This study identified predictors of employment for individuals with traumatic brain injury (TBI). Data from 4,923 individuals with TBI were extracted from the Rehabilitation Services Administration’s ...Case Service Report (RSA-911) database. A multiple logistic regression model using demographics, disability-related variables, vocational rehabilitation (VR) service variables, and their interactions correctly classified 69.5% of the cases as successfully employed or not successfully employed. The model explained approximately 27.1% of the variance in employment outcomes. Results indicated that level of education, race/ethnicity, age at application, preemployment status, Supplemental Security Income (SSI), Social Security Disability Insurance (SSDI), comorbid depression, and case expenditure were significantly associated with employment outcomes (all p ≤ .05). VR variables that showed the most significant positive effect on employment outcomes were on-the-job support, job placement, and on-the-job training. Race/ethnicity moderated the effect of college training, supported employment, transportation, and extended evaluation or work trial assessment services on employment outcomes. The findings have implications for promoting the use of those VR services that are strongly related to employment outcomes for persons with TBI. They also point to the need for rehabilitation personnel to address some of the demographic and disability-related barriers to successful employment.
Measures were a substance dependence screening instrument and a questionnaire that inquired about participants' sociodemographic (for instance, age, gender, marital status, living arrangements, ...education, employment), psychological (for instance, history of sexual or physical victimization, social support), and disability-related (for instance, etiology, extent, and onset of visual impairment; public assistance or social insurance receipt; assistive technology and transportation use) characteristics, and substance use (for instance, alcohol, marijuana). Some of the chi-square analyses are suspect because one cell had an expected count of less than five cases. Since there are only 69 cases in the study, the number of variables in the logistic regression analysis had to be limited.
Congenital heart defects (CHD) are the leading cause of infant mortality among birth defects, and later morbidities and premature mortality remain problematic. Although genetic factors contribute ...significantly to cause CHD, specific genetic lesions are unknown for most patients. The National Heart, Lung, and Blood Institute-funded Pediatric Cardiac Genomics Consortium established the Congenital Heart Disease Genetic Network Study to investigate relationships between genetic factors, clinical features, and outcomes in CHD. The Pediatric Cardiac Genomics Consortium comprises 6 main and 4 satellite sites at which subjects are recruited, and medical data and biospecimens (blood, saliva, cardiovascular tissue) are collected. Core infrastructure includes an administrative/data-coordinating center, biorepository, data hub, and core laboratories (genotyping, whole-exome sequencing, candidate gene evaluation, and variant confirmation). Eligibility includes all forms of CHD. Annual follow-up is obtained for probands <1-year-old. Parents are enrolled whenever available. Enrollment from December 2010 to June 2012 comprised 3772 probands. One or both parents were enrolled for 72% of probands. Proband median age is 5.5 years. The one third enrolled at age <1 year are contacted annually for follow-up information. The distribution of CHD favors more complex lesions. Approximately, 11% of probands have a genetic diagnosis. Adequate DNA is available from 97% and 91% of blood and saliva samples, respectively. Genomic analyses of probands with heterotaxy, atrial septal defects, conotruncal, and left ventricular outflow tract obstructive lesions are underway. The scientific community's use of Pediatric Cardiac Genomics Consortium resources is welcome.
To identify a novel susceptibility gene for colorectal cancer (CRC), we conducted a genome-wide linkage analysis of 69 pedigrees segregating colorectal neoplasia in which involvement of known loci ...had been excluded, using a high-density single nucleotide polymorphism (SNP) array containing 10 204 markers. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of SNPs in strong linkage disequilibrium, we obtained a maximum non-parametric linkage statistic of 3.40 (P=0.0003) at chromosomal region 3q21–q24. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a dominant model (HLOD=3.10, genome-wide P=0.038) with 62% of families linked to the locus. We provide evidence for a novel CRC susceptibility gene. Further studies are needed to confirm this localization and to evaluate the contribution of this locus to disease incidence.
Mothers with a short cervix have been shown to have increased risk of spontaneous preterm delivery (PTD) and newborn morbidity. Those who require an ultrasound-indicated cerclage experience the ...highest rates of morbidity. Inflammation has been linked to a short cervix, and it has been linked to pregnancies affected by small for gestational age (SGA) newborns. To date, there are no studies that have investigated an association between a short cervix, with or without an ultrasound-indicated cerclage, and a SGA newborn.
This was a case-control study examining all pregnancies with a transvaginal cervical length <25 mm found at their second trimester anatomy scan. Cases were subdivided into those who received an ultrasound-indicated cerclage (Group 1, n = 52) and those who did not (Group 2, n = 139). Controls were defined as pregnancies with a transvaginal cervical length >25 mm with no cerclage (Group 3, n = 186) whose due date was within 2 months of the case pregnancy. Each short cervix case was matched with a control from group 3 in a 1:1 ratio. The primary outcome was birthweight <10% (SGA). Unadjusted data was analyzed with simple odds ratios. A logistic regression was used to control for confounding variables and provide an adjusted odds ratios (aOR).
The incidence of SGA among cases overall (group 1 + group 2) was 13.6% (26/191). In group 3, the SGA incidence was 4.3% (8/186). The adjusted odds ratio (aOR) for a SGA infant was significant, 2.8 (95% CI 1.2, 6.6). Subgroup analysis showed that Group 1 had an increased risk for an SGA infant aOR 4.9 (95% CI 1.8, 13.7), but Group 2 did not show a significant finding aOR 2.3 (95% CI 0.9, 5.7).
Pregnancies complicated by a short cervical length <25mm, with or without a cerclage, were associated with an increased risk for a SGA newborn. Most of this significance was due to the pregnancies which received an ultrasound-indicated cerclage for a mid-trimester short cervix.
Summary Background Amyloid-related imaging abnormalities (ARIA) have been reported in patients with Alzheimer's disease treated with bapineuzumab, a humanised monoclonal antibody against amyloid β. ...ARIA include MRI signal abnormalities suggestive of vasogenic oedema and sulcal effusions (ARIA-E) and microhaemorrhages and haemosiderin deposits (ARIA-H). Our aim was to investigate the incidence of ARIA during treatment with bapineuzumab, and evaluate associated risk factors. Methods Two neuroradiologists independently reviewed 2572 fluid-attenuated inversion recovery (FLAIR) MRI scans from 262 participants in two phase 2 studies of bapineuzumab and an open-label extension study. Readers were masked to the patient's treatment, APOE ε4 genotype, medical history, and demographics. Patients were included in risk analyses if they had no evidence of ARIA-E in their pre-treatment MRI, had received bapineuzumab, and had at least one MRI scan after treatment. We used Kaplan-Meier survival analysis to examine the distribution of incident ARIA-E from the start of bapineuzumab treatment and proportional hazards regression models to assess risk factors associated with ARIA. Findings 210 patients were included in the risk analyses. 36 patients (17%) developed ARIA-E during treatment with bapineuzumab; 15 of these ARIA-E cases (42%) had not been detected previously. 28 of these patients (78%) did not report associated symptoms. Adverse events, reported in eight symptomatic patients, included headache, confusion, and neuropsychiatric and gastrointestinal symptoms. Incident ARIA-H occurred in 17 of the patients with ARIA-E (47%), compared with seven of 177 (4%) patients without ARIA-E. 13 of the 15 patients in whom ARIA were detected in our study received additional treatment infusions while ARIA-E were present, without any associated symptoms. Occurrence of ARIA-E increased with bapineuzumab dose (hazard ratio HR 2·24 per 1 mg/kg increase in dose, 95% CI 1·40–3·62; p=0·0008) and presence of APOE ε4 alleles (HR 2·55 per allele, 95% CI 1·57–4·12; p=0·0001). Interpretation ARIA consist of a spectrum of imaging findings with variable clinical correlates, and some patients with ARIA-E remain asymptomatic even if treatment is continued. The increased risk of ARIA among APOE ε4 carriers, its association with high bapineuzumab dose, and its timecourse in relation to dosing suggest an association between ARIA and alterations in vascular amyloid burden. Funding Elan Corporation, Janssen Alzheimer Immunotherapy, Wyeth Pharmaceuticals, and Pfizer.
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by cerebellar and retinal degeneration, and is caused by a CAG-polyglutamine repeat expansion in ...the
gene. Patients with SCA7 develop progressive cone-rod dystrophy, typically resulting in blindness. Antisense oligonucleotides (ASOs) are single-stranded chemically modified nucleic acids designed to mediate the destruction, prevent the translation, or modify the processing of targeted RNAs. Here, we evaluated ASOs as treatments for SCA7 retinal degeneration in representative mouse models of the disease after injection into the vitreous humor of the eye. Using Ataxin-7 aggregation, visual function, retinal histopathology, gene expression, and epigenetic dysregulation as outcome measures, we found that ASO-mediated Ataxin-7 knockdown yielded improvements in treated SCA7 mice. In SCA7 mice with retinal disease, intravitreal injection of
ASOs also improved visual function despite initiating treatment after symptom onset. Using color fundus photography and autofluorescence imaging, we also determined the nature of retinal degeneration in human SCA7 patients. We observed variable disease severity and cataloged rapidly progressive retinal degeneration. Given the accessibility of neural retina, availability of objective, quantitative readouts for monitoring therapeutic response, and the rapid disease progression in SCA7, ASOs targeting
might represent a viable treatment for SCA7 retinal degeneration.
The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (
) plays a key role in neural development and function.
also includes a protein-coding difference between the ...modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of
Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in
, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species' evolution.
We present new constraints on anisotropic birefringence of the cosmic microwave background polarization using two seasons of data from the Atacama Cosmology Telescope covering 456 square degrees of ...sky. The birefringence power spectrum, measured using a curved-sky quadratic estimator, is consistent with zero. Our results provide the tightest current constraint on birefringence over a range of angular scales between 5 arc minutes and 9°. We improve previous upper limits on the amplitude of a scale-invariant birefringence power spectrum by a factor of between 2 and 3. Assuming a nearly massless axion field during inflation, our result is equivalent to a 2σ upper limit on the Chern-Simons coupling constant between axions and photons of g(αγ)< 4.0 × 10(exp -2)/H(I), where H(I) is the inflationary Hubble scale.
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