Children's biobehavioral reactivity to challenge predicts DNA methylation in adolescence and emerging adulthood.

A growing body of research has documented associations between adverse childhood environments and DNA methylation, highlighting epigenetic processes as potential mechanisms through which early external contexts influence health across the life course. The present study tested a complementary hypothesis: indicators of children's early internal, biological, and behavioral responses to stressful challenges may also be linked to stable patterns of DNA methylation later in life. Children's autonomic nervous system reactivity, temperament, and mental health symptoms were prospectively assessed from infancy through early childhood, and principal components analysis (PCA) was applied to derive composites of biological and behavioral reactivity. Buccal epithelial cells were collected from participants at 15 and 18 years of age. Findings revealed an association between early life biobehavioral inhibition/disinhibition and DNA methylation across many genes. Notably, reactive, inhibited children were found to have decreased DNA methylation of the DLX5 and IGF2 genes at both time points, as compared to non-reactive, disinhibited children. Results of the present study are provisional but suggest that the gene's profile of DNA methylation may constitute a biomarker of normative or potentially pathological differences in reactivity. Overall, findings provide a foundation for future research to explore relations among epigenetic processes and differences in both individual-level biobehavioral risk and qualities of the early, external childhood environment

EVALUATION, ASSESSMENT, AND OUTCOMES IN PHARMACY EDUCATION: THE 2007 AACP INSTITUTE Finding and Using Readily Available Sources of Assessment Data

This paper provides the rationale for, examples of, and the collection and general uses of currently available, potentially underutilized academic program assessment data. Academic program assessment is essential for program improvement and accreditation, but commonly used assessment methods may not fully meet these needs. General assessment references, pharmacy education literature, and prior experiences were used to identify and discuss sources of potentially underutilized assessment data. Pre-course assessments, graded assignments, examinations, pharmacy experience evaluations, scoring rubrics, portfolios, progress testing, self-assessments, and classroom assessment techniques are potential sources of assessment data. Course evaluations and grades may also be useful. Selection should be based on need, availability, strength, and concerns. Challenges in data management may be best met through a centralized, integrated database. Careful selection of specific embedded and other assessments can be utilized to complete the development of a comprehensive, meaningful, and efficient program assessment plan

The biological embedding of early-life socioeconomic status and family adversity in children's genome-wide DNA methylation.

AimTo examine variation in child DNA methylation to assess its potential as a pathway for effects of childhood social adversity on health across the life course.Materials & methodsIn a diverse, prospective community sample of 178 kindergarten children, associations between three types of social experience and DNA methylation within buccal epithelial cells later in childhood were examined.ResultsFamily income, parental education and family psychosocial adversity each associated with increased or decreased DNA methylation (488, 354 and 102 sites, respectively) within a unique set of genomic CpG sites. Gene ontology analyses pointed to genes serving immune and developmental regulation functions.ConclusionFindings provided support for DNA methylation as a biomarker linking early-life social experiences with later life health in humans

Incorporating Inductances in Tissue-Scale Models of Cardiac Electrophysiology

In standard models of cardiac electrophysiology, including the bidomain and monodomain models, local perturbations can propagate at infinite speed. We address this unrealistic property by developing a hyperbolic bidomain model that is based on a generalization of Ohm's law with a Cattaneo-type model for the fluxes. Further, we obtain a hyperbolic monodomain model in the case that the intracellular and extracellular conductivity tensors have the same anisotropy ratio. In one spatial dimension, the hyperbolic monodomain model is equivalent to a cable model that includes axial inductances, and the relaxation times of the Cattaneo fluxes are strictly related to these inductances. A purely linear analysis shows that the inductances are negligible, but models of cardiac electrophysiology are highly nonlinear, and linear predictions may not capture the fully nonlinear dynamics. In fact, contrary to the linear analysis, we show that for simple nonlinear ionic models, an increase in conduction velocity is obtained for small and moderate values of the relaxation time. A similar behavior is also demonstrated with biophysically detailed ionic models. Using the Fenton-Karma model along with a low-order finite element spatial discretization, we numerically analyze differences between the standard monodomain model and the hyperbolic monodomain model. In a simple benchmark test, we show that the propagation of the action potential is strongly influenced by the alignment of the fibers with respect to the mesh in both the parabolic and hyperbolic models when using relatively coarse spatial discretizations. Accurate predictions of the conduction velocity require computational mesh spacings on the order of a single cardiac cell. We also compare the two formulations in the case of spiral break up and atrial fibrillation in an anatomically detailed model of the left atrium, and [...].Comment: 20 pages, 12 figure

The Kago low-sulfidation gold and silver deposit: a peripheral mineralisation to the Nansatsu high-sulfidation system, southern Kyushu, Japan

The Kago deposit is a small deposit located at the southern tip of the Satsuma Peninsula of Southern Kyushu, Japan. It lies proximal to the well-known Nansatsu-type mineralisation province dominated by high-sulfidation type epithermal deposits. The deposit was heavily mined in the 18 th Century, largely for its relatively higher gold compared to that of surrounding and regional deposits. The Kago deposit is a typical low-sulfidation deposit, characterised by adularia-quartz veins, composed of electrum, Ag-tetrahedrite, polybasite, chalcopyrite and pyrite. Based on mine records, the grade ranged from 4.1 to 13.3 g/t Au and 2.6–6.6 g/t Ag. Alteration grades from low to high temperature argillic into a propylitic zone at the extremes of the vein exposures. Carbonate is absent. Fluid inclusion microthermometry reveals a typical temperature range of 220–240 °C with salinity of 0.7–2.6 NaCl eq. wt%. Electrum from high-grade ore ranges from 66 to 69 wt% Au. 40Ar/39Ar age dating of adularia bearing colloform/crustiform and brecciated veins, suggests a mineralisation event from 4.23 to 4.0 Ma. δ18O of veined and silicified quartz ranges from +4.0 to +18.4‰. δ18OH2O of fluids in equilibrium with quartz, in the dominant range of measured fluid inclusion temperatures, ranges from −6.5‰ to −0.2‰. δ34S of pyrite has a narrow range from −1.8 to 2.7‰. The deposit lies at the northern extent of the classic Nansatsu high-sulfidation epithermal area, in which a number of silicified bodies punctuate the region in a roughly semi-circular shape. The Kago deposit lies within the principle mineralisation age range of the high-sulfidation deposits, which range from 5.5 to 3.7 Ma. The structural displacement of the Kago deposit from the Nansatsu mineralisation and the differing host rocks has greatly influenced alteration, ore and rock-water interaction of the ore depositing fluids. Here we seek to establish the relationship that this extended mineral province has between the differing styles of mineralisation

Syn-sedimentary to diagenetic Cu ± Co mineralization in Mesoproterozoic pyritic shale driven by magmatic-hydrothermal activity on the edge of the Great Falls tectonic zone – Black Butte, Helena Embayment, Belt-Purcell Basin, USA: Evidence from sulfide Re-Os isotope geochemistry

The ca. 1,500 to 1,325 Ma Mesoproterozoic Belt-Purcell Basin is an exceptionally preserved archive of Mesoproterozoic Earth and its paleo-environmental conditions. The Belt-Purcell Basin is also host to world-class base metal sediment-hosted mineralization produced in a variety of settings from the rift stage of basin evolution through to the subsequent influence of East Kootenay and Grenvillian orogenies. The mineral potential of this basin has not been fully realized yet. New rhenium-osmium (Re-Os) data presented here for chalcopyrite, pyrite and black shale contribute to refine a robust genetic model for the origin of the Black Butte copper ± cobalt ± silver (Cu ± Co ± Ag) deposit hosted by the ca. >1,475 Ma Newland Formation in the Helena Embayment of the Belt-Purcell Basin in Montana, USA. Chalcopyrite Re-Os data yield an isochron age (1,488 ± 34 Ma, unradiogenic initial 187Os/188 Os composition Osi-chalcopyrite = 0.13 ± 0.11) that overlaps with the geological age of the Newland Formation. Further, the Re-Os data of syn-sedimentary to diagenetic massive pyrite yield evidence of resetting with an isochron age (1,358 ± 42 Ma) coincident with the timing of the East Kootenay Orogeny. The unradiogenic Osi-chalcopyrite at ca. 1,488 Ma (0.13 ± 0.11) argues for derivation of Os from a magmatic source with a 187Os/188 Os isotopic composition inherited from the upper mantle in the Mesoproterozoic (Osmantle 1,475 Ma= 0.12 ± 0.02). The unradiogenic Osi-chalcopyrite also suggests limited contamination from a continental crustal source. This source of Os and our new sulfur isotopic signatures of chalcopyrite [–4.1 to +2.1 ‰ - VCDT] implies a dominantly magmatic source for metals. We integrate our new results and previously published geological and geochemical evidence to conceptualize a genetic model in which Cu and metals were largely contributed by moderate-temperature, reduced magmatic-hydrothermal fluids carrying reduced sulfur species with a magmatic origin and flowing as highly metalliferous fluids within the shale sequence. A subsidiary derivation of metals during thermally forced shale diagenesis is possible. Chalcopyrite mineralization replaced locally massive syn-3 sedimentary to diagenetic pyrite units close to the sediment-water interface, i.e., an ideal locus where magmatic-hydrothermal fluids could cool and the solubility of chalcopyrite would fall. We suggest that Cu mineralization was coeval with the timing of an enhanced thermal gradient in the Helena Embayment triggered until ca. 1,455 Ma by tholeiitic dike swarm that intruded into Archean basement rocks and intersected the NE–SW-trending Great Falls Tectonic Zone

Ambient synthesis of nanomaterials by in situ heterogeneous metal/ligand reactions

Coordination polymers are ideal synthons in creating high aspect ratio nanostructures, however, conventional synthetic methods are often restricted to batch-wise and costly processes. Herein, we demonstrate a non-traditional, frugal approach to synthesize 1D coordination polymers by in situ etching of zerovalent metal particle precursors. This procedure is denoted as the heterogeneous metal/ligand reaction and was demonstrated on Group 13 metals as a proof of concept. Simple carboxylic acids supply the etchant protons and ligands for metal ions (conjugate base) in a 1 : 1 ratio. This scalable reaction produces a 1D polymer that assembles into high-aspect ratio 'nanobeams'. We demonstrate control over crystal structure and morphology by tuning the: (i) metal center, (ii) stoichiometry and (iii) structure of the ligands. This work presents a general scalable method for continuous, heat free and water-based coordination polymer synthesis

Risk of neuropsychiatric and cardiovascular adverse events following treatment with varenicline and nicotine replacement therapy in the UK Clinical Practice Research Datalink:a case-crossover study

BACKGROUND AND AIMS: Varenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care.DESIGN: Case crossover study.SETTING: UK based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality datasets.PARTICIPANTS: Adult smokers (n=?) observed in periods when exposed and not exposed to either varenicline or NRT.MEASUREMENTS: Main outcomes included suicide, self-harm, myocardial infarction (MI), all-cause death and cause-specific death (MI, chronic obstructive pulmonary disease (COPD)). In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure in the risk period (90 days prior to the event) with the chance of exposure in an earlier single reference period (91-180 days prior to the event) or multiple 90-day reference periods to increase statistical power.FINDINGS: In the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, whilst NRT was associated with MI (Odds ratio (OR) 1.40, 95% Confidence interval (CI) 1.18-1.67). Using multiple reference periods, varenicline was associated with an increased risk of self-harm (OR 1.32, 95% CI 1.12-1.56) and suicide (OR 3.56, 95% CI 1.32-9.60) but a reduction in all-cause death (OR 0.75, 95% CI 0.61-0.93). NRT was associated with MI (OR 1.54, 95% CI 1.36-1.74), self-harm (OR 1.30, 95% CI 1.18-1.44), and deaths from MI (OR 1.53, 95% CI 1.11-2.10), COPD (OR 1.33, 95% CI 1.14-1.56) and all causes (OR 1.28, 95% CI 1.18-1.40) when using multiple reference periods.CONCLUSIONS: There appear to be positive associations between 1) nicotine replacement therapy (NRT) and myocardial infarction, death, and risk of self-harm and 2) varenicline and increased risk of self-harm and suicide, as well as a negative association between varenicline and all-cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (NRT is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self-harm).</p

Diatremes act as fluid conduits for Zn-Pb mineralization in the SW Irish Ore field

Irish-type mineralization is commonly attributed to fault-controlled mixing of a seawater-derived, sulfur-rich fluid and basement-derived, metal-rich fluid. However, maar-diatreme volcanoes discovered in close spatial and temporal association with Zn-Pb mineralization at Stonepark in the Limerick basin (southwest Ireland) bring a new dimension to established geologic models and may increase the deposit-scale prospectivity in one of the world’s greatest Zn-Pb districts. Stonepark exhibits many incidences of dolomitic black matrix breccias with associated Zn-Pb mineralization, the latter typically occurring within 150 m of the diatremes. Highly negative δ34S pyrite values within country rock-dominated black matrix breccias (–12 to –34‰) are consistent with sulfide precipitation from bacteriogenic sulfur reduction in seawater-derived brines. However, δ34S values of Zn-Pb sulfides replacing black matrix breccias (–10 to 1‰) reflect multiple sulfur sources. Diatreme emplacement both greatly enhanced country rock fracture permeability and produced conduits that are filled with porous volcaniclastic material and extend down to basement rock types. Our δ34S data suggest that diatremes provide more efficient fluid pathways for basement-derived fluids. The diatremes introduce another potential sulfur source and facilitate a greater input of metal-rich basement-derived hydrothermal fluid into the system compared to other Irish-type deposits such as Navan and Lisheen, evidenced by Stonepark’s more positive modal δ34S value of –4‰. Irish-type deposits are traditionally thought to form in association with extensional basement faults and are considered unrelated to extensive Carboniferous magmatism. Our results indicate that a direct link exists between diatreme volcanism and Zn-Pb mineralization at Limerick, prompting a reevaluation of the traditional Irish-type ore formation model, in regions where mineralization is spatially associated with volcanic pipes.Natural Environment Research Council (IP-1397-1113); SUERC; Teck Ireland Ltd