national programs, post-implementation studies at the population level are critical. Studies based on analysis of hospitalization rates of vaccine-preventable outcomes are typically used for this purpose. However, estimates of vaccine impact based on hospitalization data are particularly prone to confounding, as hospitalization rates are tightly linked to changes in the quality, access and use of the healthcare system, which often occur simultaneously with introduction of new vaccines. Here we illustrate how changes in healthcare delivery coincident with vaccine introduction can influence estimates of vaccine impact, using as an example reductions in infant pneumonia hospitalizations after introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) in Brazil. To this end, we explore the effect of changes in several metrics of quality and access to public healthcare on trends in hospitalization rates before (2008-09) and after (2011-12) PCV10 introduction in 2010. Changes in infant pneumonia hospitalization rates following vaccine introduction were significantly associated with concomitant changes in hospital capacity and the fraction of the population using public hospitals. Importantly, reduction of pneumonia hospitalization rates after PCV10 were also associated with the expansion of outpatient services in several Brazilian states, falling more sharply where primary care coverage and the number of health units offering basic and emergency care increased more. We show that adjustments for unrelated (non-vaccine) trends commonly employed by impact studies, such as use of single control outcomes, are not always sufficient for accurate impact assessment. We discuss several ways to identify and overcome such biases, including sensitivity analyses using different denominators to calculate hospitalizations rates and methods that track changes in the outpatient setting. Employing these practices can improve the accuracy of vaccine impact estimates, particularly in evolving healthcare settings typical of low- and middle-income countries

Unintended Pregnancies in Brazil - A Challenge for the Recommendation to Delay Pregnancy Due to Zika

Because of the potential link between the ongoing Zika virus outbreak and a surge in the number of cases of congenital microcephaly, officials in Latin America have recommended that women postpone pregnancy until this association is firmly established or the outbreak subsides. However, in all these countries a large proportion of babies are still born out of unplanned pregnancies. Teenage girls are particularly at high risk, as they often lack access to preventive contraception methods, or the knowledge to use them appropriately. To gauge the magnitude of the barriers preventing the implementation of such a recommendation in Brazil, the country so far most affected by the Zika epidemic, we evaluated pregnancy rates in teenage girls, and their spatial heterogeneity in the country, in recent years (2012-2014). Nearly 20% of children born in Brazil today (~560,000 live births) are by teenage mothers. Birth incidence is far higher in the tropical and poorer northern states. However, in absolute terms most births occur in the populous southeastern states, matching to a large extent the geographic distribution of dengue (an indicator of suitable climatic and sociodemographic conditions for the circulation of Aedes mosquitoes). These findings indicate that recommendation to delay pregnancy will leave over half a million pregnant adolescents in Brazil vulnerable to infection every year if not accompanied by effective education and real access to prevention

Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations

High-quality draft genome sequence of <i>Sphaerisporangium cinnabarinum</i> ATCC 31213

ABSTRACT A high-quality draft genome sequence of Sphaerisporangium cinnabarinum ATCC 31213 is presented here. This bacterium produces several important bioactive compounds and may also produce functional amyloids. This is the first sequenced genome from the genus Sphaerisporangium , and it will be essential in determining the nature of the potential amyloid protein. </jats:p

In for a penny, in for a pound: methylphenidate reduces the inhibitory effect of high stakes on persistent risky choice

Methylphenidate (MPH) is a stimulant that increases extracellular levels of dopamine and noradrenaline. It can diminish risky decision-making tendencies in certain clinical populations. MPH is also used, without license, by healthy adults, but the impact on their decision-making is not well established. Previous work has found that dopamine receptor activity of healthy adults can modulate the influence of stake magnitude on decisions to persistently gamble after incurring a loss. In this study, we tested for modulation of this effect by MPH in 40 healthy human adults. In a double-blind experiment, 20 subjects received 20 mg of MPH, while 20 matched controls received a placebo. All were provided with 30 rounds of opportunities to accept an incurred loss from their assets or opt for a "double-or-nothing" gamble that would either avoid or double it. Rounds began with a variable loss that would double with every failed gamble until it was accepted, recovered, or reached a specified maximum. Probability of recovery on any gamble was low and ambiguous. Subjects receiving placebo gambled less as the magnitude of the stake was raised and as the magnitude of accumulated loss escalated over the course of the task. In contrast, subjects treated with MPH gambled at a consistent rate, well above chance, across all stakes and trials. Trait reward responsiveness also reduced the impact of high stakes. The findings suggest that elevated catecholamine activity by MPH can disrupt inhibitory influences on persistent risky choice in healthy adults

A Influência do Nível de Competências e de Maturidade em Gestão de Projetos no Resultado Corporativo de uma Empresa do Setor de Transformação

The knowledge and project management practices contribute to the strategic execution and the maturity of these methodologies increases significantly the probability of success project. Even though, corporations, which instilled this methodology on their strategies, have tabled a number of projects showing less than satisfactory outcomes, due to set of factors linked to management and to corporate strategy implanted. This article aims to analyze the influence of competence and maturity in project management of matrix teams and managers in the results of projects and therefore on the corporate results. The research is qualitative, based on the method of single case study. The main results indicate the existence of a strong influence between skills and maturity in project management in operating performance and results of the organization. Os conhecimentos e as práticas em gestão de projetos contribuem para a execução estratégica, e a maturidade na aplicação dessa metodologia aumenta significativamente a probabilidade do sucesso de um projeto. Ainda assim, empresas que adotaram a gestão de projetos em sua estratégia têm apresentado uma série de projetos com resultados abaixo do nível satisfatório, em razão de um conjunto de fatores vinculados tanto à gestão quanto à estratégia corporativa. Neste artigo, o objetivo é analisar a influência das competências e da maturidade em gestão de projetos das equipes matriciais e dos gerentes no desempenho dos projetos e, consequentemente, no resultado corporativo. A pesquisa é qualitativa, baseada no método de estudo de caso único realizado em empresa do setor de indústrias de transformação. Os principais resultados apontam para a existência de forte influência das competências e maturidade em gestão de projetos no desempenho operacional e nos resultados da organização

Independent neural computation of value from other people's confidence

Expectation of reward can be shaped by the observation of actions and expressions of other people in one's environment. A person's apparent confidence in the likely reward of an action, for instance, makes qualities of their evidence, not observed directly, socially accessible. This strategy is computationally distinguished from associative learning methods that rely on direct observation, by its use of inference from indirect evidence. In twenty-three healthy human subjects, we isolated effects of first-hand experience, other people's choices, and the mediating effect of their confidence, on decision-making and neural correlates of value within ventromedial prefrontal cortex (vmPFC). Value derived from first hand experience and other people's choices (regardless of confidence) were indiscriminately represented across vmPFC. However, value computed from agent choices weighted by their associated confidence was represented with specificity for ventromedial area 10. This pattern corresponds to shifts of connectivity and overlapping cognitive processes along a posterior-anterior vmPFC axis. Task behavior and self-reported self-reliance for decision-making in other social contexts correlated. The tendency to conform in other social contexts corresponded to increased activation in cortical regions previously shown to respond to social conflict in proportion to subsequent conformity (Campbell-Meiklejohn et al., 2010). The tendency to self-monitor predicted a selectively enhanced response to accordance with others in the right temporoparietal junction (rTPJ). The findings anatomically decompose vmPFC value representations according to computational requirements and provide biological insight into the social transmission of preference and reassurance gained from the confidence of others. Significance Statement: Decades of research have provided evidence that the ventromedial prefrontal cortex (vmPFC) signals the satisfaction we expect from imminent actions. However, we have a surprisingly modest understanding of the organization of value across this substantial and varied region. This study finds that using cues of the reliability of other peoples'; knowledge to enhance expectation of personal success generates value correlates that are anatomically distinct from those concurrently computed from direct, personal experience. This suggests that representation of decision values in vmPFC is suborganized according to the underlying computation, consistent with what we know about the anatomical heterogeneity of the region. These results also provide insight into the observational learning process by which someone else's confidence can sway and reassure our choices

Enhanced automatic action imitation and intact imitation- inhibition in schizophrenia

Imitation plays a key role in social learning and in facilitating social interactions and likely constitutes a basic building block of social cognition that supports higher-level social abilities. Recent findings suggest that patients with schizophrenia have imitation impairments that could contribute to the social impairments associated with the disorder. However, extant studies have specifically assessed voluntary imitation or automatic imitation of emotional stimuli without controlling for potential confounders. The imitation impairments seen might therefore be secondary to other cognitive, motoric or emotional deficits associated with the disorder. To overcome this issue, we used an automatic imitation paradigm with nonemotional stimuli to assess automatic imitation and the top-down modulation of imitation where participants were required to lift one of two fingers according to a number shown on the screen whilst observing the same or the other finger movement. In addition, we used a control task with a visual cue in place of a moving finger, to isolate the effect of observing finger movement from other visual cueing effects. Data from 33 patients (31 medicated) and 40 matched healthy controls were analyzed. Patients displayed enhanced imitation and intact top-down modulation of imitation. The enhanced imitation seen in patients may have been medication induced as larger effects were seen in patients receiving higher antipsychotic doses. In sum, we did not find an imitation impairment in schizophrenia. The results suggest that previous findings of impaired imitation in schizophrenia might have been due to other cognitive, motoric and/or emotional deficits