Generation and quality control of lipidomics data for the alzheimers disease neuroimaging initiative cohort.

Alzheimers disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insights in the disease etiology. We report here an untargeted lipidomics of serum specimens of 806 subjects within the ADNI1 cohort (188 AD, 392 mild cognitive impairment and 226 cognitively normal subjects) along with 83 quality control samples. Lipids were detected and measured using an ultra-high-performance liquid chromatography quadruple/time-of-flight mass spectrometry (UHPLC-QTOF MS) instrument operated in both negative and positive electrospray ionization modes. The dataset includes a total 513 unique lipid species out of which 341 are known lipids. For over 95% of the detected lipids, a relative standard deviation of better than 20% was achieved in the quality control samples, indicating high technical reproducibility. Association modeling of this dataset and available clinical, metabolomics and drug-use data will provide novel insights into the AD etiology. These datasets are available at the ADNI repository at http://adni.loni.usc.edu/

Examining the importance of Aberdeenshire (UK) coastal waters for North Sea bottlenose dolphins (Tursiops truncatus)

Using land- and vessel-based surveys, data on the relative abundance, distribution and habitat use of bottlenose dolphins (Tursiops truncatus) in Aberdeenshire waters were collected between 1999 and 2001. Bottlenose dolphins were present throughout the year, with peak abundance during the months of March to May. The occurrence of calves was seasonal, with the proportion of calves highest during the spring months. Foraging behaviour was recorded mainly in the vicinity of Aberdeen harbour. Dolphins photographed in Aberdeenshire waters were successfully matched and confirmed as Moray Firth animals. The results of the present study suggest that Moray Firth bottlenose dolphins utilize Aberdeenshire waters more frequently than previously reported. Aberdeen harbour is apparently an important feeding area, and Aberdeenshire waters are regularly used by mother-calf pairs. This has important management implications since this area of coastline does not currently form part of the designated Special Area of Conservation (SAC) for this population

Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers : a randomized study

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are renoprotective but both may increase serum potassium concentrations in patients with chronic kidney disease (CKD). The proportion of affected patients, the optimum follow-up period and whether there are differences between drugs in the development of this complication remain to be scertained. Methods: In a randomized, double-blind, phase IV, controlled, crossover study we recruited 30 patients with stage 3 CKD under restrictive eligibility criteria and strict dietary control. With the exception of withdrawals, each patient was treated with olmesartan and enalapril separately for 3 months each, with a 1-week wash-out period between treatments. Patients were clinically assessed on 10 occasions via measurements of serum and urine samples. We used the Cochran-Mantel-Haenszel statistics for comparison of categorical data between groups. Comparisons were also made using independent two-sample t-tests and Welch's t-test. Analysis of variance (ANOVA) was performed when necessary. We used either a Mann-Whitney or Kruskal-Wallis test if the distribution was not normal or the variance not homogeneous. Results: Enalapril and olmesartan increased serum potassium levels similarly (0.3 mmol/L and 0.24 mmol/L respectively). The percentage of patients presenting hyperkalemia higher than 5 mmol/L did not differ between treatments: 37% for olmesartan and 40% for enalapril. The mean e-GFR ranged 46.3 to 48.59 ml/mint/1.73 m2 in those treated with olmesartan and 46.8 to 48.3 ml/mint/1.73 m2 in those with enalapril and remained unchanged at the end of the study. The decreases in microalbuminuria were also similar (23% in olmesartan and 29% in enalapril patients) in the 4 weeks time point. The percentage of patients presenting hyperkalemia, even after a two month period, did not differ between treatments. There were no appreciable changes in sodium and potassium urinary excretion. Conclusions: Disturbances in potassium balance upon treatment with either olmesartan or enalapril are frequent and without differences between groups. The follow-up of these patients should include control of potassium levels, at least after the first week and the first and second month after initiating treatment

TLR-4 ligation of dendritic cells is sufficient to drive pathogenic T cell function in experimental autoimmune encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>Experimental autoimmune encephalomyelitis (EAE) depends on the initial activation of CD4⁺ T cells responsive to myelin autoantigens. The key antigen presenting cell (APC) population that drives the activation of naïve T cells most efficiently is the dendritic cell (DC). As such, we should be able to trigger EAE by transfer of DC that can present the relevant autoantigen(s). Despite some sporadic reports, however, models of DC-driven EAE have not been widely adopted. We sought to test the feasibility of this approach and whether activation of the DC by toll-like receptor (TLR)-4 ligation was a sufficient stimulus to drive EAE.</p> <p>Findings</p> <p>Host mice were seeded with myelin basic protein (MBP)-reactive CD4+ T cells and then were injected with DC that could present the relevant MBP peptide which had been exposed to lipopolysaccharide as a TLR-4 agonist. We found that this approach induced robust clinical signs of EAE.</p> <p>Conclusions</p> <p>DC are sufficient as APC to effectively drive the differentiation of naïve myelin-responsive T cells into autoaggressive effector T cells. TLR-4-stimulation can activate the DC sufficiently to deliver the signals required to drive the pathogenic function of the T cell. These models will allow the dissection of the molecular requirements of the initial DC-T cell interaction in the lymphoid organs that ultimately leads to autoimmune pathology in the central nervous system.</p

Pacing and Decision Making in Sport and Exercise: The Roles of Perception and Action in the Regulation of Exercise Intensity

In pursuit of optimal performance, athletes and physical exercisers alike have to make decisions about how and when to invest their energy. The process of pacing has been associated with the goal-directed regulation of exercise intensity across an exercise bout. The current review explores divergent views on understanding underlying mechanisms of decision making in pacing. Current pacing literature provides a wide range of aspects that might be involved in the determination of an athlete's pacing strategy, but lacks in explaining how perception and action are coupled in establishing behaviour. In contrast, decision-making literature rooted in the understanding that perception and action are coupled provides refreshing perspectives on explaining the mechanisms that underlie natural interactive behaviour. Contrary to the assumption of behaviour that is managed by a higher-order governor that passively constructs internal representations of the world, an ecological approach is considered. According to this approach, knowledge is rooted in the direct experience of meaningful environmental objects and events in individual environmental processes. To assist a neuropsychological explanation of decision making in exercise regulation, the relevance of the affordance competition hypothesis is explored. By considering pacing as a behavioural expression of continuous decision making, new insights on underlying mechanisms in pacing and optimal performance can be developed. © 2014 Springer International Publishing Switzerland

The stranding anomaly as population indicator: the case of Harbour Porpoise <i>Phocoena phocoena</i> in North-Western Europe

Ecological indicators for monitoring strategies are expected to combine three major characteristics: ecological significance, statistical credibility, and cost-effectiveness. Strategies based on stranding networks rank highly in cost-effectiveness, but their ecological significance and statistical credibility are disputed. Our present goal is to improve the value of stranding data as population indicator as part of monitoring strategies by constructing the spatial and temporal null hypothesis for strandings. The null hypothesis is defined as: small cetacean distribution and mortality are uniform in space and constant in time. We used a drift model to map stranding probabilities and predict stranding patterns of cetacean carcasses under H-0 across the North Sea, the Channel and the Bay of Biscay, for the period 1990-2009. As the most common cetacean occurring in this area, we chose the harbour porpoise <i>Phocoena phocoena</i> for our modelling. The difference between these strandings expected under H-0 and observed strandings is defined as the stranding anomaly. It constituted the stranding data series corrected for drift conditions. Seasonal decomposition of stranding anomaly suggested that drift conditions did not explain observed seasonal variations of porpoise strandings. Long-term stranding anomalies increased first in the southern North Sea, the Channel and Bay of Biscay coasts, and finally the eastern North Sea. The hypothesis of changes in porpoise distribution was consistent with local visual surveys, mostly SCANS surveys (1994 and 2005). This new indicator could be applied to cetacean populations across the world and more widely to marine megafauna

Evidence for rangewide panmixia despite multiple barriers to dispersal in a marine mussel

Oceanographic features shape the distributional and genetic patterns of marine species by interrupting or promoting connections among populations. Although general patterns commonly arise, distributional ranges and genetic structure are species-specific and do not always comply with the expected trends. By applying a multimarker genetic approach combined with Lagrangian particle simulations (LPS) we tested the hypothesis that oceanographic features along northeastern Atlantic and Mediterranean shores influence dispersal potential and genetic structure of the intertidal mussel Perna perna. Additionally, by performing environmental niche modelling we assessed the potential and realized niche of P. perna along its entire native distributional range and the environmental factors that best explain its realized distribution. Perna perna showed evidence of panmixia across > 4,000 km despite several oceanographic breaking points detected by LPS. This is probably the result of a combination of life history traits, continuous habitat availability and stepping-stone dynamics. Moreover, the niche modelling framework depicted minimum sea surface temperatures (SST) as the major factor shaping P. perna distributional range limits along its native areas. Forthcoming warming SST is expected to further change these limits and allow the species to expand its range polewards though this may be accompanied by retreat from warmer areas.Fundacao para a Ciencia e Tecnologia (FCT-MEC, Portugal) [UID/Multi/04326/2013, IF/01413/2014/CP1217/CT0004]; South African Research Chairs Initiative (SARChI) of the Department of Science and Technology; National Research Foundation; South African National Research Foundation (NRF); Portuguese Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BPD/85040/2012, SFRH/BPD/111003/2015]info:eu-repo/semantics/publishedVersio

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

Targeting condom distribution at high risk places increases condom utilization-evidence from an intervention study in Livingstone, Zambia

Background: The PLACE-method presumes that targeting HIV preventive activities at high risk places is effective in settings with major epidemics. Livingstone, Zambia, has a major HIV epidemic despite many preventive efforts in the city. A baseline survey conducted in 2005 in places where people meet new sexual partners found high partner turnover and unprotected sex to be common among guests. In addition, there were major gaps in on-site condom availability. This study aimed to assess the impact of a condom distribution and peer education intervention targeting places where people meet new sexual partners on condom use and sexual risk taking among people socializing there. Methods: The 2005 baseline survey assessed the presence of HIV preventive activities and sexual risk taking in places where people meet new sexual partners in Livingstone. One township was selected for a non-randomised intervention study on condom distribution and peer education in high risk venues in 2009. The presence of HIV preventive activities in the venues during the intervention was monitored by an external person. The intervention was evaluated after one year with a follow-up survey in the intervention township and a comparison township. In addition, qualitative interviews and focus group discussions were conducted. Results: Young people between 17-32 years of age were recruited as peer educators, and 40% were females. Out of 72 persons trained before the intervention, 38 quit, and another 11 had to be recruited. The percentage of venues where condoms were reported to always be available at least doubled in both townships, but was significantly higher in the intervention vs. the control venues in both surveys (84% vs. 33% in the follow-up). There was a reduction in reported sexual risk taking among guests socializing in the venues in both areas, but reporting of recent condom use increased more among people interviewed in the intervention (57% to 84%) than in the control community (55% to 68%). Conclusions: It is likely that the substantial increase in reported condom use in the intervention venues was partially due to the condom distribution and peer education intervention targeting these places. However, substantial changes were observed also in the comparison community over the five year period, and this indicates that major changes had occurred in overall risk taking among people socializing in venues where people meet new sexual partners in Livingstone

Distribution of variation over populations

Understanding the significance of the distribution of genetic or phenotypic variation over populations is one of the central concerns of population genetic and ecological research. The import of the research decisively depends on the measures that are applied to assess the amount of variation residing within and between populations. Common approaches can be classified under two perspectives: differentiation and apportionment. While the former focuses on differences (distances) in trait distribution between populations, the latter considers the division of the overall trait variation among populations. Particularly when multiple populations are studied, the apportionment perspective is usually given preference (via FST/GST indices), even though the other perspective is also relevant. The differences between the two perspectives as well as their joint conceptual basis can be exposed by referring them to the association between trait states and population affiliations. It is demonstrated that the two directions, association of population affiliation with trait state and of trait state with population affiliation, reflect the differentiation and the apportionment perspective, respectively. When combining both perspectives and applying the suggested measure of association, new and efficient methods of analysis result, as is outlined for population genetic processes. In conclusion, the association approach to an analysis of the distribution of trait variation over populations resolves problems that are frequently encountered with the apportionment perspective and its commonly applied measures in both population genetics and ecology, suggesting new and more comprehensive methods of analysis that include patterns of differentiation and apportionment