To test or to treat? an analysis of influenza testing and Antiviral treatment strategies using economic computer modeling

Background: Due to the unpredictable burden of pandemic influenza, the best strategy to manage testing, such as rapid or polymerase chain reaction (PCR), and antiviral medications for patients who present with influenza-like illness (ILI) is unknown. Methodology/Principal Findings: We developed a set of computer simulation models to evaluate the potential economic value of seven strategies under seasonal and pandemic influenza conditions: (1) using clinical judgment alone to guide antiviral use, (2) using PCR to determine whether to initiate antivirals, (3) using a rapid (point-of-care) test to determine antiviral use, (4) using a combination of a point-of-care test and clinical judgment, (5) using clinical judgment and confirming the diagnosis with PCR testing, (6) treating all with antivirals, and (7) not treating anyone with antivirals. For healthy younger adults (<65 years old) presenting with ILI in a seasonal influenza scenario, strategies were only cost-effective from the societal perspective. Clinical judgment, followed by PCR and point-of-care testing, was found to be cost-effective given a high influenza probability. Doubling hospitalization risk and mortality (representing either higher risk individuals or more virulent strains) made using clinical judgment to guide antiviral decision-making cost-effective, as well as PCR testing, point-of-care testing, and point-of-care testing used in conjunction with clinical judgment. For older adults (≥65 years old), in both seasonal and pandemic influenza scenarios, employing PCR was the most cost-effective option, with the closest competitor being clinical judgment (when judgment accuracy ≥50%). Point-of-care testing plus clinical judgment was cost-effective with higher probabilities of influenza. Treating all symptomatic ILI patients with antivirals was cost-effective only in older adults. Conclusions/Significance: Our study delineated the conditions under which different testing and antiviral strategies may be cost-effective, showing the importance of accuracy, as seen with PCR or highly sensitive clinical judgment. © 2010 Lee et al

The mutual benefit of patient and public involvement in research: an example from a feasibility study (MoTaStim-Foot)

Patient and public involvement (PPI) in research has increased steadily over the last two decades and is now both expected and appropriately resourced by many funding bodies, including the National Institute for Health Research (NIHR). However, PPI in research occurs in many different capacities and numerous frameworks exist for reporting or appraising patient involvement activities. The aim of this article is to describe processes involving PPI contributions to an NIHR-funded mixed-methods feasibility study (MoTaStim-Foot). Details of PPI advisors’ input, from initial identification and prioritisation of research ideas, to research delivery and dissemination, are discussed

Lab-based X-ray micro-computed tomography coupled with machine-learning segmentation to investigate phosphoric acid leaching in high-temperature polymer electrolyte fuel cells

A machine-learning approach is used to segment 14 X-ray computed-tomography datasets acquired by lab-based scanning of laser-milled, high-temperature polymer electrolyte fuel cell samples mounted in a 3D-printed sample holder. Two modes of operation, one with constant current load and the other with current cycling, are explored and their impact on microstructural change is correlated with electrochemical performance degradation. Constant-current testing shows the overall quantity of phosphoric acid in the gas diffusion layers is effectively unchanged between 50 and 100 h of operation but that inter-electrode distribution becomes less uniform. Current-cycling tests reveal similar quantities of phosphoric acid but a different intra-electrode distribution. Membrane swelling appears more pronounced after current-cycling tests and in both cases, significant catalyst layer migration is observed. The present analysis provides a lab-based approach to monitoring microstructural degradation in high-temperature polymer electrolyte fuel cells and provides a more accessible and more statistically robust platform for assessing the impact of phosphoric acid mitigation strategies

Risk factors for race-day fatality in flat racing Thoroughbreds in Great Britain (2000 to 2013)

A key focus of the racing industry is to reduce the number of race-day events where horses die suddenly or are euthanased due to catastrophic injury. The objective of this study was therefore to determine risk factors for race-day fatalities in Thoroughbred racehorses, using a cohort of all horses participating in flat racing in Great Britain between 2000 and 2013. Horse-, race- and course-level data were collected and combined with all race-day fatalities, recorded by racecourse veterinarians in a central database. Associations between exposure variables and fatality were assessed using logistic regression analyses for (1) all starts in the dataset and (2) starts made on turf surfaces only. There were 806,764 starts in total, of which 548,571 were on turf surfaces. A total of 610 fatalities were recorded; 377 (61.8%) on turf. In both regression models, increased firmness of the going, increasing racing distance, increasing average horse performance, first year of racing and wearing eye cover for the first time all increased the odds of fatality. Generally, the odds of fatality also increased with increasing horse age whereas increasing number of previous starts reduced fatality odds. In the ‘all starts’ model, horses racing in an auction race were at 1.46 (95% confidence interval (CI) 1.06–2.01) times the odds of fatality compared with horses not racing in this race type. In the turf starts model, horses racing in Group 1 races were at 3.19 (95% CI 1.71–5.93) times the odds of fatality compared with horses not racing in this race type. Identification of novel risk factors including wearing eye cover and race type will help to inform strategies to further reduce the rate of fatality in flat racing horses, enhancing horse and jockey welfare and safety

Development of practice principles for the management of ongoing suicidal ideation in young people diagnosed with major depressive disorder

Objectives: There is a lack of clear guidance regarding the management of ongoing suicidality in young people experiencing major depressive disorder. This study utilised an expert consensus approach in identifying practice principles to complement relevant clinical guidelines for the treatment of major depressive disorder in young people. The study also sought to outline a broad treatment framework for clinical intervention with young people experiencing ongoing suicidal ideation. Methods: In-depth focus groups were undertaken with a specialist multidisciplinary clinical team (the Youth Mood Clinic at Orygen Youth Health Clinical Program, Melbourne) working with young people aged 15–25 years experiencing ongoing suicidal ideation. Each focus group was audio recorded and transcribed verbatim using orthographic conventions. Principles of grounded theory and thematic analysis were used to analyse and code the resultant data. Results: The identified codes were subsequently synthesised into eight practice principles reflecting engagement and consistency of care, ongoing risk assessment and documentation, individualised crisis planning, engaging systems of support, engendering hopefulness, development of adaptive coping, management of acute risk, and consultation and supervision. Conclusions: The identified practice principles provide a broad management framework, and may assist to improve treatment consistency and clinical management of young people experiencing ongoing suicidal ideation. The practice principles may be of use to health professionals working within a team-based setting involved in the provision of care, even if peripherally, to young people with ongoing suicidal ideation. Findings address the lack of treatment consistency and shared terminology and may provide containment and guidance to multidisciplinary clinicians working with this at-risk group

On the relative roles of dynamics and chemistry governing the abundance and diurnal variation of low latitude thermospheric nitric oxide

We use data from two NASA satellites, the Thermosphere Ionosphere Energetics and Dynamics (TIMED) and the Aeronomy of Ice in the Mesosphere (AIM) satellites in conjunction with model simulations from the Thermosphere-Ionosphere-Mesosphere-Electrodynamics General Circulation Model (TIME-GCM) to elucidate the key dynamical and chemical factors governing the abundance and diurnal variation of nitric oxide (NO) at near solar minimum conditions and low latitudes. This analysis was enabled by the recent orbital precession of the AIM satellite which caused the solar occultation pattern measured by the Solar Occultation for Ice Experiment (SOFIE) to migrate down to low and mid latitudes for specific periods of time. We use a month of NO data collected in January 2017 to compare with two versions of the TIME-GCM, one driven solely by climatological tides and analysis-derived planetary waves at the lower boundary and free running at all other altitudes, while the other is constrained by a high-altitude analysis from the Navy Global Environmental Model (NAVGEM)up to the mesopause. We also compare SOFIE data with a NO climatology from the Nitric Oxide Empirical Model (NOEM). Both SOFIE and NOEM yield peak NO abundances of around 4×107cm−3; however, the SOFIE profile peaks about 6-8 km lower than NOEM. We show that this difference is likely a local time effect; SOFIE being a dawn measurement and NOEM representing late morning/near noon. The constrained version of TIME-GCM exhibits a low altitude dawn peak while the model that is forced solely at the lower boundary and free running above does not. We attribute this difference due to a phase change in the semi-diurnal tide in the NAVGEM-constrained model causing descent of high NO mixing ratio air near dawn. This phase difference between the two models arises due to differences in the mesospheric zonal mean zonal winds. Regarding the absolute NO abundance, all versions of the TIME-GCM overestimate this. Tuning the model to yield calculated atomic oxygen in agreement with TIMED data helps, but is insufficient. Further, the TIME-GCM underestimates the electron density [e-] as compared with the International Reference Ionosphere empirical model. This suggests a potential conflict with the requirements of NO modeling and [e-] modeling since one solution typically used to increase model [e-] is to increase the solar soft X ray flux which would, in this case, worsen the NO model/data discrepancy

A genome-wide study of Hardy–Weinberg equilibrium with next generation sequence data

Statistical tests for Hardy–Weinberg equilibrium have been an important tool for detecting genotyping errors in the past, and remain important in the quality control of next generation sequence data. In this paper, we analyze complete chromosomes of the 1000 genomes project by using exact test procedures for autosomal and X-chromosomal variants. We find that the rate of disequilibrium largely exceeds what might be expected by chance alone for all chromosomes. Observed disequilibrium is, in about 60% of the cases, due to heterozygote excess. We suggest that most excess disequilibrium can be explained by sequencing problems, and hypothesize mechanisms that can explain exceptional heterozygosities. We report higher rates of disequilibrium for the MHC region on chromosome 6, regions flanking centromeres and p-arms of acrocentric chromosomes. We also detected long-range haplotypes and areas with incidental high disequilibrium. We report disequilibrium to be related to read depth, with variants having extreme read depths being more likely to be out of equilibrium. Disequilibrium rates were found to be 11 times higher in segmental duplications and simple tandem repeat regions. The variants with significant disequilibrium are seen to be concentrated in these areas. For next generation sequence data, Hardy–Weinberg disequilibrium seems to be a major indicator for copy number variation.Peer ReviewedPostprint (published version