Related Services for Vermont\u27s Students with Disabilities

The purpose of Related Services for Vermont’s Students with Disabilities is to offer information regarding related services that is consistent with IDEA and with Vermont Law and regulations. It also describes promising or exemplary practices in education, special education, and related services. The manual’s content applies to all related services disciplines which serve students with disabilities, ages 3 through 21, who have an Individualized Education Program (IEP)

Frailty: A global measure of the multisystem impact of COPD

Chronic obstructive pulmonary disease (COPD) is a multisystem disease that resembles the accumulation of multiple impairments seen in aging. A comprehensive geriatric assessment (CGA) captures multisystem deficits, from which a frailty index (FI) can be derived. We hypothesized that patients with COPD would be frailer than a comparator group free from respiratory disease. In this cross-sectional analysis, the CGA questionnaire was completed and used to derive an FI in 520 patients diagnosed with COPD and 150 comparators. All subjects were assessed for lung function, body composition, 6-minute walking distance (6MWD), and handgrip strength. Patients completed validated questionnaires on health-related quality of life and respiratory symptoms. Patients and comparators were similar in age, gender, and body mass index, but patients had a greater mean ± SD FI 0.16 ± 0.08 than comparators 0.05 ± 0.03. In patients, a stepwise linear regression 6MWD (β = −0.43), number of comorbidities (β = −0.38), handgrip (β = −0.11), and number of exacerbations (β = 0.11) were predictors of frailty (all p < 0.01). This large study suggests patients with COPD are frailer than comparators. The FI derived from the CGA captures the deterioration of multiple systems in COPD and provides an overview of impairments, which may identify individuals at increased risk of morbidity and mortality in COPD

Final countdown for biodiversity hotspots

Most of Earth's biodiversity is found in 36 biodiversity hotspots, yet less than 10% natural intact vegetation remains. We calculated models projecting the future state of most of these hotspots for the year 2050, based on future climatic and agroeconomic pressure. Our models project an increasing demand for agricultural land resulting in the conversion of >50% of remaining natural intact vegetation in about one third of all hotspots, and in 2-6 hotspots resulting from climatic pressure. This confirms that, in the short term, habitat loss is of greater concern than climate change for hotspots and their biodiversity. Hotspots are most severely threatened in tropical Africa and parts of Asia, where demographic pressure and the demand for agricultural land is highest. The speed and magnitude of pristine habitat loss is, according to our models, much greater than previously shown when combining both scenarios on future climatic and agroeconomic pressure

Plasma Dynamics

Contains reports on six research projects.National Science Foundation (Grant ECS82-00646)National Science Foundation (Grant ECS82-13485)U.S. Air Force - Office of Scientific Research (Contract F33615-81-K-1426)U.S. Air Force - Office of Scientific Research (Contract F49620-83-C-0008)U.S. Air Force - Office of Scientific Research (Contract AFOSR-84-0026)U.S. Navy - Office of Naval Research (Contract N00014-83-K-2024)Sandia National Laboratory (Contract 31-5606)Sandia National Laboratory (Contract 48-5725)U.S. Department of Energy (Contract DE-ACO2-78ET-51013)National Science Foundation (Grant ECS82-13430

Insights into olfactory ensheathing cell development from a laser-microdissection and transcriptome-profiling approach.

Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridization, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific (that is, not expressed by Schwann cells). One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.Cambridge Commonwealth Trust Cambridge Philosophical Societ

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change &#8805;2) and significantly altered in GBM (p &#8804; 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case-control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORshighest vs. lowest tertile > 6.0 (Bonferroni-corrected P-values < 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition