55 research outputs found
Applying Task Force Recommendations on Integrating Science and Practice in Health Service Psychology Education
The proper role of research skills and training to conduct research in professional psychology education has been controversial throughout the history of the field. An extensive effort was undertaken recently to address that issue and identify ways the field might move forward in a more unified manner. In 2015, the American Psychological Association (APA) Board of Educational Affairs convened a task force to address one of the recommendations made by the Health Service Psychology Education Collaborative in 2013. That recommendation stated that the education and training of health service psychologists (HSPs) include an integrative approach to science and practice that incorporates scientific-mindedness, training in research skills, and goes well beyond merely âconsumingâ research findings. The task force subsequently developed recommendations related to the centrality of science competencies for HSPs and how these competencies extend beyond training in evidence-based practice. This article discusses the findings of the task force and the implications of its recommendations for education and training in HSP. The challenges and opportunities associated with implementing these recommendations in HSP graduate programs are examined
Exploring Perceived Importance of a Novel Emergency Food Program during COVID-19 and Program Recipient Characteristics
Following rising unemployment rates and consequent loss of income due to COVID-19, many people have been seeking meal assistance. This study examines the impact of a community-based free meal distribution program during the pandemic in Kentucky, reviewing characteristics of recipients of the program. Demographics, health behaviors, food insecure classification, and rating of importance of the meal program were collected. Qualitative feedback on the impact of the program was collected via open response. Of the 92 participants using the meal service, the cohort was female, Black, 43 years of age (43.5 ± 15.0 years), with a household income under 30,000 USD before COVID, decreased income since COVID, and were food insecure. Recipients rated the importance of the service as 8.7 ± 1.8 (of 10), and those with children indicated the importance as 4.2 ± 1.1 (of 5). Qualitative data on program importance highlighted four response categories including âchanged habitsâ, âmental wellbeingâ, âprovided resourcesâ, and âotherâ. In response to the COVID-19 pandemic, many individuals have struggled. Meal assistance programs are a fundamental asset in the community that have seen marketed demand since COVID-19. Collaboration with, and evaluation of, meal assistance programs can be valuable for continued programmatic funding support
Bullying at Work and Its Impact on Job Satisfaction: An Exploration of School Psychologists
Given the persistent national shortage of school psychologists, as well as their job retention concerns, likely related to burnout, it is necessary to examine any factors that negatively impact school psychologistsâ job satisfaction. In this sample of 94 Pennsylvania school psychologists, the experience of being bullied at work was associated with diminished job satisfaction. Specifically, the independent variables of being bullying at work predicted 18.2% of the variance in job satisfaction in this sample, with verbal and indirect bullying the only types of bullying that contributed a significant amount of the variance. This study indicates that this issue should be closely monitored by management and addressed promptly
Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors
<p>Abstract</p> <p>Background</p> <p>Activating mutations in Kit receptor tyrosine kinase or the related platelet-derived growth factor receptor (PDGFR) play an important role in the pathogenesis of gastrointestinal stromal tumors (GIST).</p> <p>Methods</p> <p>This study investigated the activity of motesanib, an inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3; PDGFR; and Kit, against primary activating Kit mutants and mutants associated with secondary resistance to imatinib. Single- and double-mutant isoforms of Kit were evaluated for their sensitivity to motesanib or imatinib in autophosphorylation assays and in Ba/F3 cell proliferation assays.</p> <p>Results</p> <p>Motesanib inhibited Kit autophosphorylation in CHO cell lines expressing primary activating mutations in exon 9 (AYins503-504, IC<sub>50 </sub>= 18 nM) and exon 11 (V560 D, IC<sub>50 </sub>= 5 nM; Î552-559, IC<sub>50 </sub>= 1 nM). Motesanib also demonstrated activity against kinase domain mutations conferring imatinib resistance (V560D/V654A, IC<sub>50 </sub>= 77 nM; V560D/T670I, IC<sub>50 </sub>= 277 nM; Y823 D, IC<sub>50 </sub>= 64 nM) but failed to inhibit the imatinib-resistant D816V mutant (IC<sub>50 </sub>> 3000 nM). Motesanib suppressed the proliferation of Ba/F3 cells expressing Kit mutants with IC<sub>50 </sub>values in good agreement with those observed in the autophosphorylation assays.</p> <p>Conclusions</p> <p>In conclusion, our data suggest that motesanib possesses inhibitory activity against primary Kit mutations and some imatinib-resistant secondary mutations.</p
Development and Initial Validation of a Self-Scored COPD Population Screener Questionnaire (COPD-PS)
COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated. We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD. COPD-PSâą development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5). A national survey of 697 patients was conducted at 12 practitioner sites. Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%). ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity. Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations. For known-groups validation, COPD-PS differences between clinical groups were tested. Test-retest reliability was evaluated in a 20% sample. Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO. Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age. COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91). Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3). Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems. With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%. The COPD-PS accurately classified physician-reported COPD (AUC = 0.89). The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD
Efficient Generation of Germ Line Transmitting Chimeras from C57BL/6N ES Cells by Aggregation with Outbred Host Embryos
Genetically modified mouse strains derived from embryonic stem (ES) cells have become essential tools for functional genomics and biomedical research. Large scale mutagenesis projects are producing libraries of mutant C57BL/6 (B6) ES cells to enable the functional annotation of every gene of the mouse genome. To realize the utility of these resources, efficient and accessible methods of generating mutant mice from these ES cells are necessary. Here, we describe a combination of ICR morula aggregation and a chemically-defined culture medium with widely available and accessible components for the high efficiency generation of germline transmitting chimeras from C57BL/6N ES cells. Together these methods will ease the access of the broader biomedical research community to the publicly available B6 ES cell resources
Insights into the Musa genome: Syntenic relationships to rice and between Musa species
<p>Abstract</p> <p>Background</p> <p><it>Musa </it>species (Zingiberaceae, Zingiberales) including bananas and plantains are collectively the fourth most important crop in developing countries. Knowledge concerning <it>Musa </it>genome structure and the origin of distinct cultivars has greatly increased over the last few years. Until now, however, no large-scale analyses of <it>Musa </it>genomic sequence have been conducted. This study compares genomic sequence in two <it>Musa </it>species with orthologous regions in the rice genome.</p> <p>Results</p> <p>We produced 1.4 Mb of <it>Musa </it>sequence from 13 BAC clones, annotated and analyzed them along with 4 previously sequenced BACs. The 443 predicted genes revealed that Zingiberales genes share GC content and distribution characteristics with eudicot and Poaceae genomes. Comparison with rice revealed microsynteny regions that have persisted since the divergence of the Commelinid orders Poales and Zingiberales at least 117 Mya. The previously hypothesized large-scale duplication event in the common ancestor of major cereal lineages within the Poaceae was verified. The divergence time distributions for <it>Musa</it>-Zingiber (Zingiberaceae, Zingiberales) orthologs and paralogs provide strong evidence for a large-scale duplication event in the <it>Musa </it>lineage after its divergence from the Zingiberaceae approximately 61 Mya. Comparisons of genomic regions from <it>M. acuminata </it>and <it>M. balbisiana </it>revealed highly conserved genome structure, and indicated that these genomes diverged circa 4.6 Mya.</p> <p>Conclusion</p> <p>These results point to the utility of comparative analyses between distantly-related monocot species such as rice and <it>Musa </it>for improving our understanding of monocot genome evolution. Sequencing the genome of <it>M. acuminata </it>would provide a strong foundation for comparative genomics in the monocots. In addition a genome sequence would aid genomic and genetic analyses of cultivated <it>Musa </it>polyploid genotypes in research aimed at localizing and cloning genes controlling important agronomic traits for breeding purposes.</p
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, PÂ =Â 1.65Â ĂÂ 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, PÂ =Â 2.3Â ĂÂ 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, PÂ =Â 3.98Â ĂÂ Â 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, PÂ =Â 4.99Â ĂÂ 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)
Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study
BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47â795 (75·2%) of 63â525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11â185 [86·6%] of 12â909 vs 36â415 [72·4%] of 50â278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70â0·89], p=0·0001, for 70â79 years; 0·52 [0·46â0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75â80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council
- âŠ