Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation

Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called “ClimGen”. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods

Establishing comprehensive oral assessments for children with safeguarding concerns.

The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule.

Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. IMPORTANCE: The capsule determines >90 different pneumococcal serotypes, which vary in capsule size, virulence, duration, and prevalence of carriage. Current serotype-specific vaccines elicit anticapsule antibodies. Pneumococcus can take up exogenous DNA by transformation and insert it into its chromosome by homologous recombination. This mechanism has disseminated drug resistance and generated vaccine escape variants. It is hence crucial to pneumococcal evolutionary response to interventions, but there has been no systematic study quantifying whether serotypes vary in recombination and whether this is associated with serotype-specific properties such as capsule size or carriage duration. Larger capsules could physically inhibit DNA uptake, or given the longer carriage duration for larger capsules, this may promote recombination. We find that recombination varies among capsules and is associated with capsule size, carriage duration, and carriage prevalence and negatively associated with invasiveness. The consequence of this work is that serotypes with different capsules may respond differently to selective pressures like vaccines

Childbearing intentions in a low fertility context: the case of Romania

This paper applies the Theory of Planned Behaviour (TPB) to find out the predictors of fertility intentions in Romania, a low-fertility country. We analyse how attitudes, subjective norms and perceived behavioural control relate to the intention to have a child among childless individuals and one-child parents. Principal axis factor analysis confirms which items proposed by the Generation and Gender Survey (GGS 2005) act as valid and reliable measures of the suggested theoretical socio-psychological factors. Four parity-specific logistic regression models are applied to evaluate the relationship between the socio-psychological factors and childbearing intentions. Social pressure emerges as the most important aspect in fertility decision-making among childless individuals and one-child parents, and positive attitudes towards childbearing are a strong component in planning for a child. This paper also underlines the importance of the region-specific factors when studying childbearing intentions: planning for the second child significantly differs among the development regions, representing the cultural and socio-economic divisions of the Romanian territory

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Intrinsic activity in the fly brain gates visual information during behavioral choices

The small insect brain is often described as an input/output system that executes reflex-like behaviors. It can also initiate neural activity and behaviors intrinsically, seen as spontaneous behaviors, different arousal states and sleep. However, less is known about how intrinsic activity in neural circuits affects sensory information processing in the insect brain and variability in behavior. Here, by simultaneously monitoring Drosophila's behavioral choices and brain activity in a flight simulator system, we identify intrinsic activity that is associated with the act of selecting between visual stimuli. We recorded neural output (multiunit action potentials and local field potentials) in the left and right optic lobes of a tethered flying Drosophila, while its attempts to follow visual motion (yaw torque) were measured by a torque meter. We show that when facing competing motion stimuli on its left and right, Drosophila typically generate large torque responses that flip from side to side. The delayed onset (0.1-1 s) and spontaneous switch-like dynamics of these responses, and the fact that the flies sometimes oppose the stimuli by flying straight, make this behavior different from the classic steering reflexes. Drosophila, thus, seem to choose one stimulus at a time and attempt to rotate toward its direction. With this behavior, the neural output of the optic lobes alternates; being augmented on the side chosen for body rotation and suppressed on the opposite side, even though the visual input to the fly eyes stays the same. Thus, the flow of information from the fly eyes is gated intrinsically. Such modulation can be noise-induced or intentional; with one possibility being that the fly brain highlights chosen information while ignoring the irrelevant, similar to what we know to occur in higher animals

Foot pain and foot health in an educated population of adults: results from the Glasgow Caledonian University Alumni Foot Health Survey

Abstract Background Foot pain is common amongst the general population and impacts negatively on physical function and quality of life. Associations between personal health characteristics, lifestyle/behaviour factors and foot pain have been studied; however, the role of wider determinants of health on foot pain have received relatively little attention. Objectives of this study are i) to describe foot pain and foot health characteristics in an educated population of adults; ii) to explore associations between moderate-to-severe foot pain and a variety of factors including gender, age, medical conditions/co-morbidity/multi-morbidity, key indicators of general health, foot pathologies, and social determinants of health; and iii) to evaluate associations between moderate-to-severe foot pain and foot function, foot health and health-related quality-of-life. Methods Between February and March 2018, Glasgow Caledonian University Alumni with a working email address were invited to participate in the cross-sectional electronic survey (anonymously) by email via the Glasgow Caledonian University Alumni Office. The survey was constructed using the REDCap secure web online survey application and sought information on presence/absence of moderate-to-severe foot pain, patient characteristics (age, body mass index, socioeconomic status, occupation class, comorbidities, and foot pathologies). Prevalence data were expressed as absolute frequencies and percentages. Multivariate logistic and linear regressions were undertaken to identify associations 1) between independent variables and moderate-to-severe foot pain, and 2) between moderate-to-severe foot pain and foot function, foot health and health-related quality of life. Results Of 50,228 invitations distributed, there were 7707 unique views and 593 valid completions (median age [inter-quartile range] 42 [31–52], 67.3% female) of the survey (7.7% response rate). The sample was comprised predominantly of white Scottish/British (89.4%) working age adults (95%), the majority of whom were overweight or obese (57.9%), and in either full-time or part-time employment (82.5%) as professionals (72.5%). Over two-thirds (68.5%) of the sample were classified in the highest 6 deciles (most affluent) of social deprivation. Moderate-to-severe foot pain affected 236/593 respondents (39.8%). High body mass index, presence of bunions, back pain, rheumatoid arthritis, hip pain and lower occupation class were included in the final multivariate model and all were significantly and independently associated with moderate-to-severe foot pain (p < 0.05), except for rheumatoid arthritis (p = 0.057). Moderate-to-severe foot pain was significantly and independently associated lower foot function, foot health and health-related quality of life scores following adjustment for age, gender and body mass index (p < 0.05). Conclusions Moderate-to-severe foot pain was highly prevalent in a university-educated population and was independently associated with female gender, high body mass index, bunions, back pain, hip pain and lower occupational class. Presence of moderate-to-severe foot pain was associated with worse scores for foot function, foot health and health-related quality-of-life. Education attainment does not appear to be protective against moderate-to-severe foot pain

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802