Separating the role of direct radiative heating and photolysis in modulating the atmospheric response to the amplitude of the 11-year solar cycle forcing

The atmospheric response to the 11-year solar cycle is separated into the contributions from changes in direct radiative heating and photolysis rates using specially designed sensitivity simulations with the UM-UKCA (Unified Model coupled to the United Kingdom Chemistry and Aerosol model) chemistry–climate model. We perform a number of idealised time-slice experiments under perpetual solar maximum (SMAX) and minimum conditions (SMIN), and we find that contributions from changes in direct heating and photolysis rates are both important for determining the stratospheric shortwave heating, temperature and ozone responses to the amplitude of the 11-year solar cycle. The combined effects of the processes are found to be largely additive in the tropics but nonadditive in the Southern Hemisphere (SH) high latitudes during the dynamically active season. Our results indicate that, in contrast to the original mechanism proposed in the literature, the solar-induced changes in the horizontal shortwave heating rate gradients not only in autumn/early winter but throughout the dynamically active season are important for modulating the dynamical response to changes in solar forcing. In spring, these gradients are strongly influenced by the shortwave heating anomalies at higher southern latitudes, which are closely linked to the concurrent changes in ozone. In addition, our simulations indicate differences in the winter SH dynamical responses between the experiments. We suggest a couple of potential drivers of the simulated differences, i.e. the role of enhanced zonally asymmetric ozone heating brought about by the increased solar-induced ozone levels under SMAX and/or sensitivity of the polar dynamical response to the altitude of the anomalous radiative tendencies. All in all, our results suggest that solar-induced changes in ozone, both in the tropics/mid-latitudes and the polar regions, are important for modulating the SH dynamical response to the 11-year solar cycle. In addition, the markedly nonadditive character of the SH polar vortex response simulated in austral spring highlights the need for consistent model implementation of the solar cycle forcing in both the radiative heating and photolysis schemes

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Combining PPI with qualitative research to engage ‘harder-to-reach’ populations: service user groups as co-applicants on a platform study for a trial

Abstract Background: Patient and public involvement (PPI) in all research studies is recommended from the earliest point and in as many stages as possible. Qualitative research is also recommended in the early stages of designing. complex intervention trials. Combining both together might enable inclusion of ‘harder-to-reach’ perspectives from the target population(s), particularly when the research is intended for their benefit. However, the interface between PPI and qualitative research has received little attention. Methods: In a multi-disciplinary, mixed methods study to inform the design of incentive trials for smoking cessation in pregnancy and breastfeeding, we combined PPI and qualitative research, with some overlap. Mother and baby groups from two geographically separate disadvantaged areas, with diverse experiences of the smoking and breastfeeding, but no training or previous involvement in research, were recruited as PPI research grant co-applicants. An iterative partnership approach facilitated involvement in research conduct and design across all project phases. Group PPI members were also invited to contribute to more formal qualitative data collection, as and when indicated by the research questions, and emerging analysis. Results: We engaged with ‘harder-to-reach’ women in mother and baby group settings, rather than in academic or home environments. These settings were relaxed and informal, which facilitated rapport-building, disclosures of unexpected information and maintained trust. 21 women participated in standard PPI activities: feedback on study protocols and documents; piloting questionnaires and interview schedules. PPI members voiced some different perspectives from those captured within the qualitative dataset. 19 participated in focused qualitative research. Novel aspects were audio recorded PPI discussions, which contributed qualitative data; first, to interpret systematic review findings and construct intervention vignettes for use in the qualitative research; second, to assist with recruitment to improve sample diversity in the formal qualitative dataset; and third, to translate theory and findings presented in a researcher generated logic model into a lay tool. This had face validity for potential trial participants and used the metaphor of a ladder. Conclusions: Combining and overlapping PPI and qualitative research added ‘harder-to-reach’ contributions, sample diversity, trust and engagement in creative approaches beyond what could be achieved through PPI or qualitative research alone. (350/350

Persistence of Pathogens with Short Infectious Periods in Seasonal Tick Populations: The Relative Importance of Three Transmission Routes

BACKGROUND: The flaviviruses causing tick-borne encephalitis (TBE) persist at low but consistent levels in tick populations, despite short infectious periods in their mammalian hosts and transmission periods constrained by distinctly seasonal tick life cycles. In addition to systemic and vertical transmission, cofeeding transmission has been proposed as an important route for the persistence of TBE-causing viruses. Because cofeeding transmission requires ticks to feed simultaneously, the timing of tick activity may be critical to pathogen persistence. Existing models of tick-borne diseases do not incorporate all transmission routes and tick seasonality. Our aim is to evaluate the influence of seasonality on the relative importance of different transmission routes by using a comprehensive mathematical model. METHODOLOGY/PRINCIPAL FINDINGS: We developed a stage-structured population model that includes tick seasonality and evaluated the relative importance of the transmission routes for pathogens with short infectious periods, in particular Powassan virus (POWV) and the related "deer tick virus," emergent encephalitis-causing flaviviruses in North America. We used the next generation matrix method to calculate the basic reproductive ratio and performed elasticity analyses. We confirmed that cofeeding transmission is critically important for such pathogens to persist in seasonal tick populations over the reasonable range of parameter values. At higher but still plausible rates of vertical transmission, our model suggests that vertical transmission can strongly enhance pathogen prevalence when it operates in combination with cofeeding transmission. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the consistent prevalence of POWV observed in tick populations could be maintained by a combination of low vertical, intermediate cofeeding and high systemic transmission rates. When vertical transmission is weak, nymphal ticks support integral parts of the transmission cycle that are critical for maintaining the pathogen. We also extended the model to pathogens that cause chronic infections in hosts and found that cofeeding transmission could contribute to elevating prevalence even in these systems. Therefore, the common assumption that cofeeding transmission is not relevant in models of chronic host infection, such as Lyme disease, could lead to underestimating pathogen prevalence

Children’s sedentary behaviour: descriptive epidemiology and associations with objectively-measured sedentary time

Background: Little is known regarding the patterning and socio-demographic distribution of multiple sedentary behaviours in children. The aims of this study were to: 1) describe the leisure-time sedentary behaviour of 9-10 year old British children, and 2) establish associations with objectively-measured sedentary time. Methods: Cross-sectional analysis in the SPEEDY study (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people) (N=1513, 44.3% boys). Twelve leisure-time sedentary behaviours were assessed by questionnaire. Objectively-measured leisure-time sedentary time (Actigraph GT1M, <100 counts/minute) was assessed over 7 days. Differences by sex and socioeconomic status (SES) in self-reported sedentary behaviours were tested using Kruskal-Wallis tests. The association between objectively-measured sedentary time and the separate sedentary behaviours (continuous (minutes) and categorised into 'none' 'low' or 'high' participation) was assessed using multi-level linear regression. Results: Sex differences were observed for time spent in most sedentary behaviours (all p ≤ 0.02), except computer use. Girls spent more time in combined non-screen sedentary behaviour (median, interquartile range: girls: 770.0 minutes, 390.0-1230.0; boys: 725.0, 365.0 - 1182.5; p = 0.003), whereas boys spent more time in screen-based behaviours (girls: 540.0, 273.0 - 1050.0; boys: 885.0, 502.5 - 1665.0; p < 0.001). Time spent in five non-screen behaviours differed by SES, with higher values in those of higher SES (all p ≤ 0.001). Regression analyses with continuous exposures indicated that reading (β = 0.1, p < 0.001) and watching television (β = 0.04, p < 0.01) were positively associated with objectively-measured sedentary time, whilst playing board games (β = -0.12, p < 0.05) was negatively associated. Analysed in categorical form, sitting and talking (vs. none: 'low' β = 26.1,ns; 'high' 30.9, p < 0.05), playing video games (vs. none: 'low' β = 49.1, p < 0.01; 'high' 60.2, p < 0.01) and watching television (vs. lowest tertile: middle β = 22.2,ns; highest β = 31.9, p < 0.05) were positively associated with objectively-measured sedentary time whereas talking on the phone (vs. none: 'low' β = -38.5, p < 0.01; 'high' -60.2, p < 0.01) and using a computer/internet (vs. none: 'low' β = -30.7, p < 0.05; 'high' -4.2,ns) were negatively associated. Conclusions: Boys and girls and children of different socioeconomic backgrounds engage in different leisure-time sedentary behaviours. Whilst a number of behaviours may be predictive of total sedentary time, collectively they explain little overall variance. Future studies should consider a wide range of sedentary behaviours and incorporate objective measures to quantify sedentary time where possible

Firm insoles effectively reduce hemolysis in runners during long distance running - a comparative study

<p>Abstract</p> <p>Background</p> <p>Shock absorbing insoles are effective in reducing the magnitude and rate of loading of peak impact forces generated at foot strike during running, whereas the foot impact force during running has been considered to be an important cause of intravascular hemolysis in long distance runners. Objective of this study was to evaluate the intravascular hemolysis during running and compare the effect of two different types of insoles (Soft and Firm) on hemolysis.</p> <p>Methods</p> <p>Twenty male long and middle distance runners volunteered to participate in this study. We selected two insoles (Soft and Firm) according to their hardness level (SHORE 'A' scale). Participants were randomly assigned to the soft insole (group 1) and firm insole (group 2) group with ten athletes in each group. Each athlete completed one hour of running at the calculated target heart rate (60-70%). Venous blood samples were collected before and immediately after running. We measured unconjucated bilirubin (mg/dl), lactate dehydrogenase (μ/ml), hemoglobin (g/l) and serum ferritin (ng/ml) as indicators of hemolysis.</p> <p>Results</p> <p>Our study revealed a significant increase in the mean values of unconjucated bilirubin (P < 0.05) while running with soft insoles indicating the occurrence of hemolysis in this group of athletes. Graphical analysis revealed an inverse relationship between hardness of insoles and hemolysis for the observed values.</p> <p>Conclusion</p> <p>Our results indicate that intravascular hemolysis occurs in athletes during long distance running and we conclude that addition of firm insoles effectively reduces the amount of hemolysis in runners compared to soft insoles.</p

Human Mesenchymal Stem Cells Protect Human Islets from Pro-Inflammatory Cytokines

Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0×106 human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0×106 bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation