Mutational analysis of the gene start sequences of pneumonia virus of mice

The transcriptional start sequence of pneumonia virus of mice is more variable than that of the other pneumoviruses, with five different nine-base gene start (GS) sequences found in the PVM genome. The sequence requirements of the PVM gene start signal, and the efficiency of transcriptional initiation of the different virus genes, was investigated using a reverse genetics approach with a minigenome construct containing two reporter genes. A series of GS mutants were created, where each of the nine bases of the gene start consensus sequence of a reporter gene was changed to every other possible base, and the resulting effect on initiation of transcription was assayed. Nucleotide positions 1, 2 and 7 were found to be most sensitive to mutation whilst positions 4, 5 and 9 were relatively insensitive. The L gene GS sequence was found to have only 20% of the activity of the consensus sequence whilst the published M2 gene start sequence was found to be non-functional. A minigenome construct in which the two reporter genes were separated by the F-M2 gene junction of PVM was used to confirm the presence of two alternative, functional, GS sequences that could both drive the transcription of the PVM M2 gene

?A confession of ignorance?: deaths from old age and deciphering cause-of-death statistics in Scotland, 1855?1949

A large amount of the research undertaken in an attempt to discover the reasons underlying the late nineteenth- and early twentieth-century mortality decline in Britain has relied on the statistics published by the Registrars General. The processes by which individual causes of death are recorded and then processed in order to create the statistics are not, however, well understood. In this article, the authors build on previous work to piece together a time series of causes of death for Scotland, which removes many of the discontinuities encountered in the published statistics that result from the Registrar General deciding to update the nosology, or classification system, which was being used to compile his figures. Having regrouped individual causes of death to ?smooth? the time series, the authors use the new groups to examine the changing causes of death in Scotland for selected age groups, before turning to undertake a detailed examination of mortality amongst those aged 55 or more. The authors find that when deaths from ?old age? in the latter age group are separated from other ?ill-defined? causes, it becomes obvious that there was a ?rebranding? of cause of death. The authors then use individual-level data from two Scottish communities to further dissect the roles played by ?informants? and ?doctors? in this rebranding, in order to see how these roles may have altered over time and what the consequences might be for one's view of how mortality changed in Scotland between 1855 and 1949. Finally, the authors argue that their findings have important implications for some of historical demography's most prominent theories: the McKeown thesis and the theory of epidemiological transition

Chapter 16 Volcanic hazard vulnerability on São Miguel Island, Azores

AbstractIn recent years much progress has been made in researching a wide variety of extreme events on São Miguel. In addition there are a number of volcano-related risks that impact upon the people of São Miguel. Some of these may occur both before and during volcanic emergencies (e.g. earthquakes), whilst others render São Miguel dangerous even when its volcanoes are not erupting (e.g. flooding, landslides, tsunamis and health impacts, especially the effects of CO2seepage into dwellings). In this chapter we first define what vulnerability means to the people of São Miguel, and relate this to the cultural and economic characteristics of the island. The following aspects of vulnerability are discussed: (a) physical (i.e. housing, settlement and the characteristics of evacuation routes and plans); (b) demographic and economic; and (c) social and cultural and perceptual (i.e. whether people have an accurate cognition of risk). Particular areas of concern relate to housing: the identification of isolated dwellings that would be difficult to evacuate; the vulnerability/resilience of evacuation routes following recent infrastructure improvements; characteristics of the island's transient population; management of livestock under emergency conditions; local leadership roles; and educational outreach.</jats:p

Estimating the incidence, prevalence and true cost of asthma in the UK: secondary analysis of national stand-alone and linked databases in England, Northern Ireland, Scotland and Wales-a study protocol.

INTRODUCTION: Asthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care. METHODS AND ANALYSIS: Secondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates. ETHICS AND DISSEMINATION: Approvals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map

Air Pollution, housing and respiratory tract Infections in Children: NatIonal birth Cohort study (PICNIC) - study protocol

INTRODUCTION: Respiratory tract infections (RTIs) are the most common reason for hospital admission among children <5 years in the UK. The relative contribution of ambient air pollution exposure and adverse housing conditions to RTI admissions in young children is unclear and has not been assessed in a UK context. METHODS AND ANALYSIS: The aim of the PICNIC study (Air Pollution, housing and respiratory tract Infections in Children: NatIonal birth Cohort Study) is to quantify the extent to which in-utero, infant and childhood exposures to ambient air pollution and adverse housing conditions are associated with risk of RTI admissions in children <5 years old. We will use national administrative data birth cohorts, including data from all children born in England in 2005-2014 and in Scotland in 1997-2020, created via linkage between civil registration, maternity and hospital admission data sets. We will further enhance these cohorts via linkage to census data on housing conditions and socioeconomic position and small area-level data on ambient air pollution and building characteristics. We will use time-to-event analyses to examine the association between air pollution, housing characteristics and the risk of RTI admissions in children, calculate population attributable fractions for ambient air pollution and housing characteristics, and use causal mediation analyses to explore the mechanisms through which housing and air pollution influence the risk of infant RTI admission. ETHICS, EXPECTED IMPACT AND DISSEMINATION: To date, we have obtained approval from six ethics and information governance committees in England and two in Scotland. Our results will inform parents, national and local governments, the National Health Service and voluntary sector organisations of the relative contribution of adverse housing conditions and air pollution to RTI admissions in young children. We will publish our results in open-access journals and present our results to the public via parent groups and social media and on the PICNIC website. Code and metadata will be published on GitHub

Rhythmic entrainment, syncopation and pleasantness

Although several authors have speculated that rhythmic entrainment induces positive affect (e.g. Juslin &amp; Vastfjäll, 2008; Clayton et al. 2004), so far there is no direct experimental evidence to support this claim. Therefore, the experiment hereby reported aimed to test the hypothesis that moving in time with music induces pleasantness and that this effect interacts with the level of syncopation of the music. Six short rhythmic musical stimuli with three levels of syncopation (low, medium, high), were presented to 77 participants, who were divided into two groups: one was asked to move along with the pulse of the music (by tapping with one foot), and the other was asked to listen without moving. The changes in the participants’ affective state were measured by using two techniques: self-report scales of pleasantness and arousal, and an indirect technique consisting of asking participants to evaluate the level of pleasantness expressed by emotionally ambiguous facial expressions –The perceived pleasantness works as an indicator of the observer’s own affective state (Niedenthal et al., 2000)-. It was predicted that: 1) intermediate levels of syncopation would be associated with the most pleasantness, and that 2) these effects would be larger in the ”˜tapping’ condition. The results revealed that even though the data from the indirect technique showed a trend in the predicted direction, there was a great amount of within-subjects variability which made these results unreliable. The data from self-reports supported the first prediction –participants experienced slightly higher levels of positive affect when tapping along to stimuli with a medium level of syncopation-; but not the second prediction –participants in the ”˜tapping’ condition did not experience more pleasantness nor unpleasantness than the participants in the ”˜stationary’ condition. No significant differences were found in any of the measures of arousal. These findings suggest that the effect of musical entrainment on the induction of pleasantness is primarily the result of the expectations aroused by syncopated rhythms, not by the movements made by the listener.References Clayton, M., Sager, R., &amp; Will, U. (2004). In time with the music: The concept of entrainment and its significance for ethnomusicology. ESEM CounterPoint, 1, 1–45.Juslin, P. N., &amp; Västfjäll, D. (2008). Emotional responses to music: the need to consider underlying mechanisms. The Behavioral and Brain Sciences, 31(5), 559–75; discussion 575–621. doi:10.1017/S0140525X08005293Niedenthal, P. M., Halberstadt, J. B., &amp; Margolin, J. (2000). Emotional state and the detection of change in facial expression of emotion. European Journal of Social Psychology, 30(May 1999), 211–223

Age, sex, and socioeconomic differences in multimorbidity measured in four ways:UK primary care cross-sectional analysis

Background: Multimorbidity poses major challenges to healthcare systems worldwide. Definitions with cut-offs in excess of ≥2 long-term conditions (LTCs) might better capture populations with complexity but are not standardised. Aim: To examine variation in prevalence using different definitions of multimorbidity. Design and setting: Cross-sectional study of 1 168 620 people in England. Method: Comparison of multimorbidity (MM) prevalence using four definitions: MM2+ (≥2 LTCs), MM3+ (≥3 LTCs), MM3+ from 3+ (≥3 LTCs from ≥3 International Classification of Diseases, 10th revision chapters), and mental–physical MM (≥2 LTCs where ≥1 mental health LTC and ≥1 physical health LTC are recorded). Logistic regression was used to examine patient characteristics associated with multimorbidity under all four definitions. Results: MM2+ was most common (40.4%) followed by MM3+ (27.5%), MM3+ from 3+ (22.6%), and mental–physical MM (18.9%). MM2+, MM3+, and MM3+ from 3+ were strongly associated with oldest age (adjusted odds ratio [aOR] 58.09, 95% confidence interval [CI] = 56.13 to 60.14; aOR 77.69, 95% CI = 75.33 to 80.12; and aOR 102.06, 95% CI = 98.61 to 105.65; respectively), but mental–physical MM was much less strongly associated (aOR 4.32, 95% CI = 4.21 to 4.43). People in the most deprived decile had equivalent rates of multimorbidity at a younger age than those in the least deprived decile. This was most marked in mental–physical MM at 40–45 years younger, followed by MM2+ at 15–20 years younger, and MM3+ and MM3+ from 3+ at 10–15 years younger. Females had higher prevalence of multimorbidity under all definitions, which was most marked for mental–physical MM. Conclusion: Estimated prevalence of multimorbidity depends on the definition used, and associations with age, sex, and socioeconomic position vary between definitions. Applicable multimorbidity research requires consistency of definitions across studies

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis : a record linkage analysis of Scottish healthcare databases

This study was commissioned by GSK through the Farr Institute/SHIP/eDRIS single portal. DJM is a Clinician Scientist Fellow funded by the Health Foundation/Academy of Medical Sciences.Objectives: Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. Setting: Health boards in Scotland (n=4). Participants: We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. Methods: Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. Results: 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30-39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. Conclusions: National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high.Publisher PDFPeer reviewe