The contribution of multiple long-term conditions to widening inequalities in disability-free life expectancy over two decades: Longitudinal analysis of two cohorts using the Cognitive Function and Ageing Studies.

BACKGROUND: : Disability-free life expectancy (DFLE) inequalities by socioeconomic deprivation are widening, alongside rising prevalence of multiple long-term conditions (MLTCs). We use longitudinal data to assess whether MLTCs contribute to the widening DFLE inequalities by socioeconomic deprivation. METHODS: : The Cognitive Function and Ageing Studies (CFAS I and II) are large population-based studies of those ≥65 years, conducted in three areas in England. Baseline occurred in 1991 (CFAS I, n=7635) and 2011 (CFAS II, n=7762) with two-year follow-up. We defined disability as difficulty in activities of daily living, MLTCs as the presence of at least two of nine health conditions, and socioeconomic deprivation by area-level deprivation tertiles. DFLE and transitions between disability states and death were estimated from multistate models. FINDINGS: : For people with MLTCs, inequalities in DFLE at age 65 between the most and least affluent widened to around 2.5 years (men:2.4 years, 95% confidence interval (95%CI) 0.4-4.4; women:2.6 years, 95%CI 0.7-4.5) by 2011. Incident disability reduced for the most affluent women (Relative Risk Ratio (RRR):0.6, 95%CI 0.4-0.9), and mortality with disability reduced for least affluent men (RRR:0.6, 95%CI 0.5-0.8). MLTCs prevalence increased only for least affluent men (1991: 58.8%, 2011: 66.9%) and women (1991: 60.9%, 2011: 69.1%). However, DFLE inequalities were as large in people without MLTCs (men:2.4 years, 95%CI 0.3-4.5; women:3.1 years, 95% CI 0.8-5.4). INTERPRETATION: : Widening DFLE inequalities were not solely due to MLTCs. Reduced disability incidence with MLTCs is possible but was only achieved in the most affluent

Bait preferences of Australian dung beetles (Coleoptera: Scarabaeidae) in tropical and subtropical Queensland forests

Dung beetles (Scarabaeinae) are mainly coprophagous. Globally, many species co-exist with large mammalian fauna in grasslands and savannahs. However, tropical and subtropical rainforests, where large herbivorous mammals are scarce, support numerous dung beetle species. Many rainforest dung beetles have been shown to be generalist saprophages or specialists on non-dung food resources. In Australian rainforests, observations of native dung beetles have indicated that some species are attracted to other resources such as fruit or fungi, although the extent to which this occurs is not known. To learn more about the diet breadth of Australian native rainforest dung beetles, we assessed their attraction to a range of baits, including two types of dung, four types of carrion from both vertebrates and invertebrates, three types of rotting fruit and rotting mushrooms. We primarily surveyed rainforest sites but included two dry open-forest sites for comparisons. Of the two groups of Australian native dung beetles (Onthophagini and Australian endemic genera), the latter dominated the rainforest dung beetle fauna and were attracted to a greater variety of baits compared with Onthophagini. The Onthophagini were dominant in open forest and were more likely to be attracted to a particular bait type, primarily dung. Our findings suggest that many of the species belonging to the ‘Australian endemic genera’ are generalist feeders and their ability to utilise a range of food resources contributes to their abundance and diversity in Australian rainforests

Combined effects of time spent in physical activity, sedentary behaviors and sleep on obesity and cardio-metabolic health markers: a novel compositional data analysis approach

<div><p>The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity.</p></div

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Citizenship:Contrasting Dynamics at the Interface of Integration and Constitutionalism

EUDO Citizenship ObservatoryThis paper explores the different ways in which citizenship has played a role in polity formation in the context of the European Union. It focuses on both the ‘integration’ and the ‘constitution’ dimensions. The paper thus has two substantive sections. The first addresses the role of citizenship of the Union, examining the dynamic relationship between this concept, the role of the Court of Justice, and the free movement dynamic of EU law. The second turns to citizenship in the Union, looking at some recent political developments under which concepts of citizenship, and democratic membership as a key dimension of citizenship, have been given greater prominence. One key finding of the paper is that there is a tension between citizenship of the Union, as part of the EU's ‘old’ incremental constitutionalism based on the constitutionalisation of the existing Treaties, and citizenship in the Union, where the possibilities of a ‘new’ constitutionalism based on renewed constitutional documents have yet to be fully realise

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Development of a questionnaire to assess sedentary time in older persons -- a comparative study using accelerometry

Background: There is currently no validated questionnaire available to assess total sedentary time in older adults. Most studies only used TV viewing time as an indicator of sedentary time. The first aim of our study was to investigate the self-reported time spent by older persons on a set of sedentary activities, and to compare this with objective sedentary time measured by accelerometry. The second aim was to determine what set of self-reported sedentary activities should be used to validly rank people's total sedentary time. Finally we tested the reliability of our newly developed questionnaire using the best performing set of sedentary activities. Methods. The study sample included 83 men and women aged 65-92 y, a random sample of Longitudinal Aging Study Amsterdam participants, who completed a questionnaire including ten sedentary activities and wore an Actigraph GT3X accelerometer for 8 days. Spearman correlation coefficients were calculated to examine the association between self-reported time and objective sedentary time. The test-retest reliability was calculated using the intraclass correlation coefficient (ICC). Results: Mean total self-reported sedentary time was 10.4 (SD 3.5) h/d and was not significantly different from mean total objective sedentary time (10.2 (1.2) h/d, p = 0.63). Total self-reported sedentary time on an average day (sum of ten activities) correlated moderately (Spearman's r = 0.35, p < 0.01) with total objective sedentary time. The correlation improved when using the sum of six activities (r = 0.46, p < 0.01), and was much higher than when using TV watching only (r = 0.22, p = 0.05). The test-retest reliability of the sum of six sedentary activities was 0.71 (95% CI 0.57-0.81). Conclusions: A questionnaire including six sedentary activities was moderately associated with accelerometry-derived sedentary time and can be used to reliably rank sedentary time in older persons. © 2013 Visser and Koster; licensee BioMed Central Ltd

NetTurnP – Neural Network Prediction of Beta-turns by Use of Evolutionary Information and Predicted Protein Sequence Features

UNLABELLED: β-turns are the most common type of non-repetitive structures, and constitute on average 25% of the amino acids in proteins. The formation of β-turns plays an important role in protein folding, protein stability and molecular recognition processes. In this work we present the neural network method NetTurnP, for prediction of two-class β-turns and prediction of the individual β-turn types, by use of evolutionary information and predicted protein sequence features. It has been evaluated against a commonly used dataset BT426, and achieves a Matthews correlation coefficient of 0.50, which is the highest reported performance on a two-class prediction of β-turn and not-β-turn. Furthermore NetTurnP shows improved performance on some of the specific β-turn types. In the present work, neural network methods have been trained to predict β-turn or not and individual β-turn types from the primary amino acid sequence. The individual β-turn types I, I', II, II', VIII, VIa1, VIa2, VIba and IV have been predicted based on classifications by PROMOTIF, and the two-class prediction of β-turn or not is a superset comprised of all β-turn types. The performance is evaluated using a golden set of non-homologous sequences known as BT426. Our two-class prediction method achieves a performance of: MCC=0.50, Qtotal=82.1%, sensitivity=75.6%, PPV=68.8% and AUC=0.864. We have compared our performance to eleven other prediction methods that obtain Matthews correlation coefficients in the range of 0.17-0.47. For the type specific β-turn predictions, only type I and II can be predicted with reasonable Matthews correlation coefficients, where we obtain performance values of 0.36 and 0.31, respectively. CONCLUSION: The NetTurnP method has been implemented as a webserver, which is freely available at http://www.cbs.dtu.dk/services/NetTurnP/. NetTurnP is the only available webserver that allows submission of multiple sequences

Genetic and Chemical Evaluation of Trypanosoma brucei Oleate Desaturase as a Candidate Drug Target

Background: Trypanosomes can synthesize polyunsaturated fatty acids. Previously, we have shown that they possess stearoyl-CoA desaturase (SCD) and oleate desaturase (OD) to convert stearate (C18) into oleate (C18:1) and linoleate (C18:2), respectively. Here we examine if OD is essential to these parasites. Methodology: Cultured procyclic (insect-stage) form (PCF) and bloodstream-form (BSF) Trypanosoma brucei cells were treated with 12- and 13-thiastearic acid (12-TS and 13-TS), inhibitors of OD, and the expression of the enzyme was knocked down by RNA interference. The phenotype of these cells was studied. Principal Findings: Growth of PCF T. brucei was totally inhibited by 100 mM of 12-TS and 13-TS, with EC50 values of 4062 and 3062 mM, respectively. The BSF was more sensitive, with EC50 values of 763 and 261 mM, respectively. This growth phenotype was due to the inhibitory effect of thiastearates on OD and, to a lesser extent, on SCD. The enzyme inhibition caused a drop in total unsaturated fatty-acid level of the cells, with a slight increase in oleate but a drastic decrease in linoleate level, most probably affecting membrane fluidity. After knocking down OD expression in PCF, the linoleate content was notably reduced, whereas that of oleate drastically increased, maintaining the total unsaturated fatty-acid level unchanged. Interestingly, the growth phenotype of the RNAi-induced cells was similar to that found for thiastearate-treated trypanosomes, with the former cells growing twofold slower than the latter ones, indicating that the linoleate content itsel