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Abstract Background Technological burden and medical complexity are significant drivers of clinician burnout. Electronic health record(EHR)-based population health management tools can be used to identify high-risk patient populations and implement prophylactic health practices. Their impact on clinician burnout, however, is not well understood. Our objective was to assess the relationship between ratings of EHR-based population health management tools and clinician burnout. Methods We conducted cross-sectional analyses of 2018 national Veterans Health Administration(VA) primary care personnel survey, administered as an online survey to all VA primary care personnel (n = 4257, response rate = 17.7%), using bivariate and multivariate logistic regressions. Our analytical sample included providers (medical doctors, nurse practitioners, physicians’ assistants) and nurses (registered nurses, licensed practical nurses). The outcomes included two items measuring high burnout. Primary predictors included importance ratings of 10 population health management tools (eg. VA risk prediction algorithm, recent hospitalizations and emergency department visits, etc.). Results High ratings of 9 tools were associated with lower odds of high burnout, independent of covariates including VA tenure, team role, gender, ethnicity, staffing, and training. For example, clinicians who rated the risk prediction algorithm as important were less likely to report high burnout levels than those who did not use or did not know about the tool (OR 0.73; CI 0.61-0.87), and they were less likely to report frequent burnout (once per week or more) (OR 0.71; CI 0.60-0.84). Conclusions Burned-out clinicians may not consider the EHR-based tools important and may not be using them to perform care management. Tools that create additional technological burden may need adaptation to become more accessible, more intuitive, and less burdensome to use. Finding ways to improve the use of tools that streamline the work of population health management and/or result in less workload due to patients with poorly managed chronic conditions may alleviate burnout. More research is needed to understand the causal directional of the association between burnout and ratings of population health management tools.

Abstract Background Organized physical activity programs have been shown to provide wide benefits to participants, though there are relatively few studies examining the impact of these programs for individuals with developmental disabilities. This pilot study was conducted to determine the feasibility and impact of an undergraduate-led dance intervention program for children and adolescents with developmental disabilities. We evaluated the impact of the dance program on motor ability and social skills. Methods The study design was a waitlist control clinical trial in which participants were randomized to active and control groups. Eligible participants included male and female children and adolescents between the ages of 4 and 17 years with neurodevelopmental disabilities. The Motor Assessment Battery for Children Checklist and the Social Responsiveness Scale were used to assess change in motor and social skills, respectively. After gathering baseline data, the active group completed 1 h of online dance classes per week for 10 weeks, while the control group entered a 10-week waiting period. All participants then returned for a follow-up visit. Pre- and post-intervention data were analyzed using linear mixed-effects modeling adjusting for age and class attendance with subject random intercept. Results We recruited and randomized 43 participants with neurodevelopmental disabilities (mean age = 8.63, SD = 2.98), of which 30 participated in dance classes. The attendance rate was 82.6% for the active group and 61.7% for the control group. The active group demonstrated a significant improvement in motor skills in an unpredictable environment, as indicated on the Motor Assessment Battery for Children Checklist (n = 21, p = 0.05). We also observed positive trends in social skills that did not reach significance. Conclusions Our results indicate that it is feasible to develop and implement a fully digital dance intervention program for individuals with developmental disabilities. Further, we find that change in motor skills can be detected after just 10 h of low-intensity participation. However, a lack of significant change in social skills coupled with limitations in study implementation suggests further research is needed to determine the full impact of this dance program. Trial Registration ClinicalTrials.gov Protocol Registration System: Protocol ID 20-001680-AM-00005, registered 17/2/2021 – Retrospectively Registered, https://clinicaltrials.gov/study/NCT04762290 .

The SMART Pass filter (Boston Scientific) aims to reduce inappropriate shocks (IASs) from subcutaneous implantable cardioverter-defibrillators by filtering out low-frequency signals such as T waves. However, this filter is deactivated in the presence of diminished R-wave sensing. We describe a case of IAS in the setting of extensive intra-abdominal hemorrhage.

Background: General anaesthesia (GA) for atrial fibrillation (AF) ablation is often preferred over conscious sedation (CS) to minimize patient discomfort and reduce the risk of map disruption from patient movement but may pose an additional risk to some patients with significant comorbidity or poor cardiac function. Methods: We extracted data for 300 patients who underwent AF ablation between the years 2017 and 2019 and compared the outcomes of AF ablation with CS and GA. Results: Compared to the GA group, patients were younger in the CS group (63 versus 66 years, p = 0.02), had less persistent AF (34% versus 46%, p = 0.048) and the left atrial dimension was smaller (41 versus 45 mm, p = 0.01). More patients had cryoballoon ablation (CBA) than radiofrequency (RFA) ablation in the CS than the GA group (88% CB with CS and 56% RF with GA, p

IntroductionMeasuring long-term housing outcomes is important for evaluating the impacts of services for individuals with homeless experience. However, assessing long-term housing status using traditional methods is challenging. The Veterans Affairs (VA) Electronic Health Record (EHR) provides detailed data for a large population of patients with homeless experiences and contains several indicators of housing instability, including structured data elements (e.g., diagnosis codes) and free-text clinical narratives. However, the validity of each of these data elements for measuring housing stability over time is not well-studied.MethodsWe compared VA EHR indicators of housing instability, including information extracted from clinical notes using natural language processing (NLP), with patient-reported housing outcomes in a cohort of homeless-experienced Veterans.ResultsNLP achieved higher sensitivity and specificity than standard diagnosis codes for detecting episodes of unstable housing. Other structured data elements in the VA EHR showed promising performance, particularly when combined with NLP.DiscussionEvaluation efforts and research studies assessing longitudinal housing outcomes should incorporate multiple data sources of documentation to achieve optimal performance.

In value-based decision making, options are selected according to subjective values assigned by the individual to available goods and actions. Despite the importance of this faculty of the mind, the neural mechanisms of value assignments, and how choices are directed by them, remain obscure. To investigate this problem, we used a classic measure of utility maximization, the Generalized Axiom of Revealed Preference, to quantify internal consistency of food preferences in Caenorhabditis elegans, a nematode worm with a nervous system of only 302 neurons. Using a novel combination of microfluidics and electrophysiology, we found that C. elegans food choices fulfill the necessary and sufficient conditions for utility maximization, indicating that nematodes behave as if they maintain, and attempt to maximize, an underlying representation of subjective value. Food choices are well-fit by a utility function widely used to model human consumers. Moreover, as in many other animals, subjective values in C. elegans are learned, a process we find requires intact dopamine signaling. Differential responses of identified chemosensory neurons to foods with distinct growth potentials are amplified by prior consumption of these foods, suggesting that these neurons may be part of a value-assignment system. The demonstration of utility maximization in an organism with a very small nervous system sets a new lower bound on the computational requirements for utility maximization and offers the prospect of an essentially complete explanation of value-based decision making at single neuron resolution in this organism.

In this intervention article, we cultivate an anti-colonial critique of the ideational genealogy and conceptual materialisation of the social licence to operate (SLO) in the extractive industries in order to open a conversation about the racialised and colonial logics underlying its enactment and discursive practices. SLO functions to restrict the emergence of imaginary political potentials within communities impacted by extractive projects. We focus on the role of academics and social science researchers within and beyond the space of the university in engineering, shaping, and promoting dominant SLO frameworks, and endorsing the power and mythology of SLO. We do so in conversation with decolonial orientations that simultaneously analyse the colonial logics within corporate practice and galvanise epistemic justice beyond colonial and epistemic extractivism. The university, as a site for the refinement and promotion of hegemonic concepts like SLO, is an important space for post-extractive struggles.

Abstract Background High-cost high-need patients are typically defined by risk or cost thresholds which aggregate clinically diverse subgroups into a single ‘high-need high-cost’ designation. Programs have had limited success in reducing utilization or improving quality of care for high-cost high-need Medicaid patients, which may be due to the underlying clinical heterogeneity of patients meeting high-cost high-need designations. Methods Our objective was to segment a population of high-cost high-need Medicaid patients (N = 676,161) eligible for a national complex case management program between January 2012 and May 2015 to disaggregate clinically diverse subgroups. Patients were eligible if they were in the top 5 % of annual spending among UnitedHealthcare Medicaid beneficiaries. We used k-means cluster analysis, identified clusters using an information-theoretic approach, and named clusters using the patients’ pattern of acute and chronic conditions. We assessed one-year overall and preventable hospitalizations, overall and preventable emergency department (ED) visits, and cluster stability. Results Six clusters were identified which varied by utilization and stability. The characteristic condition patterns were: 1) pregnancy complications, 2) behavioral health, 3) relatively few conditions, 4) cardio-metabolic disease, and complex illness with relatively 5) low or 6) high resource use. The patients varied by cluster by average ED visits (2.3–11.3), hospitalizations (0.3–2.0), and cluster stability (32–91%). Conclusions We concluded that disaggregating subgroups of high-cost high-need patients in a large multi-state Medicaid sample identified clinically distinct clusters of patients who may have unique clinical needs. Segmenting previously identified high-cost high-need populations thus may be a necessary strategy to improve the effectiveness of complex case management programs in Medicaid.

Abstract Vaccination of the global population against COVID-19 is a great scientific, logistical, and moral challenge. Despite the rapid development and authorization of several full-length Spike (S) protein vaccines, the global demand outweighs the current supply and there is a need for safe, potent, high-volume, affordable vaccines that can fill this gap, especially in low- and middle-income countries. Whether SARS-CoV-2 S-protein receptor-binding domain (RBD)-based vaccines could fill this gap has been debated, especially with regards to its suitability to protect against emerging viral variants of concern. Given a predominance for elicitation of neutralizing antibodies (nAbs) that target RBD following natural infection or vaccination, a key biomarker of protection, there is merit for selection of RBD as a sole vaccine immunogen. With its high-yielding production and manufacturing potential, RBD-based vaccines offer an abundance of temperature-stable doses at an affordable cost. In addition, as the RBD preferentially focuses the immune response to potent and recently recognized cross-protective determinants, this domain may be central to the development of future pan-sarbecovirus vaccines. In this study, we review the data supporting the non-inferiority of RBD as a vaccine immunogen compared to full-length S-protein vaccines with respect to humoral and cellular immune responses against both the prototype pandemic SARS-CoV-2 isolate and emerging variants of concern.

Background Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is now the standard of care, but whether the demonstrated benefits of RM translate into improvements in heart failure (HF) management is controversial. This systematic review addresses the role of RM in patients with HF with a CIED.Methods and results A systematic search of the literature for randomised clinical trials in patients with HF and a CIED assessing efficacy/effectiveness of RM was performed using MEDLINE, PubMed and Embase. Meta-analysis was performed on the effects of RM of CIEDs in patients with HF on mortality and readmissions. Effects on implantable cardiac defibrillator (ICD) therapy, healthcare costs and clinic presentations were also assessed.607 articles were identified and refined to 10 studies with a total of 6579 patients. Implementation of RM was not uniform with substantial variation in methodology across the studies. There was no reduction in mortality or hospital readmission rates, while ICD therapy findings were inconsistent. There was a reduction in patient-associated healthcare costs and reduction in healthcare presentations.Conclusion RM for patients with CIEDs and HF was not uniformly performed. As currently implemented, RM does not provide a benefit on overall mortality or the key metric of HF readmission. It does provide a reduction in healthcare costs and healthcare presentations.PROSPERO REGISTRATION NUMBER CRD42019129270.

Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ∼4 months of age, both male and female Zmpste24−/− mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24–knockout mice. To boost farnesyl–prelamin A levels, we bred in the “prelamin A–only” Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl–prelamin A, reduces adipose tissue stores, but only modestly and only in male mice.

How COVID-19 vaccine is distributed within low- and middle-income countries has received little attention outside of equity or logistical concerns but may ultimately affect campaign impact in terms of infections, severe cases, or deaths averted. In this study we examined whether subnational (urban-rural) prioritization may affect the cumulative two-year impact on disease transmission and burden of a vaccination campaign using an agent-based model of COVID-19 in a representative COVID-19 Vaccines Global Access (COVAX) Advanced Market Commitment (AMC) setting. We simulated a range of vaccination strategies that differed by urban-rural prioritization, age group prioritization, timing of introduction, and final coverage level. Urban prioritization averted more infections in only a narrow set of scenarios, when internal migration rates were low and vaccination was started by day 30 of an outbreak. Rural prioritization was the optimal strategy for all other scenarios, e.g., with higher internal migration rates or later start dates, due to the presence of a large immunological naive rural population. Among other factors, timing of the vaccination campaign was important to determining maximum impact, and delays as short as 30 days prevented larger campaigns from having the same impact as smaller campaigns that began earlier. The optimal age group for prioritization depended on choice of metric, as prioritizing older adults consistently averted more deaths across all of the scenarios. While guidelines exist for these latter factors, urban-rural allocation is an orthogonal factor that we predict to affect impact and warrants consideration as countries plan the scale-up of their vaccination campaigns.

Introduction Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. Direct current cardioversion is commonly used to restore sinus rhythm in patients with AF. Chest pressure may improve cardioversion success through decreasing transthoracic impedance and increasing cardiac energy delivery. We aim to assess the efficacy and safety of routine chest pressure with direct current cardioversion for AF.Methods and analysis Multicentre, double blind (patient and outcome assessment), randomised clinical trial based in New South Wales, Australia. Patients will be randomised 1:1 to control and interventional arms. The control group will receive four sequential biphasic shocks of 150 J, 200 J, 360 J and 360 J with chest pressure on the last shock, until cardioversion success. The intervention group will receive the same shocks with chest pressure from the first defibrillation. Pads will be placed in an anteroposterior position. Success of cardioversion will be defined as sinus rhythm at 1 min after shock. The primary outcome will be total energy provided. Secondary outcomes will be success of first shock to achieve cardioversion, transthoracic impedance and sinus rhythm at post cardioversion ECG.Ethics and dissemination Ethics approval has been confirmed at all participating sites via the Research Ethics Governance Information System. The trial has been registered on the Australia New Zealand Clinical Trials Registry (ACTRN12620001028998). De-identified patient level data will be available to reputable researchers who provide sound analysis proposals.

Two large pivotal phase III studies demonstrated the efficacy of the tetravalent dengue vaccine (CYD-TDV; Dengvaxia®, Sanofi Pasteur) against all dengue serotypes. Here we present an unprecedented integrated summary of the immunogenicity of CYD-TDV to identify the parameters driving the neutralizing humoral immune response and evolution over time. We summarized the immunogenicity profiles of a 3-dose schedule of CYD-TDV administered 6 months apart across 10 phase II and 6 phase III trials undertaken in dengue endemic and non-endemic countries. Dengue neutralizing antibody titers in sera were determined at centralized laboratories using the 50% plaque reduction neutralization test (PRNT50) at baseline, 28 d after the third dose, and annually thereafter for up to 4 y after the third dose in some studies. CYD-TDV elicits neutralizing antibody responses against all 4 dengue serotypes; geometric mean titers (GMTs) increased from baseline to post-dose 3. GMTs were influenced by several parameters including age, baseline dengue seropositivity and region. In the 2 pivotal studies, GMTs decreased initially during the first 2 y post-dose 3 but appear to stabilize or slightly increase again in the third year. GMTs persisted 1.2–3.2-fold higher than baseline levels for up to 4 y post-dose 3 in other studies undertaken in dengue endemic countries. Our integrated analysis captures the fullness of the CYD-TDV immunogenicity profile across studies, age groups and regions; by presenting the available data in this way general trends and substantial outliers within each grouping can be easily identified. CYD-TDV elicits neutralizing antibody responses against all dengue serotypes, with differences by age and endemicity, which persist above baseline levels in endemic countries.

Introduction: Dengue is an important and still growing public health problem associated with substantial morbidity, as well as significant social and economic impact. The present review describes the main features and development of the first dengue vaccine (CYD-TDV, Dengvaxia®), which has been licensed by several dengue-endemic countries in Asia and Latin America for use in populations above 9 years of age. Areas covered: The review focuses on the large clinical development of CYD-TDV, which includes in particular two pivotal phase III efficacy trials conducted in Asia and Latin America and supported vaccine licensure. Based on these clinical data, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended considering introduction of the vaccine in geographic settings (national or subnational) with high burden of disease. Long-term safety follow-up studies of the efficacy trials are currently ongoing, and post-licensure studies will evaluate the vaccine effectiveness and safety in ‘real-life’ following vaccine introduction. Expert commentary: During vaccine development, a number of complexities were tackled, innovation pursued, and risk managed. These aspects, as well as the potential impact of CYD-TDV on public health are also discussed.

Purpose: To compare the rates of rapid posterior capsule opacification (PCO) formation in the first 3 months following femtosecond laser-assisted cataract surgery (FLACS) to manual anterior capsulorhexis. Methods: Retrospective review of 29 cases of FLACS, comparing the rates of PCO in the first 3 months following surgery to 50 consecutive cases of manual anterior capsulorhexis. Results: Seven of the 29 FLACS cases developed PCO requiring capsulotomy at 3 months, while none of the control cases required a capsulotomy over the same time period (p < 0.05). Conclusion: There is an increased incidence of early-onset PCO following the use of femtosecond laser in cataract surgery that is otherwise unfounded in manual capsulorhexis. This suggests that the use of a femtosecond laser could increase the risk of this novel postoperative complication.

(1) Background: Internal medicine (IM) resident physicians need to be trained to care for older adults and transition them safely across care settings. Objective: The study purpose was to evaluate the efficacy of a curriculum in geriatrics assessment and communication skills for transitions of care (TOCs) to IM resident physicians. (2) Methods: IM residents rotated for 4 weeks on the geriatrics consult service at a large public teaching hospital, where they received didactic lectures and clinical experience in consultation and transitional care. The curriculum was designed to meet consensus guidelines for minimum geriatrics competencies expected of IM residents. Previously validated and published assessment tools were used for geriatrics knowledge and attitudes. Locally developed tools were used to directly observe and rate communication skills, and self-assess geriatrics assessment and health literacy skills. The curriculum was evaluated using a quasi-experimental, nonrandomized, single-group pre- and post-test observational design. Data on 31 subjects were collected over 18 months and analyzed using mixed-effects models. (3) Results: Average knowledge scores improved from 65% to 74% (Δ9%, 95% CI 4–13%, p < 0.001). Communication skills improved by an average of 1.15 points (95% CI 0.66–1.64, p < 0.001) on a 9-point scale. Attitudes did not change significantly. Self-rated confidence in geriatrics assessment and health literacy skills improved modestly. (4) Conclusions: The curriculum is effective in teaching basic geriatrics knowledge and communication skills, and increasing self-confidence in geriatrics assessment skills. In settings where an inpatient geriatrics consult service is feasible, the curriculum may be a model for combining geriatrics and TOC training.

A safe and effective vaccine against RSV remains an important unmet public health need. Intranasally (IN) delivered live-attenuated vaccines represent the most extensively studied approach for immunization of RSV-naïve infants and children, however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we report pre-clinical immunogenicity and efficacy data utilizing a live-attenuated vaccine candidate, RGΔM2-2, which was obtained by deleting the M2-2 open reading frame from the genome of the MSA1 clinical isolate. Intramuscular (IM) administration of RGΔM2-2 in cotton rats induced immunity and protective efficacy that was comparable to that induced by intranasal (IN) immunization. In contrast, the protective efficacy of RGΔM2-2 delivered by the IM route to African green monkeys was substantially reduced as compared to the efficacy following IN administration, despite comparable levels of serum neutralizing antibodies. This result suggests that mucosal immunity may play an important role in RSV protection. The RGΔM2-2 vaccine also demonstrated different attenuation profiles when tested in cotton rats, non-human primates, and a human airway epithelial (HAE) cell model. The data suggest RGΔM2-2 is less attenuated than a similarly designed vaccine candidate constructed on the A2 genetic background. These findings have important implications with regard to both the design and the preclinical safety testing of live-attenuated vaccines.

BackgroundSurgical patients aged 65 and over face a higher risk of cardiac complications from noncardiac surgery. The Revised Cardiac Risk Index (RCRI) and the Gupta Myocardial Infarction or Cardiac Arrest (MICA) calculator are widely used to predict this risk, but they are not specifically designed to predict MICA in geriatric patients. Our hypothesis is that a new geriatric‐sensitive index, derived from geriatric data, will capture this population's unique response to risk factors. Methods and ResultsThe model was developed using the NSQIP (National Surgical Quality Improvement Program) 2013 geriatric cohort (N=584,931) (210,914 age ≥65) and validated on the NSQIP 2012 geriatric cohort (N= 485,426) (172,905 age ≥65). Least Angle Shrinkage and Selection Operator regression was used for initial variable selection. The Geriatric‐Sensitive Cardiac Risk Index (GSCRI) was then evaluated in the 2012 data set. The area under the curve (AUC) was compared among the GSCRI, RCRI, and Gupta MICA in the 2012 data set. The GSCRI had an AUC of 0.76 in the validation cohort among geriatric patients. When the Gupta MICA was tested on geriatric patients in the validation cohort, a significant deterioration (≈17%) was noted, as well as a significant underestimation of the risk. The GSCRI AUC of 0.76 in the geriatric subset was significantly greater (P

This study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of the tetravalent dengue vaccine, CYD-TDV, and thereby enabled virus genotype-specific estimates of vaccine efficacy (VE). Envelope gene sequences (n = 661) from 11 DENV genotypes in 10 endemic countries provided a contemporaneous global snapshot of DENV population genetics and revealed high amino acid identity between the E genes of vaccine strains and wild-type viruses from trial participants, including at epitope sites targeted by virus neutralising human monoclonal antibodies. Post-hoc analysis of all CYD14/15 trial participants revealed a statistically significant genotype-level VE association within DENV-4, where efficacy was lowest against genotype I. In subgroup analysis of trial participants age 9–16 years, VE estimates appeared more balanced within each serotype, suggesting that genotype-level heterogeneity may be limited in older children. Post-licensure surveillance is needed to monitor vaccine performance against the backdrop of DENV sequence diversity and evolution.

We determined the activation volumes (V*) for polycrystalline magnesite with grain sizes of 2 and 80 µm deforming by low temperature plasticity (LTP) mechanisms (kinking and dislocation glide), diffusion creep, and dislocation creep at temperatures of 500, 750, and 900 °C, respectively, and a strain rate of 1−2 × 10−5 s−1 at effective pressures of 2.9−7.5 GPa in a D-DIA and 0.76 GPa in a Griggs apparatus. In each set of experiments performed at a given temperature, the strength of magnesite increases with increasing pressure. Microstructures of fine-grained magnesite deformed at 500 °C and 750 °C are consistent with deformation by LTP mechanisms and diffusion creep, respectively. Microstructures of coarse-grained magnesite deformed at 900 °C are consistent with deformation by dislocation creep. Pressure dependencies of magnesite flow laws for LTP, diffusion creep, and dislocation creep are given by activation volumes of 34 (± 7), 2 (± 1), and 10 (± 5) × 10−6 m3/mol, respectively. Addition of these activation volumes to previously determined flow laws predicts magnesite strength to be much lower than the flow strength of olivine at all subduction zone depths of the upper mantle. Thus, subducting oceanic lithosphere that has been partially carbonated by reaction with CO2-bearing fluids may deform at lowered stresses where magnesite is present, possibly resulting in strain localization and unstable run-away shear.

BACKGROUND:Two large-scale efficacy studies with the recombinant yellow fever-17D-dengue virus, live-attenuated, tetravalent dengue vaccine (CYD-TDV) candidate undertaken in Asia (NCT01373281) and Latin America (NCT01374516) demonstrated significant protection against dengue disease during two years' active surveillance (active phase). Long-term follow up of participants for breakthrough disease leading to hospitalization is currently ongoing (hospital phase). METHODOLOGY/PRINCIPAL FINDINGS:We assessed the cytokine profile in acute sera from selected participants hospitalized (including during the active phase) up to the beginning of the second year of long-term follow up for both studies. The serum concentrations of 38 cytokines were measured in duplicate using the Milliplex Human Cytokine MAGNETIC BEAD Premixed 38 Plex commercial kit (Millipore, Billerica, MA, USA). Partial least squares discriminant analyses did not reveal any difference in the overall cytokine profile of CYD-TDV and placebo recipients hospitalized for breakthrough dengue regardless of stratification used. In addition, there was no difference in the cytokine profile for breakthrough dengue among those aged

The increasing professionalism of sports persons and desire of consumers to imitate this has led to an increased metrification of sport. This has been driven in no small part by the widespread availability of comparatively cheap assessment technologies and, more recently, wearable technologies. Historically, whilst these have produced large data sets, often only the most rudimentary analysis has taken place (Wisbey et al in: “Quantifying movement demands of AFL football using GPS tracking”). This paucity of analysis is due in no small part to the challenges of analysing large sets of data that are often from disparate data sources to glean useful key performance indicators, which has been a largely a labour intensive process. This paper presents a framework that can be cloud based for the gathering, storing and algorithmic interpretation of large and inhomogeneous time series data sets. The framework is architecture based and technology agnostic in the data sources it can gather, and presents a model for multi set analysis for inter- and intra- devices and individual subject matter. A sample implementation demonstrates the utility of the framework for sports performance data collected from distributed inertial sensors in the sport of swimming.

The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate (NO3-¬) and production of the potent greenhouse gas, nitrous oxide (N2O). A number of factors are known to control these processes, including O2 concentrations and moisture content, N, C, pH and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub cm areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location and potential for N2O production from soils.