Anaesthesia with dexmedetomidine and remifentanil in a child with mitochondrial myopathy

Patients with mitochondrial disorders have complex physiological issues which create a challenging scenario with regard to the safe provision of anaesthetic care. Within the spectrum of mitochondrial disorders, patients can be susceptible to multiple adverse effects and drug reactions from medications used during general anaesthesia. Although recent evidence suggests that inhalational anaesthetic agents may be used in patients with mitochondrial disorders, there is still a preference among some anaesthesia providers to use total intravenous anaesthesia (TIVA). In most scenarios, when TIVA is chosen, propofol is a major component. However, as a result of using propofol, patients with mitochondrial disorders may be susceptible to an acute metabolic crisis. It has been postulated that propofol, especially when given in large dosages, or when infused for prolonged periods of time, can adversely affect the function of the abnormal mitochondria that are present in patients with mitochondrial disorders. We present our experience with the use of dexmedetomidine as the primary component of a general anaesthetic regimen in a 10-year-old girl with a mitochondrial disorder and dystonia, who required anaesthetic care during a urological procedure. Previous reports on the use of dexmedetomidine as part of TIVA in patients susceptible to malignant hyperthermia are reviewed, and its benefits in patients with mitochondrial disorders, discussed. Additional concerns regarding the perioperative care of patients with mitochondrial disorders are deliberated.Keywords: dexmedetomidine, malignant hyperthermia, mitochondrial myopath

Do children's expectations about future physical activity predict their physical activity in adulthood?

BACKGROUND: Much of the population fails to meet recommended physical activity (PA) levels, but there remains considerable individual variation. By understanding drivers of different trajectories, interventions can be better targeted and more effective. One such driver may be a person's physical activity identity (PAI)-the extent to which a person perceives PA as central to who they are. METHODS: Using survey information and a unique body of essays written at age 11 from the National Child Development Study (N = 10 500), essays mentioning PA were automatically identified using the machine learning technique support vector classification and PA trajectories were estimated using latent class analysis. Analyses tested the extent to which childhood PAI correlated with activity levels from age 23 through 55 and with trajectories across adulthood. RESULTS: 42.2% of males and 33.5% of females mentioned PA in their essays, describing active and/or passive engagement. Active PAI in childhood was correlated with higher levels of activity for men but not women, and was correlated with consistently active PA trajectories for both genders. Passive PAI was not related to PA for either gender. CONCLUSIONS: This study offers a novel approach for analysing large qualitative datasets to assess identity and behaviours. Findings suggest that at as young as 11 years old, the way a young person conceptualizes activity as part of their identity has a lasting association with behaviour. Still, an active identity may require a supportive sociocultural context to manifest in subsequent behaviour

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Leukocyte adhesion deficiency-I: A comprehensive review of all published cases

Leukocyte adhesion deficiency-I (LAD-I) is a rare, serious disorder with severity determined by defective CD18 expression. LAD-I is characterized by umbilical complications, granulocytosis, and diverse infections. Severe LAD-I is frequently fatal before the age of 2 years without allogeneic transplant. We identified 323 cases published between 1975 and 2017

β-Arrestin-2 regulates the development of allergic asthma

Asthma is a chronic inflammatory disorder of the airways that is coordinated by Th2 cells in both human asthmatics and animal models of allergic asthma. Migration of Th2 cells to the lung is key to their inflammatory function and is regulated in large part by chemokine receptors, members of the seven-membrane-spanning receptor family. It has been reported recently that T cells lacking β-arrestin-2, a G protein-coupled receptor regulatory protein, demonstrate impaired migration in vitro. Here we show that allergen-sensitized mice having a targeted deletion of the β-arrestin-2 gene do not accumulate T lymphocytes in their airways, nor do they demonstrate other physiological and inflammatory features characteristic of asthma. In contrast, the airway inflammatory response to LPS, an event not coordinated by Th2 cells, is fully functional in mice lacking β-arrestin-2. β-arrestin-2-deficient mice demonstrate OVA-specific IgE responses, but have defective macrophage-derived chemokine-mediated CD4+ T cell migration to the lung. This report provides the first evidence that β-arrestin-2 is required for the manifestation of allergic asthma. Because β-arrestin-2 regulates the development of allergic inflammation at a proximal step in the inflammatory cascade, novel therapies focused on this protein may prove useful in the treatment of asthma

‘Like the stranger at a funeral who cries more than the bereaved’: ethical dilemmas in ethnographic research with children

This article contributes to debates on the practicality and utility of prior ethical review in ethnography and qualitative research using an ethnography of children’s involvement in artisanal gold mining work in Ghana as a case study. Reflecting on dilemmas and obstacles encountered in attempts to employ prescribed institutional ethical guidance modelled for childhood research in the UK during the fieldwork, the discussion brings to attention some of the problems that can arise when ethical guidance is not anchored in the lived realities or value systems of the setting in which fieldwork is conducted. The article seeks to rejuvenate calls for more flexible and socio-culturally responsive ethical review and practice as an alternative to the prescriptive ethical regimes

Multivariate discrimination and the Higgs + W/Z search

A systematic method for optimizing multivariate discriminants is developed and applied to the important example of a light Higgs boson search at the Tevatron and the LHC. The Significance Improvement Characteristic (SIC), defined as the signal efficiency of a cut or multivariate discriminant divided by the square root of the background efficiency, is shown to be an extremely powerful visualization tool. SIC curves demonstrate numerical instabilities in the multivariate discriminants, show convergence as the number of variables is increased, and display the sensitivity to the optimal cut values. For our application, we concentrate on Higgs boson production in association with a W or Z boson with H -> bb and compare to the irreducible standard model background, Z/W + bb. We explore thousands of experimentally motivated, physically motivated, and unmotivated single variable discriminants. Along with the standard kinematic variables, a number of new ones, such as twist, are described which should have applicability to many processes. We find that some single variables, such as the pull angle, are weak discriminants, but when combined with others they provide important marginal improvement. We also find that multiple Higgs boson-candidate mass measures, such as from mild and aggressively trimmed jets, when combined may provide additional discriminating power. Comparing the significance improvement from our variables to those used in recent CDF and DZero searches, we find that a 10-20% improvement in significance against Z/W + bb is possible. Our analysis also suggests that the H + W/Z channel with H -> bb is also viable at the LHC, without requiring a hard cut on the W/Z transverse momentum.Comment: 41 pages, 5 tables, 29 figure

The impact of measurement error in modelled ambient particles exposures on health effect estimates in multi-level analysis: a simulation study.

Background: Various spatiotemporal models have been proposed for predicting ambient particulate exposure for inclusion in epidemiological analyses. We investigated the effect of measurement error in the prediction of particulate matter with diameter <10 µm (PM10) and <2.5 µm (PM2.5) concentrations on the estimation of health effects. Methods: We sampled 1,000 small administrative areas in London, United Kingdom, and simulated the “true” underlying daily exposure surfaces for PM10 and PM2.5 for 2009–2013 incorporating temporal variation and spatial covariance informed by the extensive London monitoring network. We added measurement error assessed by comparing measurements at fixed sites and predictions from spatiotemporal land-use regression (LUR) models; dispersion models; models using satellite data and applying machine learning algorithms; and combinations of these methods through generalized additive models. Two health outcomes were simulated to assess whether the bias varies with the effect size. We applied multilevel Poisson regression to simultaneously model the effect of long- and short-term pollutant exposure. For each scenario, we ran 1,000 simulations to assess measurement error impact on health effect estimation. Results: For long-term exposure to particles, we observed bias toward the null, except for traffic PM2.5 for which only LUR underestimated the effect. For short-term exposure, results were variable between exposure models and bias ranged from −11% (underestimate) to 20% (overestimate) for PM10 and of −20% to 17% for PM2.5. Integration of models performed best in almost all cases. Conclusions: No single exposure model performed optimally across scenarios. In most cases, measurement error resulted in attenuation of the effect estimate

A survey of statistics in three UK general practice journal

Background Many medical specialities have reviewed the statistical content of their journals. To our knowledge this has not been done in general practice. Given the main role of a general practitioner as a diagnostician we thought it would be of interest to see whether the statistical methods reported reflect the diagnostic process. Methods Hand search of three UK journals of general practice namely the British Medical Journal (general practice section), British Journal of General Practice and Family Practice over a one-year period (1 January to 31 December 2000). Results A wide variety of statistical techniques were used. The most common methods included t-tests and Chi-squared tests. There were few articles reporting likelihood ratios and other useful diagnostic methods. There was evidence that the journals with the more thorough statistical review process reported a more complex and wider variety of statistical techniques. Conclusions The BMJ had a wider range and greater diversity of statistical methods than the other two journals. However, in all three journals there was a dearth of papers reflecting the diagnostic process. Across all three journals there were relatively few papers describing randomised controlled trials thus recognising the difficulty of implementing this design in general practice