Stress and trauma research has traditionally focused on negative sequelae of adversity. Recently, research has begun to focus on positive outcomes, specifically posttraumatic growth (PTG) – “positive ...change experienced as a result of the struggle with trauma” – which emphasizes the transformative potential of one's experiences with highly stressful events and circumstances. The positive changes of PTG are generally thought to occur in five domains: new possibilities, relating to others, personal strength, appreciation of life, and spiritual change. The study of PTG has, for the most part, been centered on adults, and not until very recently has there been sufficient research on PTG among children and adolescents to justify a review. The current systematic review of the literature on PTG among children and adolescents included 25 studies that tested associations between PTG and conceptually-relevant variables found to be associated with PTG in adults and hypothesized to play similar roles in young people, including environmental characteristics, distress responses, social processes, psychological processes, positive outcomes, and demographic variables. Links were made between a theoretical model of PTG among youth and findings of the current review. Limitations and recommendations for future research are discussed.
► Ties between PTG and stress/distress, social/religious support, coping, and health. ► Youth PTG may decay over time more quickly than does PTG in adults. ► PTG may be optimal during late adolescence and moderate trauma severity and PTSS. ► Gender differences (females report more PTG) may not emerge until early adulthood. ► Potential utility of PTG to catalyze long-term positive change beyond itself.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Human breast cancers that exhibit high proportions of immune cells and elevated levels of pro-inflammatory cytokines predict poor prognosis. Here, we demonstrate that treatment of human MCF-7 breast ...cancer cells with pro-inflammatory cytokines results in ERα-dependent activation of gene expression and proliferation, in the absence of ligand or presence of 4OH-tamoxifen (TOT). Cytokine activation of ERα and endocrine resistance is dependent on phosphorylation of ERα at S305 in the hinge domain. Phosphorylation of S305 by IKKβ establishes an ERα cistrome that substantially overlaps with the estradiol (E2)-dependent ERα cistrome. Structural analyses suggest that S305-P forms a charge-linked bridge with the C-terminal F domain of ERα that enables inter-domain communication and constitutive activity from the N-terminal coactivator-binding site, revealing the structural basis of endocrine resistance. ERα therefore functions as a transcriptional effector of cytokine-induced IKKβ signaling, suggesting a mechanism through which the tumor microenvironment controls tumor progression and endocrine resistance.
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•ERα is a signaling effector of pro-inflammatory cytokines in breast cancer cells•IL1β and TNFα increase breast cancer invasiveness dependent on ERα•Cytokines activate unliganded ERα via IKKβ phosphorylation of S305•Phospho-S305 results in structural changes of ERα and tamoxifen resistance
Stender et al. show that inflammatory cytokines activate unliganded ERα though kinase-dependent phosphorylation. This phosphorylation causes structural changes on ERα that lead to transcriptional activation, endocrine resistance, and enhanced invasiveness of breast cancer cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Quantitative genetics theory predicts that X-chromosome dosage compensation (DC) will have a detectable effect on the amount of genetic and therefore phenotypic trait variances at associated loci in ...males and females. Here, we systematically examine the role of DC in humans in 20 complex traits in a sample of more than 450,000 individuals from the UK Biobank and 1600 gene expression traits from a sample of 2000 individuals as well as across-tissue gene expression from the GTEx resource. We find approximately twice as much X-linked genetic variation across the UK Biobank traits in males (mean h
= 0.63%) compared to females (mean h
= 0.30%), confirming the predicted DC effect. Our DC estimates for complex traits and gene expression are consistent with a small proportion of genes escaping X-inactivation in a trait- and tissue-dependent manner. Finally, we highlight examples of biologically relevant X-linked heterogeneity between the sexes that bias DC estimates if unaccounted for.
Objective: This study used a mixed method, prospective, multi-informant design to (a) identify coping strategies used by youth residing in urban poverty and (b) test whether these coping strategies ...buffer the effects of stress exposure when adult support is present and when absent. Method: There were 286 youth ages 10 to 16 (mean age at Time 1 = 13; 65% female; 34% male; 1% not identified; 46% African American; 25% Latino; 11% European American; 8% Asian American, 4% Mixed/Biracial, 6% Other) and their parents who participated. Thematic analyses were used to code adolescent interviews about protective factors to identify specific coping strategies used. Hierarchical regression analyses tested whether these coping strategies moderate the association between stress exposure and psychological symptoms for youth with and without adult support. Results: Youth identified multiple coping strategies as protective including Expressing Oneself, Self-Soothing, Seeking Help, Seeking Safety, Distraction, Problem-Solving, Self-Care, and Avoidance. A number of these coping strategies (Expressing Oneself, Self-Soothing, Seeking Help, and Seeking Safety) attenuated the association between stressors and psychological symptoms over time for youth with adult support. For youth without adult support, a number of the strategies they identified as protective (Distraction, Problem-Solving, and Self-Care) accentuated the association between stress exposure and psychological symptoms over time. The only strategy that proved protective for youth without adult support was avoidance. Conclusions: Findings suggest that youth require adult support to effectively make use of a range of coping strategies and that avoidance is the sole effective strategy for youth without support.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
As governments, funding agencies and research organisations worldwide seek to maximise both the financial and non-financial returns on investment in research, the way the research process is ...organised and funded is becoming increasingly under scrutiny. There are growing demands and aspirations to measure research impact (beyond academic publications), to understand how science works, and to optimise its societal and economic impact. In response, a multidisciplinary practice called research impact assessment is rapidly developing. Given that the practice is still in its formative stage, systematised recommendations or accepted standards for practitioners (such as funders and those responsible for managing research projects) across countries or disciplines to guide research impact assessment are not yet available.In this statement, we propose initial guidelines for a rigorous and effective process of research impact assessment applicable to all research disciplines and oriented towards practice. This statement systematises expert knowledge and practitioner experience from designing and delivering the International School on Research Impact Assessment (ISRIA). It brings together insights from over 450 experts and practitioners from 34 countries, who participated in the school during its 5-year run (from 2013 to 2017) and shares a set of core values from the school's learning programme. These insights are distilled into ten-point guidelines, which relate to (1) context, (2) purpose, (3) stakeholders' needs, (4) stakeholder engagement, (5) conceptual frameworks, (6) methods and data sources, (7) indicators and metrics, (8) ethics and conflicts of interest, (9) communication, and (10) community of practice.The guidelines can help practitioners improve and standardise the process of research impact assessment, but they are by no means exhaustive and require evaluation and continuous improvement. The prima facie effectiveness of the guidelines is based on the systematised expert and practitioner knowledge of the school's faculty and participants derived from their practical experience and research evidence. The current knowledge base has gaps in terms of the geographical and scientific discipline as well as stakeholder coverage and representation. The guidelines can be further strengthened through evaluation and continuous improvement by the global research impact assessment community.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study aimed to test a longitudinal model of trust in adults and psychological well‐being among Latinx adolescents, a population that has received little attention in the trust literature. The ...participants were urban, low‐income Latinx (N = 294) students at two urban, Midwestern high schools who indicated they had at least one natural mentor in 9th grade. Participants completed surveys at two‐time points, in 9th and 10th grade, and responded to measures of their feelings toward adults, quality of their natural mentoring relationships, self‐esteem, intrinsic academic motivation, and coping self‐efficacy. More trust in adults was indirectly, but not directly, associated with higher coping self‐efficacy via higher mentoring relational quality and self‐esteem. Positive expectations of adults may open Latinx youth to closeness in natural mentoring relationships and positive self‐perceptions, which may, in turn, bolster coping ability.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
In the first half of this review, the authors critically evaluate existing research on the association between stressors and symptoms of psychopathology in children and adolescents. This analysis ...reveals (a) problems with conceptualizations of stress, (b) variability in measurement of stressors, and (c) lack of theory-driven research. To address these problems, the authors propose a general conceptual model of the relation between stressors and child and adolescent psychopathology. The authors examine basic tenets of this general model in the second half of this article by testing a specific model in which negative parenting mediates the relation between economic stressors and psychological symptoms in young people. Results generally provide support for the specific model as well as for the broader model.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
We reviewed invasive Nocardia infections in 3 noncontiguous geographic areas in the United States during 2011–2018. Among 268 patients with invasive nocardiosis, 48.2% were from Minnesota, 32.4% from ...Arizona, and 19.4% from Florida. Predominant species were N. nova complex in Minnesota (33.4%), N. cyriacigeorgica in Arizona (41.4%), and N. brasiliensis in Florida (17.3%). Transplant recipients accounted for 82/268 (30.6%) patients overall: 14 (10.9%) in Minnesota, 35 (40.2%) in Arizona, and 33 (63.5%) in Florida. Manifestations included isolated pulmonary nocardiosis among 73.2% of transplant and 84.4% of non–transplant patients and central nervous system involvement among 12.2% of transplant and 3.2% of non–transplant patients. N. farcinica (20.7%) and N. cyriacigeorgica (19.5%) were the most common isolates among transplant recipients and N. cyriacigeorgica (38.0%), N. nova complex (23.7%), and N. farcinica (16.1%) among non–transplant patients. Overall antimicrobial susceptibilities were similar across the 3 study sites.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antibodies to programmed death-1 receptor and its ligand (anti–PD-1/PD-L1) produce durable responses in many cancers. However, the long-term effects of anti–PD-1/PD-L1 blockade are not well defined. ...We identified the toxicities, health outcomes and health-related quality of life (HRQoL) amongst long-term survivors treated with anti–PD-1/PD-L1.
We assessed 217 patients who received anti–PD-1/PD-L1 for melanoma, renal cell carcinoma or non–small-cell lung carcinoma between 2009 and 2017, with survival greater than two years after treatment. Patient and tumour characteristics, immune-related adverse events (irAEs), cardiometabolic parameters (glucose, blood pressure, body mass index BMI), body composition (using automated body composition analyser, computed tomography and Slice-o-matic software) and HRQoL outcomes were tracked.
Among the included patients, most were men (70.3%) and at anti–PD-1/PD-L1 initiation had an average age of 61.0 years and median BMI of 28.5. Median overall survival was not reached; 33 (15.2%) died during the follow-up primarily from progressive cancer (n = 28). At the last follow-up, most patients' Eastern Cooperative Oncology Group performance status was 0 (38%) or 1 (41%). There was no difference in blood pressure, glucose or BMI from baseline to two years after treatment initiation. Body composition showed increased adiposity (p = 0.05), skeletal muscle mass (p = 0.03) and skeletal muscle gauge (p = 0.04). We observed chronic irAEs at the last follow-up including hypothyroidism (10.6%), arthritis (3.2%), adrenal insufficiency (3.2%) and neuropathy (2.8%). New diagnoses of type 2 diabetes (6.5%) and hypertension (6.0%) were observed, with uncertain relationship to anti–PD-1/PD-L1. Patient-reported outcomes compared favourably with cancer and general populations, although younger age (p = 0.003) and need for subsequent therapy (p = 0.03) were associated with worse HRQoL outcomes.
Durable responses to anti–PD-1/PD-L1 therapy and favourable HRQoL outcomes are encouraging. Chronic events may be more common than previously thought although no clear chronic adverse cardiometabolic effects were observed.
•Of patients surviving >24 months after antibodies to programmed death-1 receptor and its receptor therapy, most had durable benefit.•Health-related quality of life outcomes compared favourably to unselected cancer cohorts.•Chronic immune-related adverse events may be more common than previously thought.•No obvious long-term adverse cardiometabolic signals were noted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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