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Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.
Maternal body mass index (BMI) and gestational weight gain (GWG) impacts both the mother’s and the child’s health, and epigenetic modifications have been suggested to mediate some of these effects in offspring. This systematic review aimed to summarize the current literature on associations between maternal BMI and GWG and epigenetic marks. We performed systematic searches in PubMed and EMBASE and manual searches of reference lists. We included 49 studies exploring the association between maternal BMI and/or GWG and DNA methylation or miRNA; 7 performed in maternal tissues, 13 in placental tissue and 38 in different offspring tissues. The most consistent findings were reported for the relationship between maternal BMI, in particular pre-pregnant BMI, and expression of miRNA Let-7d in both maternal blood and placental tissue, methylation of the gene HIF3A in umbilical cord blood and umbilical tissue, and with expression in the miR-210 target gene, BDNF in placental tissue and cord blood. Correspondingly, methylation of BDNF was also found in placental tissue and cord blood. The current evidence suggests that maternal BMI is associated with some epigenetic signatures in the mother, the placenta and her offspring, which could indicate that some of the effects proposed by the Developmental Origins of Health and Disease-hypothesis may be mediated by epigenetic marks. In conclusion, there is a need for large, well-designed studies and meta-analyses that can clarify the relationship between BMI, GWG and epigenetic changes.
In Chapter 8, Brenda Gunn looks to Canada as an example when she provides an analysis of how states have obligations to ensure the protection and promotion of Indigenous peoples’ rights in international investment agreements. Professor Gunn’s chapter begins by discussing some of the rights of Indigenous peoples that are potentially threatened by investment agreements, with a focus on land rights and the right to participate in decision-making on the basis of free, prior and informed consent. She concludes with a discussion of what measures need to be taken in investment agreements to ensure that Indigenous peoples’ rights are properly protected during the negotiation and implementation of investment agreements. This includes reference to the obligations of states and business enterprises to ensure that investment agreements protect Indigenous peoples’ rights while at the same time promoting foreign direct investment.
Posttraumatic stress disorder (PTSD) is the most highly co-occurring psychiatric disorder among veterans with cannabis use disorder (CUD). Despite some evidence that cannabis use prospectively exacerbates the course of PTSD, which in turn increases the risk for CUD, the causal nature of the relationship between cannabis and psychiatric comorbidity is debated. The longitudinal relationship between PTSD diagnosis and traumatic intrusion symptoms with cannabis use and CUD was examined using cross-lagged panel model (CLPM) analysis.
Prospective data from a longitudinal observational study of 361 veterans deployed post-9/11/2001 included PTSD and CUD diagnoses, cannabis use, and PTSD-related traumatic intrusion symptoms from the Inventory of Depression and Anxiety Symptoms.
A random intercept CLPM analysis that leveraged three waves (baseline, 6 months and 12 months) of cannabis use and PTSD-related intrusion symptoms to account for between-person differences found that baseline cannabis use was significantly positively associated with 6-month intrusion symptoms; the converse association was significant but reduced in magnitude (baseline use to 6-month intrusions: β = 0.46, 95% CI 0.155–0.765; baseline intrusions to 6-month use: β = 0.22, 95% CI −0.003 to 0.444). Results from the two-wave CLPM reveal a significant effect from baseline PTSD to 12-month CUD (β = 0.15, 95% CI 0.028–0.272) but not from baseline CUD to 12-month PTSD (β = 0.12, 95% CI −0.022 to 0.262).
Strong prospective associations capturing within-person changes suggest that cannabis use is linked with greater severity of trauma-related intrusion symptoms over time. A strong person-level directional association between PTSD and CUD was evident. Findings have significant clinical implications for the long-term effects of cannabis use among individuals with PTSD.
In a double-blind multicentre study of outpatients with DSM-III-R major depressive disorder, 129 sertraline and 129 placebo patients were evaluated over a 6-week period. Sertraline exhibited a significantly greater (P < 0.001) antidepressant effect compared to placebo as measured by the HAM-D, MADRS, CGI-S and CGI-I. In the subset of patients with severe depression (baseline HAM-D ≥ 25), sertraline was also significantly more effective than placebo (P < 0.05). Side effects were more commonly reported in sertraline (59%) compared to placebo (38%) patients; the most common being nausea, headache and insomnia. A subset of 107 patients (66 sertraline; 41 placebo) who were defined as responders (CGI-I of 1 or 2) after 6 weeks treatment were entered into a 20-week continuation phase. In this responder subset, there was continuing improvement in both groups of patients, but with no significant differences in mean HAM-D or MADRS between the groups. However, a higher number of sertraline patients were associated with a persistent pattern of improvement relative to placebo (P < 0.05). The incidence of side effects was similar in sertraline (52%) and placebo (49%) treated patients in the continuation period.
The Barents Sea region of Arctic Norway preserves a thick succession of marine and deltaic Triassic strata that yield an abundant and diverse association of terrestrial and marine palynomorphs. Despite being the principal means for dating and correlation across this vast region, the Upper Triassic palynozonal resolution has remained relatively low. This is problematic due to the thickness of the Upper Triassic Series and since this corresponds to the longest of the three Triassic epochs. This paper presents a refined Middle–Upper Triassic palynozonation for the region, based on a detailed investigation of multiple localities ranging from the Svalbard Archipelago to the southern Barents Sea. The zonation comprises eleven spore-pollen zones: the Carnisporites spiniger, Triadispora obscura and Protodiploxypinus decus zones (Anisian), the Echinitosporites iliacoides Zone (Ladinian), the Semiretisporis hochulii, Podosporites vigraniae, Leschikisporis aduncus, and Protodiploxypinus spp. zones (Carnian), the Classopollis torosus, and Quadraeculina anellaeformis zones (Norian), and the Ricciisporites spp. Zone (Rhaetian). Additionally, two new dinoflagellate cyst zones are defined: the Rhaetogonyaulax arctica (upper Carnian – lower Norian) and Rhaetogonyaulax rhaetica (lower Norian) zones. Three new age-significant palynomorph taxa are described: Kyrtomisporis moerki sp. nov., Podosporites vigraniae sp. nov. and Semiretisporis hochulii sp. nov. The revised palynozonation is compared with previous palynozonal schemes for the Greater Barents Sea region, and its relationship to Triassic palaeoclimate, palaeoenvironments and sequence stratigraphy is discussed.
Primary care practitioners (PCPs) do not routinely promote dementia risk reduction. The purpose of this study was to map the published literature on the views of PCPs about dementia risk reduction, in order to identify implementation constructs and strategies crucial to the development of an implementation intervention to support dementia risk reduction in primary care. We undertook a scoping review of the PCPs’ views about promoting brain health for reducing dementia risk. We searched MEDLINE, PsycINFO, CINAHL, and Embase for English-language articles published between 1995 and December 2017. We then applied the Consolidated Framework for Implementation Research (CFIR) and matched Expert Recommendations for Implementing Change to the scoping review findings in order to develop a preliminary implementation model. Eight articles reported views of PCPs about dementia prevention. Study findings were mapped to 5 of the 39 CFIR constructs: (i) knowledge and beliefs about dementia risk reduction, (ii) evidence strength and quality, (iii) relative priority, (iv) available resources, and (v) external policy and incentives. The findings suggest implementation strategies to consider in our preliminary model include (i) educational meetings, (ii) identifying and preparing champions, (iii) conducting local consensus discussions, (iv) altering incentive structures, and (v) capturing and sharing local knowledge. There have been few studies about the views of PCPs about dementia risk reduction. Implementation in the primary care setting is fundamental to early identification of risk and supporting preventive practices, but it needs to focus on more than just education for PCPs. We need more up-to-date and in-depth data on the views of PCPs about dementia risk reduction and context-specific analyses of implementation needs. Further research into effective primary care interventions to reduce dementia risk is expected to support implementation efforts.
“I am a poor hand at this form of communication,” wrote Samuel Beckett in a letter to Lawrence Shainberg. This was by no means his sole apology for what he perceived to be his inadequacy as a correspondent. Yet by the time he claimed this, he had already written something in the order of fifteen thousand letters – over a long life, certainly, but with a frequency nonetheless of something like one letter (or lettercard or picture postcard) per day, every day of his adulthood (excepting the years of World War II).It took the four editors working on his correspondence, of which team I was the youngest member, some thirty years to assemble what Beckett wrote to friends, colleagues, publishers, theater directors, academics, actors, admirers; and then, from this corpus, to select the approximately 20 percent that would become the four volumes of the Cambridge University Press edition of The Letters of Samuel Beckett.
Crucial to health and social care practice, the Mental Capacity Act (MCA) 2005 safeguards decision-making within a legal framework. This book provides theoretical, practical and up-to-date guidance on mental capacity legislation. It focuses on the theory underpinning the principles of the MCA 2005, including historical background, and the practical challenges in applying legal statute in varied clinical settings, from hospitals to social care in community settings. Recent case law is detailed, and examples of ethical dilemmas and medico-legal challenges feature, along with guidance to navigate these in clinical practice. Applying mental capacity principles in end-of-life decision-making is an area of discussion, as well as the future of legislative changes in the field. To be read alongside the MCA 2005 Code of Practice, this guide will support mental health and social care professionals in clinical settings.
OBJECTIVES/SPECIFIC AIMS: 1.Identify barriers to pursuing research for physician trainees 2.Develop a sustainable pipeline of physician-scientists at Duke 3.Coordinate physician-scientist development programs across the School of Medicine under one central Office 4.Provide infrastructure and resources for all physician-scientists 5.Increase the number of MDs and MD/PhDs who pursue, succeed, and are retained in research METHODS/STUDY POPULATION: To establish a baseline understanding of the needs and concerns of physician-scientist trainees at Duke, we conducted focus groups using a standardized interview guide and thematic analysis. Findings from these focus groups were used to develop a framework for support, leading to the creation of the Office of Physician-Scientist Development (OPSD) housed centrally within the Duke School of Medicine. The OPSD integrates programs and resources for multiple populations including medical students, residents, fellows, junior faculty, and faculty mentors. Pipeline programs will also be developed to enhance research engagement in targeted student populations prior to medical school. RESULTS/ANTICIPATED RESULTS: A total of 45 students and faculty participated in the focus groups and structured interviews (1st year medical student, n=11; 4th year medical students, n=11; residents/fellows, n=13; junior faculty, n=11). While participants raised a number of specific issues, one key message emerged: non-PhD MDs in basic research felt they lacked opportunities for directed training. Moreover, they felt the need to teach themselves many critical skills through trial and error. This has led to perceptions that they cannot compete effectively with PhDs and MD-PhD scientists for research funding and positions. Consensus recommendations included: better guidance in choosing mentors, labs, and projects; central resource for information relevant to physician scientists; training specifically tailored to physician scientists conducting laboratory-based research; improved infrastructure and well-defined training pathways; and assistance with grant preparation. To-date, over 90 students, residents, and fellows have been identified who identify as laboratory-based physician scientists. Additional efforts are underway to identify and characterize the broader range of physician-scientist students and trainees at Duke. DISCUSSION/SIGNIFICANCE OF IMPACT: Our planning study revealed specific steps forward toward developing a robust community of physician-scientists at Duke. As a first step, the Dean of the School of Medicine has appointed an Associate Dean of Physician-Scientist Development to oversee a new Office of Physician-Scientist Development (OPSD) being launched in December of 2018. The OPSD will offer four primary programs. 1) A concierge mentoring program will assist new trainees in identifying research areas of interest and mentors. Trainees will receive periodic contact to provide additional support as needed and promote success. 2) A physician-scientist training program is being created to provide training specific to laboratory research skills as well as career and professional development training to complement existing clinical and translational research programs. 3) Integrated training pathways will provide additional mentored research training for those pursuing research careers. Pathways will capitalize on existing resources from R38 programs, while pursuing additional R38 and R25 support. 4) An MD-Scientist funding program has been developed to provide additional research funding and protected time for students pursuing a second research year. Through the support and programming offered by the OPSD, we anticipate decreased perceptions of barriers to pursuing a physician-scientist career and increased satisfaction with training opportunities. Over time, we expect such support to increase the number of MD students pursuing research as a career and the number of residents, fellows, and MD junior faculty remaining in research careers.