“Even a little bit of independence can go a long way”: The experiences of students with disabilities transitioning from high school to college

According to the National Center for Education Statistics (2020), the national percentage of first-time, full-time college students who returned to the same campus the following year was 81%. For students with disabilities, retention and graduation statistics were disproportionate to their non-disabled peers. Students with disabilities graduated high school at a rate of 73% in 2018 (NCES, 2020) but completed college programs at a rate of just 38% while their non-disabled peers graduated at a rate of 51% (Sanford et al., 2011). Additionally, students were less likely to be full time students and were less likely to graduate on time (Lee, Rojewski, Gregg, & Jeong, 2014). In order to understand why so many college-bound students with disabilities are failing to complete post-secondary programs or participate in the typical college experience I conducted interviews to explore the experiences of students with disabilities who have transitioned from high school to college. The intent of this qualitative study was to utilize these interviews to explore the experiences of students with disabilities who have made the transition from high school to college and gain insight into how students with disabilities, parents, and Intervention Specialists could better prepare for a successful transition from high school to college, and how colleges might better serve students with disabilities while they are enrolled. Findings: Interviews with participants revealed two major themes: Challenges and Supports. Interestingly, there was not a consensus among participants about these challenges and supports. Some participants had great difficulty in areas that came easily for others. This aligns with the individualized nature of special education that participants experienced in high school. Data was further organized into five sub-themes; Identifying Disabilities, Needs and Supports, Interacting with Faculty and Staff, Navigating Campus, and Wraparound Services

Assessment of neighborhood poverty, cognitive function, and prefrontal and hippocampal volumes in children

Importance: The association between poverty and unfavorable cognitive outcomes is robust, but most research has focused on individual household socioeconomic status (SES). There is increasing evidence that neighborhood context explains unique variance not accounted for by household SES. Objective: To evaluate whether neighborhood poverty (NP) is associated with cognitive function and prefrontal and hippocampal brain structure in ways that are dissociable from household SES. Design, Setting, and Participants: This cross-sectional study used a baseline sample of the ongoing longitudinal Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study will follow participants for assessments each year for 10 years. Data were collected at 21 US sites, mostly within urban and suburban areas, between September 2019 and October 2018. School-based recruitment was used to create a participant sample reflecting the US population. Data analysis was conducted from March to June 2019. Main Outcomes and Measures: NP and household SES were included as factors potentially associated with National Institutes of Health Toolbox Cognitive Battery subtests and hippocampal and prefrontal (dorsolateral prefrontal cortex [DLPFC], dorsomedial PFC [DMPFC], superior frontal gyrus [SFG]) volumes. Independent variables were first considered individually and then together in mixed-effects models with age, sex, and intracranial volume as covariates. Structural equation modeling (SEM) was used to assess shared variance in NP to brain structure and cognitive task associations. The tested hypotheses were formulated after data collection. Results: A total of 11 875 children aged 9 and 10 years (5678 [47.8%] girls) were analyzed. Greater NP was associated with lower scores across all cognitive domains (eg, total composite: β = -0.18; 95% CI, -0.21 to -0.15; P \u3c .001) and with decreased brain volume in the DLPFC (eg, right DLPFC: β = -0.09; 95% CI, -0.12 to -0.07; P \u3c .001), DMPFC (eg, right DMPC: β = -0.07; 95% CI, -0.09 to -0.05; P \u3c .001), SFG (eg, right SFG: β = -0.05; 95% CI, -0.08 to -0.03; P \u3c .001), and right hippocampus (β = -0.04; 95% CI, -0.06 to -0.01; P = .01), even when accounting for household income. Greater household income was associated with higher scores across all cognitive domains (eg, total composite: β = 0.30; 95% CI, 0.28 to 0.33; P \u3c .001) and larger volume in all prefrontal and hippocampal brain regions (eg, right hippocampus: β = 0.04; 95% CI, 0.02 to 0.07; P \u3c .001) even when accounting for NP. The SEM model was a good fit across all cognitive domains, with prefrontal regions being associated with NP relations to language (picture vocabulary: estimate [SE], -0.03 [0.01]; P \u3c .001; oral reading: estimate [SE], -0.02 [0.01]; P \u3c .001), episodic memory (picture sequence: estimate [SE], -0.02 [0.01]; P = .008), and working memory (dimensional card sort: estimate [SE], -0.02 [0.01]; P = .001; flanker inhibitory control: estimate [SE], -0.01 [0.01]; P = .01; list sorting: estimate [SE], -0.03 [0.01]; P \u3c .001) and hippocampal regions being associated with NP associations with language (picture vocabulary: estimate [SE], -0.01 [0.004]; P \u3c .001) and episodic memory (picture sequence: estimate [SE], -0.01 [0.004]; P \u3c 0.001). Conclusions and Relevance: In this study, NP accounted for unique variance in cognitive function and prefrontal and right hippocampal brain volume. These findings demonstrate the importance of including broader environmental influences when conceptualizing early life adversity

Investigation of the metabolism of Substance-P at the blood-brain barrier using LC-MS/MS

Please note that this is an author-produced PDF of an article accepted for publication following peer review. The publisher version is available on its site.Substance P (SP) has been associated with pain, depression as well as neurodegenerative diseases. Many of these diverse actions of SP can potentially be attributed to SP metabolites generated at the blood-brain barrier (BBB). In these studies, the metabolism of SP was investigated using an in vitro model of the BBB and LC-MS/MS. Substance P metabolism was found to be non-saturable in the concentration range of 100 nM to 10 μM, with approximately 70% of the peptide remaining intact after 5 hrs. The major metabolites of SP were identified by MS to be 3-11 and 5-11. Two previously unreported metabolites, 5-11 and 6-11 were also found in our studies. Several additional minor SP metabolites including 1-9 and 2-11 were also identified. A profile of the SP metabolites generated by the BBB overtime was obtained. The results from the present study provide us a better understanding of the role of blood-brain barrier in the pharmacology of SP

Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures

Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln

Self-Reported Sleep Apnea and Dementia Risk: Findings from the Prevention of Alzheimer\u27s Disease with Vitamin E and Selenium Trial

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer\u27s Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status. DESIGN: Secondary analysis based on data collected during PREADViSE. SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location. PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = 7,547). MEASUREMENTS: Participants were interviewed at baseline for sleep apnea. The Memory Impairment Screen (MIS) was administered to each participant annually. Subjects who failed this initial screen were tested with secondary screening tests. Medical history and medication use were determined, and the AD8 dementia screening instrument was used. RESULTS: The effect of self-reported sleep apnea on dementia risk depended on APOE ɛ4 status. When the allele was absent, baseline self-reported sleep apnea was associated with a 66% higher risk of developing dementia (95% confidence interval = 2-170%), whereas self-reported sleep apnea conferred no additional risk for participants with an ɛ4 allele. CONCLUSION: Sleep apnea may increase risk of dementia in the absence of APOE ɛ4. This may help inform prevention strategies for dementia or AD in older men with sleep apnea. Registration: PREADViSE is registered at ClinicalTrials.gov: NCT00040378

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion.

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance

Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures

Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1(−/−)) that simultaneously exhibits neuroinflammation, neurodegeneration, and spontaneous seizures. Proteomic analysis showed that putative CBD receptors are expressed at similar levels in the brains of Cln1(−/−) mice compared to normal animals. Cln1(−/−) mice received an oral dose (100 mg/kg/day) of CBD for six months and were evaluated for changes in pathological markers of disease and seizures. Chronic cannabidiol administration was well-tolerated, high levels of CBD were detected in the brain, and markers of astrocytosis and microgliosis were reduced. However, CBD had no apparent effect on seizure frequency or neuron survival. These data are consistent with CBD having immunomodulatory effects. It is possible that a higher dose of CBD could also reduce neurodegeneration and seizure frequency

The Response to a Perturbation in the Reflection Amplitude

We apply inverse scattering theory to calculate the functional derivative of the potential $V(x)$ and wave function $\psi(x,k)$ of a one-dimensional Schr\"odinger operator with respect to the reflection amplitude $r(k)$.Comment: 16 pages, no figure