Variscan sourcing of Westphalian (Pennsylvanian) sandstones in the Canobie Coalfield, UK

The zircon age spectrum in a sample from the Canonbie Bridge Sandstone Formation (Asturian) of southern Scotland contains two main peaks. One is Early Carboniferous in age (348– 318 Ma), and corresponds to the age of igneous activity during the Variscan Orogeny. The other is of late Neoproterozoic to early Cambrian age (693–523 Ma), corresponding to the Cadomian. Together, these two groups comprise 70 % of the zircon population. The presence of these two peaks shows unequivocally that a significant proportion of the sediment was derived from the Variscides of western or central Europe. The zircon population also contains a range of older Proterozoic zircons and a small Devonian component. These could have been derived from the Variscides, but it is possible that some were locally derived through recycling of northerly derived sandstones of Devonian–Carboniferous age. The zircon age data confirm previous suggestions of Variscide sourcing to the Canonbie area, made on the basis of petrographical, heavy mineral and palaeocurrent evidence, and extend the known northward distribution of Variscan-derived Westphalian sediment in the UK

Principles of Good Practice for Budget Impact Analysis: Report of the ISPOR Task Force on Good Research Practices—Budget Impact Analysis

AbstractObjectiveThere is growing recognition that a comprehensive economic assessment of a new health-care intervention at the time of launch requires both a cost-effectiveness analysis (CEA) and a budget impact analysis (BIA). National regulatory agencies such as the National Institute for Health and Clinical Excellence in England and Wales and the Pharmaceutical Benefits Advisory Committee in Australia, as well as managed care organizations in the United States, now require that companies submit estimates of both the cost-effectiveness and the likely impact of the new health-care interventions on national, regional, or local health plan budgets. Although standard methods for performing and presenting the results of CEAs are well accepted, the same progress has not been made for BIAs. The objective of this report is to present guidance on methodologies for those undertaking such analyses or for those reviewing the results of such analyses.MethodsThe Task Force was appointed with the advice and consent of the Board of Directors of ISPOR. Members were experienced developers or users of budget impact models, worked in academia, industry, and as advisors to governments, and came from several countries in North America, Oceana, Asia, and Europe. The Task Force met to develop core assumptions and an outline before preparing a draft report. They solicited comments on the outline and two drafts from a core group of external reviewers and more broadly from the membership of ISPOR at two ISPOR meetings and via the ISPOR web site.ResultsThe Task Force recommends that the budget impact of a new health technology should consider the perspective of the specific health-care decision-maker. As such, the BIA should be performed using data that reflect, for a specific health condition, the size and characteristics of the population, the current and new treatment mix, the efficacy and safety of the new and current treatments, and the resourceuse and costs for the treatments and symptoms as would apply to the population of interest. The Task Force recommends that budget impact analyses be generated as a series of scenario analyses in the same manner that sensitivity analyses would be provided for CEAs. In particular, the input values for the calculation and the specific cost outcomes presented (a scenario) should be specific to a particular decision-maker's population and information needs. Sensitivity analysis should also be in the form of alternative scenarios chosen from the perspective of the decision-maker. The primary data sources for estimating the budget impact should be published clinical trial estimates and comparator studies for efficacy and safety of current and new technologies as well as, where possible, the decision-maker's own population for the other parameter estimates. Suggested default data sources also are recommended. These include the use of published data, well-recognized local or national statistical information and in special circumstances, expert opinion. Finally, the Task Force recommends that the analyst use the simplest design that will generate credible and transparent estimates. If a health condition model is needed for the BIA, it should reflect health outcomes and their related costs in the total affected population for each year after the new intervention is introduced into clinical practice. The model should be consistent with that used for the CEA with regard to clinical and economic assumptions.ConclusionThe BIA is important, along with the CEA, as part of a comprehensive economic evaluation of a new health technology. We propose a framework for creating budget impact models, guidance about the acquisition and use of data to make budget projections and a common reporting format that will promote standardization and transparency. Adherence to these proposed good research practice principles would not necessarily supersede jurisdiction-specific budget impact guidelines, but may support and enhance localrecommendations or serve as a starting point for payers wishing to promulgate methodology guidelines

An investigation of the impact of young children's self-knowledge of trustworthiness on school adjustment: a test of the realistic self-knowledge and positive illusion models

The study aimed to examine the relationship between self-knowledge of trustworthiness and young children’s school adjustment. One hundred and seventy-three (84 male and 89 female) children from school years 1 and 2 in the United Kingdom (mean age 6 years 2 months) were tested twice over one year. Children’s trustworthiness was assessed using: (a) self-report at Time 1 and Time 2, (b) peers’ reports at Time 1 and Time 2, and (c) teacher-reports at Time 2. School adjustment was assessed by child-rated school-liking and the Short-Form Teacher Rating Scale of School Adjustment. Longitudinal quadratic relationships were found between school adjustment and children’s self-knowledge, using peer-reported trustworthiness as a reference: more accurate self-knowledge of trustworthiness predicted increases in school adjustment. Comparable concurrent quadratic relationships were found between teacher-rated school adjustment and children’s self-knowledge, using teacher-reported trustworthiness as a reference, at Time 2. The findings support the conclusion that young children’s psychosocial adjustment is best accounted for by the realistic self-knowledge model (Colvin & Block, 1994)

The early childhood generalized trust belief scale

The study was designed to develop and evaluate the Early Childhood Generalized Trust Belief Scale (ECGTBS) as a method of assessing 5-to-8-year-olds’ generalized trust. Two hundred and eleven (103 male and 108 female) children (mean age 6 years and 2 months at Time 1) completed the ECGTBS twice over a year. A subsample of participants completed the ECGTBS after two weeks to assess the scale’s test-retest reliability. Exploratory and confirmatory factor analyses confirmed that the ECGTBS assessed the expected three factors: reliability, emotional trust, and honesty with item-pairs loading most strongly on their corresponding factor. However, the ECGTBS demonstrated low to modest internal consistency and test-retest reliability which indicates a need for further development of this instrument. As evidence for the convergent validity of the ECGTBS, the reliability and emotional trust items were associated with the children’s trust in classmates at Time 2. Concurrent asymmetric quadratic relationships indicated the importance of midrange generalized trust. Specifically, children with very high generalized trust experienced greater loneliness and children with very low generalized trust had fewer friendships than children with midrange trust

Young children's interpersonal trust consistency as a predictor of future school adjustment

Young children’s interpersonal trust consistency was examined as a predictor of future school adjustment. One hundred and ninety two (95 male and 97 female, M age = 6 years 2 months, SD age = 6 months) children from school years 1 and 2 in the United Kingdom were tested twice over one-year. Children completed measures of peer trust and school adjustment and teachers completed the Short-Form Teacher Rating Scale of School Adjustment. Longitudinal quadratic relationships emerged between consistency of children’s peer trust beliefs and peer-reported trustworthiness and school adjustment and these varied according to social group, facet of trust, and indictor of school adjustment. The findings support the conclusion that interpersonal trust consistency, especially for secret-keeping, predicts aspects of young children’s school adjustment

Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase

Little is known about quality control of proteins that aberrantly or persistently engage the endoplasmic reticulum (ER)-localized translocon en route to membrane localization or the secretory pathway. Hrd1 and Doa10, the primary ubiquitin ligases that function in ER-associated degradation (ERAD) in yeast, target distinct subsets of misfolded or otherwise abnormal proteins based primarily on degradation signal (degron) location. We report the surprising observation that fusing Deg1, a cytoplasmic degron normally recognized by Doa10, to the Sec62 membrane protein rendered the protein a Hrd1 substrate. Hrd1-dependent degradation occurred when Deg1-Sec62 aberrantly engaged the Sec61 translocon channel and underwent topological rearrangement. Mutations that prevent translocon engagement caused a reversion to Doa10-dependent degradation. Similarly, a variant of apolipoprotein B, a protein known to be cotranslocationally targeted for proteasomal degradation, was also a Hrd1 substrate. Hrd1 therefore likely plays a general role in targeting proteins that persistently associate with and potentially obstruct the translocon

Dichotomy in the NRT Gene Families of Dicots and Grass Species

A large proportion of the nitrate (NO3−) acquired by plants from soil is actively transported via members of the NRT families of NO3− transporters. In Arabidopsis, the NRT1 family has eight functionally characterised members and predominantly comprises low-affinity transporters; the NRT2 family contains seven members which appear to be high-affinity transporters; and there are two NRT3 (NAR2) family members which are known to participate in high-affinity transport. A modified reciprocal best hit (RBH) approach was used to identify putative orthologues of the Arabidopsis NRT genes in the four fully sequenced grass genomes (maize, rice, sorghum, Brachypodium). We also included the poplar genome in our analysis to establish whether differences between Arabidopsis and the grasses may be generally applicable to monocots and dicots. Our analysis reveals fundamental differences between Arabidopsis and the grass species in the gene number and family structure of all three families of NRT transporters. All grass species possessed additional NRT1.1 orthologues and appear to lack NRT1.6/NRT1.7 orthologues. There is significant separation in the NRT2 phylogenetic tree between NRT2 genes from dicots and grass species. This indicates that determination of function of NRT2 genes in grass species will not be possible in cereals based simply on sequence homology to functionally characterised Arabidopsis NRT2 genes and that proper functional analysis will be required. Arabidopsis has a unique NRT3.2 gene which may be a fusion of the NRT3.1 and NRT3.2 genes present in all other species examined here. This work provides a framework for future analysis of NO3− transporters and NO3− transport in grass crop species

The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)

Preventive evidence into practice (PEP) study: implementation of guidelines to prevent primary vascular disease in general practice protocol for a cluster randomised controlled trial

There are significant gaps in the implementation and uptake of evidence-based guideline recommendations for cardiovascular disease (CVD) and diabetes in Australian general practice. This study protocol describes the methodology for a cluster randomised trial to evaluate the effectiveness of a model that aims to improve the implementation of these guidelines in Australian general practice developed by a collaboration between researchers, non-government organisations, and the profession.This study is funded by an Australian National Health and Medical Research Council (NHMRC) Partnership grant (ID 568978) together with the Australian National Heart Foundation, Royal Australian College of General Practitioners, and the BUPA Foundation. MH is supported by a NHMRC Senior Principle Research Fellowship