Childhood Adversity Moderates Change in Latent Patterns of Psychological Adjustment during the COVID-19 Pandemic: Results of a Survey of U.S. Adults

Emerging evidence suggests that the consequences of childhood adversity impact later psychopathology by increasing individuals’ risk of experiencing difficulties in adjusting to stressful situations later in life. The goals of this study were to: (a) identify sociodemographic factors associated with subgroups of psychological adjustment prior to and after the onset of the COVID-19 pandemic and (b) examine whether and to what extent types of childhood adversity predict transition probabilities. Participants were recruited via multiple social media platforms and listservs. Data were collected via an internet-based survey. Our analyses reflect 1942 adults (M = 39.68 years); 39.8% reported experiencing at least one form of childhood adversity. Latent profile analyses (LPAs) and latent transition analyses (LTAs) were conducted to determine patterns of psychological adjustment and the effects of childhood adversity on transition probabilities over time. We identified five subgroups of psychological adjustment characterized by symptom severity level. Participants who were younger in age and those who endorsed marginalized identities exhibited poorer psychological adjustment during the pandemic. Childhood exposure to family and community violence and having basic needs met as a child (e.g., food, shelter) significantly moderated the relation between latent profile membership over time. Clinical and research implications are discussed

Clinically actionable mutation profiles in patients with cancer identified by whole-genome sequencing

Next-generation sequencing (NGS) efforts have established catalogs of mutations relevant to cancer development. However, the clinical utility of this information remains largely unexplored. Here, we present the results of the first eight patients recruited into a clinical whole-genome sequencing (WGS) program in the United Kingdom. We performed PCR-free WGS of fresh frozen tumors and germline DNA at 75× and 30×, respectively, using the HiSeq2500 HTv4. Subtracted tumor VCFs and paired germlines were subjected to comprehensive analysis of coding and noncoding regions, integration of germline with somatically acquired variants, and global mutation signatures and pathway analyses. Results were classified into tiers and presented to a multidisciplinary tumor board. WGS results helped to clarify an uncertain histopathological diagnosis in one case, led to informed or supported prognosis in two cases, leading to de-escalation of therapy in one, and indicated potential treatments in all eight. Overall 26 different tier 1 potentially clinically actionable findings were identified using WGS compared with six SNVs/indels using routine targeted NGS. These initial results demonstrate the potential of WGS to inform future diagnosis, prognosis, and treatment choice in cancer and justify the systematic evaluation of the clinical utility of WGS in larger cohorts of patients with cancer

A research agenda for seed-trait functional ecology

Trait-based approaches have improved our understanding of plant evolution, community assembly and ecosystem functioning. A major challenge for the upcoming decades is to understand the functions and evolution of early life-history traits, across levels of organization and ecological strategies. Although a variety of seed traits are critical for dispersal, persistence, germination timing and seedling establishment, only seed mass has been considered systematically. Here we suggest broadening the range of morphological, physiological and biochemical seed traits to add new understanding on plant niches, population dynamics and community assembly. The diversity of seed traits and functions provides an important challenge that will require international collaboration in three areas of research. First, we present a conceptual framework for a seed ecological spectrum that builds upon current understanding of plant niches. We then lay the foundation for a seed-trait functional network, the establishment of which will underpin and facilitate trait-based inferences. Finally, we anticipate novel insights and challenges associated with incorporating diverse seed traits into predictive evolutionary ecology, community ecology and applied ecology. If the community invests in standardized seed-trait collection and the implementation of rigorous databases, major strides can be made at this exciting frontier of functional ecology.Commonwealth Scientific and Industrial Research Organisation. Grant Number: R‐90470‐0

Exploring Appropriation of Global Cultural Rituals

Adolescents, as a consequence of identification with popular culture, have been described as having homogenous consumption patterns. More recently, however, it has been recognised that ‘glocalisation’ (global practices reworked to fit local contexts) affords an opportunity for differentiation. This paper considers a recent UK phenomenon, namely that of the US high school prom, and seeks to explore the ways in which this ritual has been adopted or adapted as part of youth culture. The method employed here was mixed methods and included in-depth interviews with those who attended a prom in the last three years as well as a questionnaire distributed amongst high school pupils who were anticipating a high school prom. The findings illustrate that the high school prom in the UK is becoming increasingly integrated into the fabric of youth culture although, depending on the agentic abilities employed by the emerging adults in the sample, there is differing appropriation of this ritual event particularly in relation to attitudes towards and motivations for attending the prom. A typology of prom attendees is posited. This paper contributes to our understanding of this practice in a local context

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Disparities between plant community responses to nitrogen deposition and critical loads in UK semi-natural habitats

Empirical critical loads are widely used to quantify and manage the ecological impacts of reactive nitrogen (N) deposition. Critical load values aim to identify a level of N deposition below which significant harmful effects do not occur according to present knowledge. Critical loads have been primarily based on experiments, but these are few in number and have well-known limitations, so there is a strong imperative to test and validate values with other forms of evidence. We assembled data on the spatial variability in vegetation communities in the United Kingdom and used Threshold Indicator Taxa Analyses (TITAN) to investigate linkages between species changes and modelled current and cumulative N deposition. Our analyses focused on five datasets: acid grasslands, alpine habitats, coastal fixed dunes, dune slacks and wet grasslands. In four of these habitats there was evidence for a significant decline in the cover of at least one species (a ‘species-loss change-point’) occurring below the critical load, and often at very low levels of N deposition. In all of the habitats there was evidence for clustering of many individual species-loss change-points, implying a community change-point analogous to an ecological threshold. Three of these community change-points occurred below the critical load and the remaining two overlapped with the critical load range. Studies using similar approaches are now increasingly common, with similar results. Across 19 similar analyses there has been evidence for plant species loss change-points below the critical load in 18 analyses, and community-level species loss change-points below the critical load in 13 analyses. None of these analyses has shown community change-points above the critical load. Field data increasingly suggest that many European critical loads are too high to confidently prevent loss of sensitive species

Germline MBD4-deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management