8 research outputs found
A Diverse Clinical-Based Practice in Teacher Education
The purpose of the study was to determine if offering a virtual clinical-based practice would affect teacher candidatesâ level of confidence in teaching diverse students. During 2012-2014, data were collected using a pre- and post-Likert scale questionnaire. A paired two sample t-test was utilized to determine if there was a significant difference in mean scores from the pre- to the postquestionnaire. Increases were found in all questionnaire items with five of the items showing a significant increase at the α=.01 level. The results suggest that a virtual clinical-based practice may provide an authentic experience for teacher candidates, may lead teacher candidates to be become more aware and take a positive approach to studentsâ differences, and that the teacher candidatesâ comfort level with unfamiliar situations posed by students from diverse backgrounds may increase. A future implication is that colleges of education may want to consider adding a virtual clinical-based practice to existing diversity education classes. However, more research needs to be conducted to determine if virtual clinical-based practices are equal to or better than on-site clinical-based practices in an attempt to increase teacher candidatesâ levels of confidence in teaching diverse students
Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe
The genetic architecture of the human cerebral cortex
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
Myeloid Cell-associated Resistance to PD-1/PD-L1 Blockade in Urothelial Cancer Revealed Through Bulk and Single-cell RNA Sequencing
Purpose To define dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR)â=â1.21), 95% confidence interval (95% CIâ=â1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HRâ=â0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers
Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment
Background: Increasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up. Methods: Four hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests. Results: While controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gait (HR = 1.7), MMSE (HR = 1.09), and DSST (HR = 1.03) covariates showed a higher impact on AD dementia conversion. Conclusions: The importance of the link between gait and related cognitive functions in terms of diagnosis, prognosis, and rehabilitation in aMCI is critical. We showed that in aMCI gait abnormalities lead to executive functions/attention deterioration and conversion to AD dementia
Pregnancy and neonatal outcomes of COVID -19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries
Objective
Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARSâCoVâ2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVIDâ19 (PANâCOVID) study and the American Academy of Pediatrics (AAP) Section on NeonatalâPerinatal Medicine (SONPM) National Perinatal COVIDâ19 Registry.
Methods
This was an analysis of data from the PANâCOVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARSâCoVâ2 infection at any stage in pregnancy, and the AAPâSONPM National Perinatal COVIDâ19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARSâCoVâ2 from 14âdays before delivery to 3âdays after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PANâCOVID results are presented overall for pregnancies with suspected or confirmed SARSâCoVâ2 infection and separately in those with confirmed infection.
Results
We report on 4005 pregnant women with suspected or confirmed SARSâCoVâ2 infection (1606 from PANâCOVID and 2399 from AAPâSONPM). For obstetric outcomes, in PANâCOVID overall and in those with confirmed infection in PANâCOVID and AAPâSONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (<â37âweeks' gestation) in 12.0% of all women in PANâCOVID, in 16.1% of those women with confirmed infection in PANâCOVID and in 15.7% of women in AAPâSONPM. Extreme preterm delivery (<â27âweeks' gestation) occurred in 0.5% of cases in PANâCOVID and 0.3% in AAPâSONPM. Neonatal SARSâCoVâ2 infection was reported in 0.9% of all deliveries in PANâCOVID overall, in 2.0% in those with confirmed infection in PANâCOVID and in 1.8% in AAPâSONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a smallâforâgestationalâage (SGA) neonate were 8.2% in PANâCOVID overall, 9.7% in those with confirmed infection and 9.6% in AAPâSONPM. Mean gestationalâageâadjusted birthâweight Zâscores were â0.03 in PANâCOVID and â0.18 in AAPâSONPM.
Conclusions
The findings from the UK and USA registries of pregnancies with SARSâCoVâ2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PANâCOVID study, although not in the AAPâSONPM study. The data presented support strong guidance for enhanced precautions to prevent SARSâCoVâ2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd