Consulting with young people to inform systematic reviews: an example from a review on the effects of schools on health

Background: There has been increasing interest in involving the public in systematic reviews to help ensure the review is focused on issues that are important and relevant to them. Case examples of this involvement are rare, especially for reviews focused on children and young people. Objective: This study aims to describe the process and outcome of consulting with young people in a review of the effects of school environment interventions on children and young people’s health. Young people’s perspectives were sought alongside the perspectives of teachers, policy-makers and academics to determine the scope and priorities for review. Methods: Consultations were conducted with a pre-existing group of young people brought together to advise on public health research. Their views were sought at three stages: 1) at the beginning when general views relating to the policy problem under study were elicited; 2) half-way through when views on the map of identified evidence were sought; and 3) near the end when the review results were presented and discussed. Face to face to consultation methods were used, supplemented with online social networking for young people to continue discussion. Findings: Each consultation stage helped shape the review process. For example, the first and second consultations helped researchers understand the policy problem in its current context and informed the development of inclusion criteria for priority review areas. Face to face consultation was better at engaging young people but social networking gave the review team greater flexibility to elicit further views when unanticipated issues arose needing immediate input. Conclusion: Consulting with young people alongside other stakeholders added considerable value to the review, especially in terms of helping the review team to prioritise in a relevant and meaningful way. The use of a pre-existing group facilitated engagement, but the use of social networking requires further evaluation

Mechanical robustness of HL-LHC collimator designs

Two new absorbing materials were developed as collimator inserts to fulfil the requirements of HL-LHC higher brightness beams: molybdenum-carbide graphite (MoGr) and copper-diamond (CuCD). These materials were tested under intense beam impacts at CERN HiRadMat facility in 2015, when full jaw prototypes were irradiated. Additional tests in HiRadMat were performed in 2017 on another series of material samples, including also improved grades of MoGr and CuCD, and different coating solutions. This paper summarizes the main results of the two experiments, with a main focus on the behaviour of the novel composite blocks, the metallic housing, as well as the cooling circuit. The experimental campaign confirmed the final choice for the materials and the design solutions for HL-LHC collimators, and constituted a unique chance of benchmarking numerical models. In particular, the tests validated the selection of MoGr for primary and secondary collimators, and CuCD as a valid solution for robust tertiary collimators

Wetland succession in a permafrost collapse: interactions between fire and thermokarst

To determine the influence of fire and thermokarst in a boreal landscape, we investigated peat cores within and adjacent to a permafrost collapse feature on the Tanana River Floodplain of Interior Alaska. Radioisotope dating, diatom assemblages, plant macrofossils, charcoal fragments, and carbon and nitrogen content of the peat profile indicate ~600 years of vegetation succession with a transition from a terrestrial forest to a sedge-dominated wetland over 100 years ago, and to a <i>Sphagnum</i>-dominated peatland in approximately 1970. The shift from sedge to <i>Sphagnum</i>, and a decrease in the detrended tree-ring width index of black spruce trees adjacent to the collapse coincided with an increase in the growing season temperature record from Fairbanks. This concurrent wetland succession and reduced growth of black spruce trees indicates a step-wise ecosystem-level response to a change in regional climate. In 2001, fire was observed coincident with permafrost collapse and resulted in lateral expansion of the peatland. These observations and the peat profile suggest that future warming and/or increased fire disturbance could promote permafrost degradation, peatland expansion, and increase carbon storage across this landscape; however, the development of drought conditions could reduce the success of both black spruce and <i>Sphagnum</i>, and potentially decrease the long-term ecosystem carbon storage

Self-dual Ginzburg-Landau vortices in a disk

We study the properties of the Ginzburg-Laundau model in the self-dual point for a two-dimensional finite system . By a numerical calculation we analyze the solutions of the Euler-Lagrange equations for a cylindrically symmetric ansatz. We also study the self-dual equations for this case. We find that the minimal energy configurations are not given by the Bogomol'nyi equations but by solutions to the Euler Lagrange ones. With a simple approximation scheme we reproduce the result of the numerical calculation.Comment: 8 pages, 4 figures, RevTex macro

Synthesis and Structure-Activity Relationships of Pyridoxal-6-arylazo-5'-phosphate and Phosphonate Derivatives as P2 Receptor Antagonists.

Novel analogs of the P2 receptor antagonist pyridoxal-5'-phosphate-6-phenylazo-2',4'-disulfonate (PPADS) were synthesized. Modifications were made through functional group substitution on the sulfophenyl ring and at the phosphate moiety through the inclusion of phosphonates, demonstrating that a phosphate linkage is not required for P2 receptor antagonism. Substituted 6-phenylazo and 6-naphthylazo derivatives were also evaluated. Among the 6-phenylazo derivatives, 5'-methyl, ethyl, propyl, vinyl, and allyl phosphonates were included. The compounds were tested as antagonists at turkey erythrocyte and guinea-pig taenia coli P2Y(1) receptors, in guinea-pig vas deferens and bladder P2X(1) receptors, and in ion flux experiments by using recombinant rat P2X(2) receptors expressed in Xenopus oocytes. Competitive binding assay at human P2X(1) receptors in differentiated HL-60 cell membranes was carried out by using [(35)S]ATP-?-S. A 2'-chloro-5'-sulfo analog of PPADS (C(14)H(12)O(9)N(3)ClPSNa), a vinyl phosphonate derivative (C(15)H(12)O(11)N(3)PS(2)Na(3)), and a naphthylazo derivative (C(18)H(14)O(12)N(3)PS(2)Na(2)), were particularly potent in binding to human P2X(1) receptors. The potencies of phosphate derivatives at P2Y(1) receptors were generally similar to PPADS itself, except for the p-carboxyphenylazo phosphate derivative C(15)H(13)O(8)N(3)PNa and its m-chloro analog C(15)H(12)O(8)N(3)ClPNa, which were selective for P2X vs. P2Y(1) receptors. C(15)H(12)O(8)N(3)ClPNa was very potent at rat P2X(2) receptors with an IC(50) value of 0.82 ?M. Among the phosphonate derivatives, [4-formyl-3-hydroxy-2-methyl-6-(2-chloro-5-sulfonylphenylazo)-pyrid-5-yl]methylphosphonic acid (C(14)H(12)-O(8)N(3)ClPSNa) showed high potency at P2Y(1) receptors with an IC(50) of 7.23 ?M. The corresponding 2,5-disulfonylphenyl derivative was nearly inactive at turkey erythrocyte P2Y(1) receptors, whereas at recombinant P2X(2) receptors had an IC(50) value of 1.1 ?M. An ethyl phosphonate derivative (C(15)H(15)O(11)N(3)PS(2)Na(3)), whereas inactive at turkey erythrocyte P2Y(1) receptors, was particularly potent at recombinant P2X(2) receptors

Genetic associations with learning over 100 days of practice

Cognitive performance is both heritable and sensitive to environmental inputs and sustained practice over time. However, it is currently unclear how genetic effects on cognitive performance change over the course of learning. We examine how polygenic scores (PGS) created from genome-wide association studies of educational attainment and cognitive performance are related to improvements in performance across nine cognitive tests (measuring perceptual speed, working memory, and episodic memory) administered to 131 adults (N = 51, ages = 20–31, and N = 80, ages = 65–80 years) repeatedly across 100 days. We observe that PGS associations with performance on a given task can change over the course of learning, with the specific pattern of change in associations differing across tasks. PGS correlations with pre-test to post-test scores may mask variability in how soon learning occurs over the course of practice. The associations between PGS and learning do not appear to simply reconstitute patterns of association between baseline performance and subsequent learning. Associations involving PGSs, however, were small with large confidence intervals. Intensive longitudinal research such as that described here may be of substantial value for clarifying the genetics of learning when implemented as far larger scale

Heterocyclic synthesis with nitriles: synthesis of pyrazolopyrimidine and pyrazolopyridine derivatives

The reaction of N1-substituted-5-amino-4-cyanopyrazoles with malononitrile and diethylmalonate occurs with formation of 6-substituted pyrazolo[3,4-d]pyrimidines, and pyrazolo[3,4-b]pyridines respectively. The structures of the products and conceivable mechanisms are discussed.Fundação para a Ciência e Tecnologia - SFRH/BPD/31490/2006Fundo Europeu de Desenvolvimento Regional (FEDER) - POCTI-SFA-3-68

Agonist-induced alteration in the membrane form of muscarinic cholinergic receptors

Incubation of 1321N1 human astrocytoma cells with carbachol resulted in a rapid loss of binding of [3H]N-methylscopolamine ([3H]NMS) to muscarinic cholinergic receptors measured at 4 degrees C on intact cells; loss of muscarinic receptors in lysates from the same cells measured with [3H]quinuclidinyl benzilate [( 3H]QNB) at 37 degrees C occurred at a slower rate. Upon removal of agonist from the medium, the lost [3H]NMS binding sites measured on intact cells recovered with a t1/2 of approximately 20 min, but only to the level to which [3H]QNB binding sites had been lost; no recovery of "lost" [3H]QNB binding sites occurred over the same period. Based on these data and the arguments of Galper et al. (Galper, J. B., Dziekan, L. C., O'Hara, D. S., and Smith, T. W. (1982) J. Biol. Chem. 257, 10344-10356) regarding the relative hydrophilicity of [3H]NMS versus [3H]QNB, it is proposed that carbachol induces a rapid sequestration of muscarinic receptors that is followed by a loss of these receptors from the cell. These carbachol-induced changes are accompanied by a change in the membrane form of the muscarinic receptor. Although essentially all of the muscarinic receptors from control cells co-purified with the plasma membrane fraction on sucrose density gradients, 20-35% of the muscarinic receptors from cells treated for 30 min with 100 microM carbachol migrated to a much lower sucrose density. This conversion of muscarinic receptors to a "light vesicle" form occurred with a t1/2 approximately 10 min, and reversed with a t1/2 approximately 20 min. In contrast to previous results in this cell line regarding beta-adrenergic receptors (Harden, T. K., Cotton, C. U., Waldo, G. L., Lutton, J. K., and Perkins, J. P. (1980) Science 210, 441-443), agonist binding to muscarinic receptors in the light vesicle fraction obtained from carbachol-treated cells was still regulated by GTP. One interpretation of these data is that agonists induce an internalization of muscarinic receptors with the retention of their functional interaction with a guanine nucleotide regulatory protein

Parental depression and offspring psychopathology: A Children of Twins study

Background Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. Method A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. Results In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20–1.93] and conduct disorder (CD; HR 2.27, CI 1.31–3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00–1.94). Logistic regression analysis suggested that the parental depression–offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63–3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95–6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. Conclusions The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD