Age groups and spread of influenza: implications for vaccination strategy

<p>Abstract</p> <p>Background</p> <p>The unpredictable nature of the potentially devastating impact of 2009 pH1N1 influenza pandemic highlights the need for pandemic preparedness planning, where modeling studies could be most useful for simulations of possible future scenarios.</p> <p>Methods</p> <p>A compartmental model with pre-symptomatic and asymptomatic influenza infections is proposed which incorporates age groups as well as intervention measures such as age-specific vaccination, in order to study spread of influenza in a community.</p> <p>Results</p> <p>We derive the basic reproduction number and other effective reproduction numbers under various intervention measures. For illustration, we make use of the Pneumonia and Influenza (P&I) mortality data and vaccination data of the very young (age 0-2) and the very old (age >64) during 2004-2005 Taiwan winter influenza season to fit our model and to compute the relevant reproduction numbers. The reproduction number for this winter flu season is estimated to be slightly above one (~1.0001).</p> <p>Conclusions</p> <p>Comparatively large errors in fitting the P&I mortality data of the elderly (>64) were observed shortly after winter school closings in January, which may indicate the impact of younger, more active age groups transmitting influenza to other age groups outside of the school settings; in particular, to the elderly in the households. Pre-symptomatic infections seemed to have little effect on the model fit, while asymptomatic infection by asymptomatic infectives has a more pronounced impact on the model fit for the elderly mortality, perhaps indicating a larger role in disease transmission by asymptomatic infection. Simulations indicate that the impact of vaccination on the disease incidence might not be fully revealed in the change (or the lack thereof) in the effective reproduction number with interventions, but could still be substantial. The estimated per contact transmission probability for susceptible elderly is significantly higher than that of any other age group, perhaps highlighting the vulnerability of the elderly due to close contacts with their caretakers from other age groups. The relative impact of targeting the very young and the very old for vaccination was weakened by their relative inactivity, thus giving evidence of the lack of impact of vaccinating these two groups on the overall transmissibility of the disease in the community. This further underscores the need for morbidity-based strategy to prevent elderly mortality.</p

A Model for the Interplay of Receptor Recycling and Receptor-Mediated Contact in T Cells

Orientation of organelles inside T cells (TC) toward antigen-presenting cells (APC) ensures that the immune response is properly directed, but the orientation mechanisms remain largely unknown. Structural dynamics of TC are coupled to dynamics of T-cell receptor (TCR), which recognizes antigen on the APC surface. Engagement of the TCR triggers its internalization followed by delayed polarized recycling to the plasma membrane through the submembrane recycling compartment (RC), which organelle shares intracellular location with the TC effector apparatus. TCR engagement also triggers TC-APC interface expansion enabling further receptor engagement. To analyze the interplay of the cell-cell contact and receptor dynamics, we constructed a new numerical model. The new model displays the experimentally observed selective stabilization of the contact initiated next to the RC, and only transient formation of contact diametrically opposed to the RC. In the general case wherein the TC-APC contact is initiated in an arbitrary orientation to the RC, the modeling predicts that the contact dynamics and receptor recycling can interact, resulting effectively in migration of the contact to the TC surface domain adjacent to the submembrane RC. Using three-dimensional live-cell confocal microscopy, we obtain data consistent with this unexpected behavior. We conclude that a TC can stabilize its contact with an APC by aligning it with the polarized intracellular traffic of TCR. The results also suggest that the orientation of TC organelles, such as the RC and the effector apparatus, toward the APC can be achieved without any intracellular translocation of the organelles

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Serum 25-Hydroxyvitamin D and the Incidence of Acute Viral Respiratory Tract Infections in Healthy Adults

Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections.In this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009-2010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill.Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese

Can Interactions between Timing of Vaccine-Altered Influenza Pandemic Waves and Seasonality in Influenza Complications Lead to More Severe Outcomes?

Vaccination can delay the peak of a pandemic influenza wave by reducing the number of individuals initially susceptible to influenza infection. Emerging evidence indicates that susceptibility to severe secondary bacterial infections following a primary influenza infection may vary seasonally, with peak susceptibility occurring in winter. Taken together, these two observations suggest that vaccinating to prevent a fall pandemic wave might delay it long enough to inadvertently increase influenza infections in winter, when primary influenza infection is more likely to cause severe outcomes. This could potentially cause a net increase in severe outcomes. Most pandemic models implicitly assume that the probability of severe outcomes does not vary seasonally and hence cannot capture this effect. Here we show that the probability of intensive care unit (ICU) admission per influenza infection in the 2009 H1N1 pandemic followed a seasonal pattern. We combine this with an influenza transmission model to investigate conditions under which a vaccination program could inadvertently shift influenza susceptibility to months where the risk of ICU admission due to influenza is higher. We find that vaccination in advance of a fall pandemic wave can actually increase the number of ICU admissions in situations where antigenic drift is sufficiently rapid or where importation of a cross-reactive strain is possible. Moreover, this effect is stronger for vaccination programs that prevent more primary influenza infections. Sensitivity analysis indicates several mechanisms that may cause this effect. We also find that the predicted number of ICU admissions changes dramatically depending on whether the probability of ICU admission varies seasonally, or whether it is held constant. These results suggest that pandemic planning should explore the potential interactions between seasonally varying susceptibility to severe influenza outcomes and the timing of vaccine-altered pandemic influenza waves

The abilities of improved schizophrenia patients to work and live independently in the community: a 10-year long-term outcome study from Mumbai, India

Background: The outcome of schizophrenia has several determinants. Socioecological factors, particularly living conditions, migration, community and culture, not only affect the level of risk but also the outcome. Mega cities around the world show a unique socioecological condition that has several challenges for mental health. The present study reports on the long-term status of patients with schizophrenia in such a mega city: Mumbai, India. Aim This study aims to reveal the long-term outcome of patients suffering from schizophrenia with special reference to clinical symptoms and social functioning. Methods: The cohort for this study was drawn from a 10-year follow-up of first episode schizophrenia. Patients having completed 10 years of consistent treatment after first hospitalisation were assessed on psychopathological and recovery criteria. Clinical as well as social parameters of recovery were evaluated. Descriptive statistics with 95% confidence intervals are provided. Results: Of 200 patients recruited at the beginning of this study, 122 patients (61%) were present in the city of Mumbai at the end of 10-year follow-up study period. Among 122 available patients, 101 patients (50.5%) were included in the assessment at the end of 10-year follow-up study period, 6 patients (3.0%) were excluded from the study due to changed diagnosis, and 15 patients (7.5%) were excluded due to admission into long-term care facilities. This indicates that 107 out of 122 available patients (87.7%) were living in the community with their families. Out of 101 (50.5%) patients assessed at the end of 10 years, 61 patients (30.5%) showed improved recovery on the Clinical Global Impression Scale, 40 patients (20%) revealed no improvement in the recovery, 43 patients (72.9%) were able to live independently, and 24 patients (40%) were able to find employment. Conclusions: With 10 years of treatment, the recovery rate among schizophrenia patients in Mumbai was 30.5%. Among the patients, 87.7% of patients lived in the community, 72.9% of patients lived independently, and 40% of patients obtained employment. However, 60% of patients were unable to return to work, which highlights the need for continued monitoring and support to prevent the deterioration of health in these patients. It is likely that socioecological factors have played a role in this outcome

Mindful "Vitality in Practice": an intervention to improve the work engagement and energy balance among workers; the development and design of the randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Modern working life has become more mental and less physical in nature, contributing to impaired mental health and a disturbed energy balance. This may result in mental health problems and overweight. Both are significant threats to the health of workers and thus also a financial burden for society, including employers. Targeting work engagement and energy balance could prevent impaired mental health and overweight, respectively.</p> <p>Methods/Design</p> <p>The study population consists of highly educated workers in two Dutch research institutes. The intervention was systematically developed, based on the Intervention Mapping (IM) protocol, involving workers and management in the process. The workers' needs were assessed by combining the results of interviews, focus group discussions and a questionnaire with available literature. Suitable methods and strategies were selected resulting in an intervention including: eight weeks of customized mindfulness training, followed by eight sessions of e-coaching and supporting elements, such as providing fruit and snack vegetables at the workplace, lunch walking routes, and a buddy system. The effects of the intervention will be evaluated in a RCT, with measurements at baseline, six months (T1) and 12 months (T2). In addition, cost-effectiveness and process of the intervention will also be evaluated.</p> <p>Discussion</p> <p>At baseline the level of work engagement of the sample was "average". Of the study population, 60.1% did not engage in vigorous physical activity at all. An average working day consists of eight sedentary hours. For the Phase II RCT, there were no significant differences between the intervention and the control group at baseline, except for vigorous physical activity. The baseline characteristics of the study population were congruent with the results of the needs assessment. The IM protocol used for the systematic development of the intervention produced an appropriate intervention to test in the planned RCT.</p> <p>Trial registration number</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2199">NTR2199</a></p