Abstract
Introduction
Narcolepsy type 1 (NT1) is caused by loss of hypocretins, neuropeptides that promote consolidated nocturnal sleep and sustain daytime wakefulness. In mouse models of NT1, sleep ...in the light period is characterized by more brief wake bouts, fewer long wake bouts, and longer REM sleep bouts. It is unknown if this sleep pattern is present in NT1 patients and whether it can distinguish NT1 sleep from other CNS hypersomnia conditions narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH).
Methods
Participants (6-18 years of age, drug -naïve or drug free) had diagnostic PSG/MSLT testing at Boston Children’s Hospital between 2009-2018. PSG records were rescored blinded to diagnosis. We calculated Kaplan Meier survival curves for nocturnal wake and sleep stages extracted from the nocturnal PSGs. To adjust for differences in survival related to age, sex, and race, we used Cox proportional hazards models. In total, we performed survival analysis and compared wake/sleep stages for 4 groups: NT1 (n=46), NT2 (n=12), IH (n=18) and subjective sleepy controls (n=48).
Results
NT1 patients had worse survival of wake bouts compared to controls (p<0.001). In addition, NT1 patients had decreased survival of both NREM 2 and REM sleep bouts compared to all groups (all p<0.001), and, the survival of REM sleep bouts decreased with age (p=0.006). Compared to controls, NREM 2 bouts survived longer in IH patients and whereas NREM 1 bouts survived longer in the NT2 group (p’s<0.006). There were no group effects for NREM 3, but survival of NREM 3 was less in the older IH patients compared to older controls (p<0.02).
Conclusion
Pediatric NT1 patients have unique sleep fragmentation characterized by unstable wake, NREM 2 and REM bouts. Though less severe as NT1, NT2 patients sustain lighter sleep. In contrast, IH patients show overly stable NREM stage 2 sleep and plausibly this contributes to their characteristic sleep inertia. Further research is needed to determine if sleep stability patterns can be used to diagnose CNS hypersomnia conditions and differentiate treatment responsiveness.
Support
K23 National Institutes of Health (NINDS, K23 NS104267-01A1) and Investigator Initiated Research grants from Jazz Pharmaceuticals, Inc. (Dr. Maski)
Category:
Ankle; Basic Sciences/Biologics
Introduction/Purpose:
Extracorporeal shockwave therapy (ESWT) is a non-invasive treatment modality that is utilized in the treatment of chronic Achilles ...tendinopathy (AT).
The purpose of this study was to retrospectively assess outcomes following ESWT for both NAT and IAT at greater than 1-year follow-up, and to identify potential predictors of outcomes.
Methods:
Chart review was conducted to identify patients who underwent ESWT for AT with a minimum of 1-year follow-up. Data collected and assessed included: patient demographics, pathological characteristics, treatment characteristics, Victorian Institute of Sports Assessment-Achilles (VISA-A) and visual analog scale (VAS) scores and failures. Linear regression was performed to identify potential predictors of outcomes. Survival analysis was conducted using Kaplan Meier curves.
Fifty-two cases of IAT and 34 cases of NAT were included. The mean follow-up in the NAT cohort was 22.3±10.2 months and the mean follow-up time in the IAT cohort was 26.8±15.8 months.
Results:
Improvements in VISA-A and VAS scores were observed in the NAT cohort at 6 months follow-up and at final follow-up (p < 0.01). Improvements in VISA-A scores and VAS scores were recorded in the IAT cohort at 6 months follow-up which subsequently deteriorated at final follow-up. In the NAT cohort, the failure rate at 6 months follow-up was 11.8% which increased to 29.4% at final follow-up. In the IAT cohort, the failure rate at 6 months follow-up was 32.7% which increased to 59.6% at final follow-up. Predictors of poor outcomes in the NAT cohort included pre-ESWT subjective clinical score, male, presence of cardiovascular risk factor, and increasing MRI severity. Predictors of poor outcomes in the IAT cohort included pre-ESWT subjective clinical score and increasing MRI severity.
Conclusion:
This study found that superior subjective clinical outcomes together with a lower failure rate maintained over 1 year in the NAT cohort compared to the IAT cohort. This may implicate ESWT as a temporising treatment in IAT and a longer term solution in patients with NAT.
Efforts to identify important risk factors for cognitive impairment and dementia have to date mostly relied on meta-analytic strategies. A comprehensive empirical evaluation of these risk factors ...within a single study is currently lacking.
We used a combined methodology of machine learning and semi-parametric survival analysis to estimate the relative importance of 52 predictors in forecasting cognitive impairment and dementia in a large, population-representative sample of older adults.
Participants from the Health and Retirement Study (N = 9,979; aged 50-98 years) were followed for up to 10 years (M = 6.85 for cognitive impairment; M = 7.67 for dementia). Using a split-sample methodology, we first estimated the relative importance of predictors using machine learning (random forest survival analysis), and we then used semi-parametric survival analysis (Cox proportional hazards) to estimate effect sizes for the most important variables.
African Americans and individuals who scored high on emotional distress were at relatively highest risk for developing cognitive impairment and dementia. Sociodemographic (lower education, Hispanic ethnicity) and health variables (worse subjective health, increasing BMI) were comparatively strong predictors for cognitive impairment. Cardiovascular factors (e.g., smoking, physical inactivity) and polygenic scores (with and without APOEɛ4) appeared less important than expected. Post-hoc sensitivity analyses underscored the robustness of these results.
Higher-order factors (e.g., emotional distress, subjective health), which reflect complex interactions between various aspects of an individual, were more important than narrowly defined factors (e.g., clinical and behavioral indicators) when evaluated concurrently to predict cognitive impairment and dementia.
This study examines the impact of environmental, social, and governance (ESG) reputational risk on a sample of listed firms’ market longevity. Using a novel panel dataset consisting of US firms over ...the period 2007–2019, we perform dynamic empirical analysis to quantify the underlying relationships between firms’ ESG reputational risk and market longevity. We argue that ESG reputational risk has a negative impact on firm growth opportunities, mitigating thus market longevity. The empirical findings survive several robustness checks, providing useful managerial implications for stakeholders and market participants..
Introduced in 2017, the GEPIA (Gene Expression Profiling Interactive Analysis) web server has been a valuable and highly cited resource for gene expression analysis based on tumor and normal samples ...from the TCGA and the GTEx databases. Here, we present GEPIA2, an updated and enhanced version to provide insights with higher resolution and more functionalities. Featuring 198 619 isoforms and 84 cancer subtypes, GEPIA2 has extended gene expression quantification from the gene level to the transcript level, and supports analysis of a specific cancer subtype, and comparison between subtypes. In addition, GEPIA2 has adopted new analysis techniques of gene signature quantification inspired by single-cell sequencing studies, and provides customized analysis where users can upload their own RNA-seq data and compare them with TCGA and GTEx samples. We also offer an API for batch process and easy retrieval of the analysis results. The updated web server is publicly accessible at http://gepia2.cancer-pku.cn/.
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