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We expand upon prior work (Gibbons et al., 2012) relating childhood stressor effects, particularly harsh childhood environments, to risky behavior and ultimately physical health by adding longer-term outcomes – deoxyribonucleic acid (DNA) methylation-based measures of accelerated aging (DNAm-aging). Further, following work on the effects of early exposure to danger (McLaughlin et al., 2014), we also identify an additional pathway from harsh childhood environments to DNAm-aging that we label the danger/FKBP5 pathway, which includes early exposure to dangerous community conditions that are thought to impact glucocorticoid regulation and pro-inflammatory mechanisms. Because different DNAm-aging indices provide different windows on accelerated aging, we contrast effects on early indices of DNAm-aging based on chronological age with later indices that focused on predicting biological outcomes. We utilize data from Family and Community Health Study participants (N = 449) from age 10 to 29. We find that harshness influences parenting, which, in turn, influences accelerated DNAm-aging through the risky cognitions and substance use (i.e., behavioral) pathway outlined by Gibbons et al. (2012). Harshness is also associated with increased exposure to threat/danger, which, in turn, leads to accelerated DNAm-aging through effects on FKBP5 activity and enhanced pro-inflammatory tendencies (i.e., the danger/FKBP5 pathway).
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Identifying the mechanisms linking early experiences, genetic risk factors, and their interaction with later health consequences is central to the development of preventive interventions and identifying potential boundary conditions for their efficacy. In the current investigation of 412 African American adolescents followed across a 20-year period, we examined change in body mass index (BMI) across adolescence as one possible mechanism linking childhood adversity and adult health. We found associations of childhood adversity with objective indicators of young adult health, including a cardiometabolic risk index, a methylomic aging index, and a count of chronic health conditions. Childhood adversities were associated with objective indicators indirectly through their association with gains in BMI across adolescence and early adulthood. We also found evidence of an association of genetic risk with weight gain across adolescence and young adult health, as well as genetic moderation of childhood adversity's effect on gains in BMI, resulting in moderated mediation. These patterns indicated that genetic risk moderated the indirect pathways from childhood adversity to young adult health outcomes and childhood adversity moderated the indirect pathways from genetic risk to young adult health outcomes through effects on weight gain during adolescence and early adulthood.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
Parent–child relationships have long-term effects on health, particularly later inflammation and depression. We hypothesized that these effects would be mediated by later romantic partner relationships and elevated stressors in young adulthood, helping promote chronic, low grade, inflammation as well as depressive symptoms, and driving their covariation. It has been proposed recently that youth experiencing harsher parenting may also develop a stronger association between inflammation and depressive symptoms in adulthood and altered effects of stressors on outcomes. In the current investigation, we test these ideas using an 18-year longitudinal study of N = 413 African American youth that provides assessment of the parent–child relationship (at age 10), pro-inflammatory cytokine profile and depressive symptoms (at age 28), and potential mediators in early young adulthood (assessed at ages 21 and 24). As predicted, the effect of harsher parent–child relationships (age 10) on pro-inflammatory state and increased depressive symptoms at age 28 were fully mediated through young adult stress and romantic partner relationships. In addition, beyond these mediated effects, parent–child relationships at age 10 moderated the concurrent association between inflammation and depressive symptoms, as well as the prospective association between romantic partner relationships and inflammation, and resulted in substantially different patterns of indirect effects from young adult mediators to outcomes. The results support theorizing that the association of depression and inflammation in young adulthood is conditional on earlier parenting, and suggest incorporating this perspective into models predicting long-term health outcomes.
To develop consensus recommendations for training future clinician educators (CEs) in emergency medicine (EM).
A panel of EM education leaders was assembled from across Canada and met regularly by teleconference over the course of 1 year. Recommendations for CE training were drafted based on the panel’s experience, a literature review, and a survey of current and past EM education leaders in Canada. Feedback was sought from attendees at the Canadian Association of Emergency Physicians (CAEP) annual academic symposium. Recommendations were distributed to the society’s Academic Section for further feedback and updated by a consensus of the expert panel.
Recommendations were categorized for one of three audiences: 1) Future CEs; 2) Academic departments and divisions (AD&D) that support training to fulfill their education leadership goals; and 3) The CAEP Academic Section. Advanced medical education training is recommended for any emergency physician or resident who pursues an education leadership role. Individuals should seek out mentorship in making decisions about career opportunities and training options. AD&D should regularly perform a needs assessment of their future CE needs and identify and encourage potential individuals who fulfill education leadership roles. AD&D should develop training opportunities at their institution, provide support to complete this training, and advocate for the recognition of education scholarship in their institutional promotions process. The CAEP Academic Section should support mentorship of future CEs on a national scale.
These recommendations serve as a framework for training and supporting the next generation of Canadian EM medical educators.
Building upon various lines of research, we posited that methylation of the oxytocin receptor gene (OXTR) would mediate the effect of adult adversity on increased commitment to negative schemas and in turn the development of depression. We tested our model using structural equation modeling and longitudinal data from a sample of 100 middle-aged, African American women. The results provided strong support for the model. Analysis of the 12 CpG sites available for the promoter region of the OXTR gene identified four factors. One of these factors was related to the study variables, whereas the others were not. This factor mediated the effect of adult adversity on schemas relating to pessimism and distrust, and these schemas, in turn, mediated the impact of OXTR methylation on depression. All indirect effects were statistically significant, and they remained significant after controlling for childhood trauma, age, romantic relationship status, individual differences in cell types, and average level of genome-wide methylation. These finding suggest that epigenetic regulation of the oxytocin system may be a mechanism whereby the negative cognitions central to depression become biologically embedded.
Bimetallic nanoparticles (NPs), particularly Au/Pd and Au/Pt, have attracted extensive attention due to their wide-spread application in catalysis, optoelectronics and energy recuperation. Here we have attempted the fabrication of Au/Pt and Au/Pd bimetallic NPs by an energy-efficient eco-friendly microwave methodology. The microwave-assisted reactions enable considerably large product yields over conventional colloidal methods due to (a) almost two-fold increased reaction kinetics, (b) localized superheating at reaction sites and rapid rise of initial temperature. Au NPs (sizes 20 ± 3 nm) are fabricated in the first step followed by the reduction of [PdCl2(NH3)2] or [K2PtCl6]in tetraethylene glycol at 180 ºC for 2 min. Controlling and understanding the atomic structure and elemental distributions of these NPs are crucial for their optimized performances. So, we address the fundamental question of the most likely arrangement of Au and Pd or Pt atoms in these bimetallic NPs prepared under similar conditions by complementary characterizations using UV-Vis spectroscopy, X-ray diffraction (XRD) and transmission electron microscopy (TEM). The UV-Vis spectroscopy reveals the formation of an alloy shell. The extent of depression of the plasmon peak of Au and its blue-shift reveals substantial deposition of Pd atoms on an Au core and significant alloying in comparison to Au/Pt NPs. XRD reveals the gradual shift of the diffraction peak from the position of Au to the position of Pd or Pt with change in composition. XRD supports the formation of a thick alloy shell in these NPs. However, the TEM images reveal a very interesting result. With increase in Pt concentration, the size of the dispersed NPs decreases from 20 ± 3 nm to about 16 nm (± 1 nm) and there is evolution of a bimodal particle size distribution with small particles about 1-2 nm diameters. On the contrary, with increasing Pd concentration, the particle size of the dispersed particles increases to about 32 nm (± 1 nm). This discrepancy of particle size evolution for the two systems arises due to the differences in surface energies (Pt > Pd > Au atoms). Pt atoms tend to diffuse towards the core with the formation of Au nano-islands which eventually segregates leading to a reduction in particle size and bimodal distribution. At higher concentration of Pt, Pt and Au atoms tend to nucleate separately also contribute to the bimodal distribution. While for Au/Pd NPs, we have an Au core with an alloyed shell having higher Pd concentration. This is further supported by experimental evidence by selective etching and dissolution of Au by potassium-iodide solution. Furthermore, the Au/Pd bimetallic NPs are found to possess better catalytic activities in the reduction of 4-nitrophenol to 4-aminophenol than Au/Pt and monometallic NPs.
Two broad aims drive weed science research: improved management and improved
understanding of weed biology and ecology. In recent years, agricultural
weed research addressing these two aims has effectively split into separate
subdisciplines despite repeated calls for greater integration. Although some
excellent work is being done, agricultural weed research has developed a
very high level of repetitiveness, a preponderance of purely descriptive
studies, and has failed to clearly articulate novel hypotheses linked to
established bodies of ecological and evolutionary theory. In contrast,
invasive plant research attracts a diverse cadre of nonweed scientists using
invasions to explore broader and more integrated biological questions
grounded in theory. We propose that although studies focused on weed
management remain vitally important, agricultural weed research would
benefit from deeper theoretical justification, a broader vision, and
increased collaboration across diverse disciplines. To initiate change in
this direction, we call for more emphasis on interdisciplinary training for
weed scientists, and for focused workshops and working groups to develop
specific areas of research and promote interactions among weed scientists
and with the wider scientific community.
The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae, and orphan afterglows of gamma-ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of 5 s and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.