Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Finding their way home: The reunification of First Nations adoptees

Entire generations of First Nations people have been separated from their birth families and tribes by historical acts of relocation, boarding schools, and the adoption era. Reunification is an essential component to rebuilding the First Nations population. It is echoed across tribes captured by the phrase, “generation after generation we are coming home” (White Hawk, 2014). The purpose of this study was to investigate personal and social identity indicators that contribute to a satisfactory reunification for 95 First Nations adult adoptees who were separated from their birth families during childhood by foster-care and/or adoption. Retrospective survey data originated from the Experiences of Adopted and Fostered Individuals Project. The overall model of satisfactory reunification was statistically significant, and explained 16.6% of the total variance. The study’s findings revealed two social identity variables were statistically significant in relation to the reunification experience – high social connection to tribe (positive relationship) and reunification with the birthmother (negative relationship). First Nations adoptees have not only a biological/birth family to return to, but also a tribe, and ancestral land. Components of social identity are particularly important for the reunification process of First Nations adoptees. Reconnection with extended family and social connection to tribe play a critical role in bettering the reunification experience from the adoptee’s perspective.

Internalizing and externalizing behavioral problems of American Indian children in the child welfare system.

Children involved in the child welfare system display elevated or clinically significant behavioral problems. However, there is a dearth of literature on the behavioral problems of American Indian children following child welfare involvement. Grounded in Patterson\u27s Family Adjustment and Adaptation Response theory, this study fills that gap. Baseline, 18-month, and 36-month follow-up data from the National Survey of Child and Adolescent Well-being were utilized. The sample (n = 3498) consisted of American Indian, African American, and Caucasian children ages 2–16 at baseline (M = 8.13 years old, SD = 3.85) and 51.7% were female. Nearest neighbor propensity score matching analyses were used to estimate the effect of race on clinically significant internalizing and externalizing behavioral problems. Findings suggest that although externalizing behavioral problems do not differ based on race after controlling for other important factors, internalizing behavioral problems do differ. American Indian children are more likely to display clinically significant internalizing behavioral problems

She3p Possesses a Novel Activity Required for ASH1 mRNA Localization in Saccharomyces cerevisiae▿

Intracellular and intercellular polarity requires that specific proteins be sorted to discreet locations within and between cells. One mechanism for sorting proteins is through RNA localization. In Saccharomyces cerevisiae, ASH1 mRNA localizes to the distal tip of the bud, resulting in the asymmetric sorting of the transcriptional repressor Ash1p. ASH1 mRNA localization requires four cis-acting localization elements and the trans-acting factors Myo4p, She3p, and She2p. Myo4p is a type V myosin motor that functions to directly transport ASH1 mRNA to the bud. She2p is an RNA-binding protein that directly interacts with the ASH1 mRNA cis-acting elements. Currently, the role for She3p in ASH1 mRNA localization is as an adaptor protein, since it can simultaneously associate with Myo4p and She2p. Here, we present data for two novel mutants of She3p, S348E and the double mutant S343E S361E, that are defective for ASH1 mRNA localization, and yet both of these mutants retain the ability to associate with Myo4p and She2p. These observations suggest that She3p possesses a novel activity required for ASH1 mRNA localization, and our data imply that this function is related to the ability of She3p to associate with ASH1 mRNA. Interestingly, we determined that She3p is phosphorylated, and global mass spectrometry approaches have determined that Ser 343, 348, and 361 are sites of phosphorylation, suggesting that the novel function for She3p could be negatively regulated by phosphorylation. The present study reveals that the current accepted model for ASH1 mRNA localization does not fully account for the function of She3p in ASH1 mRNA localization

The Reunification of American Indian Children in Long-term Foster Care

Objective: The literature examining reunification for American Indian children reveals mixed findings regarding racial differences. Studies that isolate the impact of race on reunification while controlling for other covariates are needed, and this study fills that gap. Method: Data are from the long-term foster care sample of the National Survey of Child and Adolescent Well-Being (NSCAW I). We examined a sample (N = 456) of American Indian, African American, and White children ages 2–15 at baseline (M = 7.98 years, SD = 4.17). Using nearest-neighbor propensity score matching, we estimated the effect of race on reunification at 18- and 36-month follow-up. We used logistic regression analyses to explore factors associated with reunification in addition to race. Results: Our findings suggest that reunification rates do not differ based on race after controlling for other factors. American Indian children were statistically no more or less likely to reunify than their White or African American peers. Conclusions: Lower rates of reunification for American Indian children may be better explained by covariates in the propensity score model and regression analyses (e.g., age, emotional–behavioral problems, type of placement) rather than race

Nonsense-Mediated Decay of ash1 Nonsense Transcripts in Saccharomyces cerevisiae

Nonsense-mediated mRNA decay (NMD) performs two functions in eukaryotes, one in controlling the expression level of a substantial subset of genes and the other in RNA surveillance. In the vast majority of genes, nonsense mutations render the corresponding transcripts prone to surveillance and subject to rapid degradation by NMD. To examine whether some classes of nonsense transcripts escape surveillance, we asked whether NMD acts on mRNAs that undergo subcellular localization prior to translation. In Saccharomyces cerevisiae, wild-type ASH1 mRNA is one of several dozen transcripts that are exported from the mother-cell nucleus during mitotic anaphase, transported to the bud tip on actin cables, anchored at the bud tip, and translated. Although repressed during transport, translation is a prerequisite for NMD. We found that ash1 nonsense mutations affect transport and/or anchoring independently of NMD. The nonsense transcripts respond to NMD in a manner dependent on the position of the mutation. Maximal sensitivity to NMD occurs when transport and translational repression are simultaneously impaired. Overall, our results suggest a model in which ash1 mRNAs are insensitive to NMD while translation is repressed during transport but become sensitive once repression is relieved

The role of firm resource demand in shoppers' service experiences

Firms are using more customer resources to increase the economic value of the service exchange. However, positive outcomes for a firm are not solely based on demanding more resource inputs from customers. In order to achieve a satisfactory service encounter for the firm and the customer, a firm must understand how a customer views the resource demands placed on them. This dissertation examines the conditions under which differing levels of firm resource demand improve or diminish the customer value through the customer's perceived effort, the equitability of the service exchange, and the overall satisfaction with the service experience. A number of boundary conditions built around customers' intrinsic and extrinsic motivations are expected to influence these relationships, including the customers' shopping enjoyment, the customers' value shopping orientation, and the firm provided rewards. In order to better understand how customers react to the demands firms place upon them, two studies are conducted. The first study uses a critical incident technique survey to explore the different demands placed on customers during a service encounter and the customers' reactions to those demands. The results from study one indicates that firms demand the use of a number of customer resources to complete a service encounter. Three main resource categories (financial, time, and knowledge) and a number of subcategories emerged from the data. The second study, a scenario-based experiment, examines the hypotheses developed from previous literature and the first study. The findings from study two provide managers' actionable insights into the costs and benefits of increasing the input demand placed on customers. Theoretically, the findings provide scholars with information about the psychological and behavioral reactions of customers to differing input demand levels. (Published By University of Alabama Libraries