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Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster.
We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties.
The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature.
The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. (Disaster Med Public Health Preparedness. 2018;12:127–137)
Despite the potential of declared serving size to encourage appropriate portion size consumption, most countries including Australia have not developed clear reference guidelines for serving size. The present study evaluated variability in manufacturer-declared serving size of discretionary food and beverage products in Australia, and how declared serving size compared with the 2013 Australian Dietary Guideline (ADG) standard serve (600 kJ). Serving sizes were obtained from the Nutrition Information Panel for 4466 packaged, discretionary products in 2013 at four large supermarkets in Sydney, Australia, and categorised into fifteen categories in line with the 2013 ADG. For unique products that were sold in multiple package sizes, the percentage difference between the minimum and the maximum serving size across different package sizes was calculated. A high variation in serving size was found within the majority of food and beverage categories – for example, among 347 non-alcoholic beverages (e.g. soft drinks), the median for serving size was 250 (interquartile range (IQR) 250, 355) ml (range 100–750 ml). Declared serving size for unique products that are available in multiple package sizes also showed high variation, particularly for chocolate-based confectionery, with median percentage difference between minimum and maximum serving size of 183 (IQR 150) %. Categories with a high proportion of products that exceeded the 600 kJ ADG standard serve included cakes and muffins, pastries and desserts (≥74 % for each). High variability in declared serving size may confound interpretation and understanding of consumers interested in standardising and controlling their portion selection. Future research is needed to assess if and how standardising declared serving size might affect consumer behaviour.
This study assesses the variation between regional skeletal samples from prehistoric Easter Island on the basis of several discrete cranial traits to determine if there exists significant variation between tribal regions as described in the ethnographic record. The skeletal sample is divided into five groups representing regions of Easter Island that correspond to purported ancient tribal areas (Figure 7.1) and are compared to one another to test for statistically significant cranial trait variation with regards to specific discrete characteristics.
Due to their apparently strong genetic and low environmental factors affecting them, discrete traits are useful in population studies (Corruccini, 1974). Discrete cranial traits can be used to determine genetic distance between populations. They may also be useful in determining genetic distance within populations if political or social divisions influence gene flow between subpopulations such as tribes, clans, or kinship groups. Field observations and preliminary studies indicate that discrete traits do vary among early Easter Islanders. This study evaluates 30 cranial discrete traits and tests the hypothesis that no significant variation in cranial discrete traits exists between regional skeletal samples representing ancient Easter Island tribal areas.
The skeletons used here are from a pool of 426 individuals housed at the Sebastian Englert Museum of Anthropology, Easter Island, Chile. Much of this sample was collected by the 1981 Easter Island Anthropological Expedition, during the earlier 1979 efforts by Rapu and Gill, and subsequent field seasons, as described in the Introduction (Chapter 1) of this book (see Gill, this volume). Gill collected or supervised discrete data collection, and data were entirely rechecked on a subsequent 2002 field trip to Easter Island. All records are on file at the University of Wyoming Human Remains Repository (HRR) at the University of Wyoming, Laramie. For this study, only those remains sufficiently preserved to allow collection of discrete cranial traits, and with clear provenience are used. Also, those of unknown age at death beyond childhood are excluded. This yields a total of 106 specimens. Specimens represent the five regions of the island used for this and prior studies. These regions are North, South, Northeast, West, and Southwest (Figure 7.1).
The composition of interstellar matter is driven by environmental parameters and results from extreme interstellar medium physico-chemical conditions. Astrochemists must rely on remote observations to monitor and analyze the interstellar solids composition. They bring additional information from the study of analogues produced in the laboratory, placed in simulated space environments. Planetologists and cosmochemists access and spectroscopically examine collected extraterrestrial material in the laboratory. Diffuse interstellar medium and molecular clouds observations set constraints on the composition of organic solids that can then be compared with collected extraterrestrial materials analyses, to shed light on their possible links.
High number densities of complex oxide nanoclusters in nanostructured ferritic alloys have been shown to act as effective trapping sites for the transmutation product helium. Density functional theory has been used to investigate the evolution of the mechanical properties of oxide nanoclusters as helium concentration increases. The migration barrier and migration path of helium in the oxide has also been tested in order to make a comparison with the barriers in BCC iron and offer insight to the helium trapping mechanisms of the oxides.
Alterations of the glucocorticoid system and of hippocampal volumes have consistently been reported in patients with major depressive disorders (MDD). The aim of the present study was to investigate whether the messenger RNA (mRNA) expression of glucocorticoid inducible genes is associated with changes in the cornu ammonis (CA) and dentate gyrus subfields. Forty-three patients with MDD and 43 healthy controls were recruited and investigated with high resolution magnetic resonance imaging. Hippocampal subfields were measured using freesurfer. Measurement of whole blood mRNA expression of glucocorticoid inducible genes serum and glucocorticoid-regulated kinase 1 (SGK1), FK506 binding protein 5 (FKBP5), and glucocorticoid induced leucine zipper (GILZ) was performed. Patients with MDD had significantly smaller volumes of CA1, CA2/3, CA4/DG, and subiculum compared to healthy controls. In the regression analysis, the factor diagnosis had a significant moderating effect on the association of SGK1 and hippocampal volumes. Patients with low expression of SGK1 had significantly smaller CA2/3 and CA4/DG volumes compared to patients with high expression of SGK1 mRNA and to healthy controls with low/high expression of SGK1, respectively. Therefore, a lack of mRNA expression of glucocorticoid inducible genes in patients with MDD that seems to correspond to a blunted cortisol response is associated with smaller hippocampal CA and dentate gyrus volumes. SGK1 seems to be particularly relevant for stress-related mental disorders.
Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes.
To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia.
A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0–13 weeks and 0–39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods.
There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively.
In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.
Semantic definitions of full-scale programming languages are rarely given, despite the many potential benefits. Partly this is because the available metalanguages for expressing semantics – usually either for informal mathematics or the formal mathematics of a proof assistant – make it much harder than necessary to work with large definitions. We present a metalanguage specifically designed for this problem, and a tool, Ott, that sanity-checks such definitions and compiles them into proof assistant code for Coq, HOL, and Isabelle/HOL, together with code for production-quality typesetting, and OCaml boilerplate. The main innovations are (1) metalanguage design to make definitions concise, and easy to read and edit; (2) an expressive but intuitive metalanguage for specifying binding structures; and (3) compilation to proof assistant code. This has been tested in substantial case studies, including modular specifications of calculi from the TAPL text, a Lightweight Java with Java JSR 277/294 module system proposals, and a large fragment of OCaml (OCamllight, 310 rules), with mechanised proofs of various soundness results. Our aim with this work is to enable a phase change: making it feasible to work routinely, without heroic effort, with rigorous semantic definitions of realistic languages.
To develop policy and public health recommendations for implementation at all levels by individuals and organisations working in, or related to, the field of breast-feeding promotion in developed country settings, where breast-feeding rates remain low.
Two research phases, comprising (i) an assessment of the formal evidence base in developed country settings and (ii) a consultation with UK-based practitioners, service managers and commissioners, and representatives of service users. The evidence base included three systematic reviews and an Evidence Briefing. One hundred and ten studies evaluating an intervention in developed country settings were assessed for quality and awarded an overall quality rating. Studies with a poor quality rating were excluded. The resulting seventy studies examined twenty-five types of intervention for breast-feeding promotion. These formed the basis of the second consultation phase to develop the evidence-based interventions into recommendations for practice, which comprised (i) pilot consultation, (ii) electronic consultation, (iii) fieldwork meetings and (iv) workshops. Draft findings were synthesised for two rounds of stakeholder review conducted by the National Institute for Health and Clinical Excellence.
Twenty-five recommendations emerged within three complementary and necessary categories, i.e. public health policy, mainstream clinical practice and local interventions.
The need for national policy directives was clearly identified as a priority to address many of the barriers experienced by practitioners when trying to work across sectors, organisations and professional groups. Routine implementation of the WHO/UNICEF Baby Friendly Initiative across hospital and community services was recommended as core to breast-feeding promotion in the UK. A local mix of complementary interventions is also required.
This article undertakes an empirical investigation of the determinants of voluntary adoption of the ISO 14001 environmental management system by French farmers. The adoption model incorporates the expected profitability of implementing the standard and investigates the impact of prior knowledge on the probability of adopting. Two information measures are considered: a “reported information” indicator and an “estimated knowledge” score. The probit parameter estimates reveal that, while the expected profitability of implementing the standard is a significant determinant of adoption, real and perceived prior knowledge measures play a significant but potentially counterintuitive role.
The impact of material crystallization characteristics on the switching behavior of phase change memory cells has been investigated using finite element simulation. Both a conventional vertical cell and a horizontal line cell have been analyzed, using the widely used Ge2Sb2Te5 (GST) which is a nucleation dominated material for the vertical cell, and Ag5.5In6.5Sb59Te29 (AIST) which is a growth dominated material for the horizontal cell. Nucleation and growth models were implemented for both materials. Both RESET and SET program cycles were simulated. From these simulations, it was shown that the crystallization models gave realistic results for switching voltages, currents and switching times for the two different cell types. It is found that for GST, both nucleation (at lower voltages) and growth (at higher voltages) can play an important role in the crystallization. However, for AIST, crystal growth from non-amorphized crystal regions dominated over nucleation for all program conditions. The high growth rate of AIST moreover is shown to allow much shorter SET times in the line cell compared to that of GST in the vertical cell.