The Feasibility of a Telehealth Exercise Program Aimed at Increasing Cardiorespiratory Fitness for People After Stroke

Background: Accessing suitable fitness programs post-stroke is difficult for many. The feasibility of telehealth delivery has not been previously reported.Objectives: To assess the feasibility of, and level of satisfaction with home-based telehealth-supervised aerobic exercise training post-stroke.Methods: Twenty-one ambulant participants (?3 months post-stroke) participated in a home-based telehealth-supervised aerobic exercise program (3 d/week, moderate-vigorous intensity, 8-weeks) and provided feedback via questionnaire postintervention. Session details, technical issues, and adverse events were also recorded.Results: Feasibility was high (83% of volunteers met telehealth eligibility criteria, 85% of sessions were conducted by telehealth, and 95% of participants rated usability favourably). Ninety-five percent enjoyed telehealth exercise sessions and would recommend them to others. The preferred telehealth exercise program parameters were: frequency 3 d/week, duration 20-30 min/session, program length 6-12 weeks.Conclusion: The telehealth delivery of exercise sessions to people after stroke appear

Positive correlation between transcriptomic stemness and PI3K/AKT/mTOR signaling scores in breast cancer, and a counterintuitive relationship with PIK3CA genotype

A PI3Kα-selective inhibitor has recently been approved for use in breast tumors harboring mutations in PIK3CA, the gene encoding p110α. Preclinical studies have suggested that the PI3K/AKT/mTOR signaling pathway influences stemness, a dedifferentiation-related cellular phenotype associated with aggressive cancer. However, to date, no direct evidence for such a correlation has been demonstrated in human tumors. In two independent human breast cancer cohorts, encompassing nearly 3,000 tumor samples, transcriptional footprint-based analysis uncovered a positive linear association between transcriptionally-inferred PI3K/AKT/mTOR signaling scores and stemness scores. Unexpectedly, stratification of tumors according to PIK3CA genotype revealed a “biphasic” relationship of mutant PIK3CA allele dosage with these scores. Relative to tumor samples without PIK3CA mutations, the presence of a single copy of a hotspot PIK3CA variant was associated with lower PI3K/AKT/mTOR signaling and stemness scores, whereas the presence of multiple copies of PIK3CA hotspot mutations correlated with higher PI3K/AKT/mTOR signaling and stemness scores. This observation was recapitulated in a human cell model of heterozygous and homozygous PIK3CAH1047R expression. Collectively, our analysis (1) provides evidence for a signaling strength-dependent PI3K-stemness relationship in human breast cancer; (2) supports evaluation of the potential benefit of patient stratification based on a combination of conventional PI3K pathway genetic information with transcriptomic indices of PI3K signaling activation

The Canadian Childhood Nephrotic Syndrome (CHILDNEPH) project: Overview of design and methods

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). Setting: National study, comprised of all 13 Canadian pediatric nephrology clinics. Patients: 400 patients under 18 years of age to be recruited over 2.5 years. Measurements: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. Methods: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Limitations: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Conclusions: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres

The autism inpatient collection: Methods and preliminary sample description

© 2015 Siegel et al. Background: Individuals severely affected by autism spectrum disorder (ASD), including those with intellectual disability, expressive language impairment, and/or self-injurious behavior (SIB), are underrepresented in the ASD literature and extant collections of phenotypic and biological data. An understanding of ASD's etiology and subtypes can only be as complete as the studied samples are representative. Methods: The Autism Inpatient Collection (AIC) is a multi-site study enrolling children and adolescents with ASD aged 4-20 years admitted to six specialized inpatient psychiatry units. Enrollment began March, 2014, and continues at a rate of over 400 children annually. Measures characterizing adaptive and cognitive functioning, communication, externalizing behaviors, emotion regulation, psychiatric co-morbidity, self-injurious behavior, parent stress, and parent self-efficacy are collected. ASD diagnosis is confirmed by the Autism Diagnostic Observation Schedule - 2 (ADOS-2) and extensive inpatient observation. Biological samples from probands and their biological parents are banked and processed for DNA extraction and creation of lymphoblastoid cell lines. Results: Sixty-one percent of eligible subjects were enrolled. The first 147 subjects were an average of 12.6 years old (SD 3.42, range 4-20); 26.5 % female; 74.8 % Caucasian, and 81.6 % non-Hispanic/non-Latino. Mean non-verbal intelligence quotient IQ = 70.9 (SD 29.16, range 30-137) and mean adaptive behavior composite score = 55.6 (SD 12.9, range 27-96). A majority of subjects (52.4 %) were non- or minimally verbal. The average Aberrant Behavior Checklist - Irritability Subscale score was 28.6, well above the typical threshold for clinically concerning externalizing behaviors, and 26.5 % of the sample engaged in SIB. Females had more frequent and severe SIB than males. Conclusions: Preliminary data indicate that the AIC has a rich representation of the portion of the autism spectrum that is understudied and underrepresented in extant data collections. More than half of the sample is non- or minimally verbal, over 40 % have intellectual disability, and over one quarter exhibit SIB. The AIC is a substantial new resource for study of the full autism spectrum, which will augment existing data on higher-functioning cohorts and facilitate the identification of genetic subtypes and novel treatment targets. The AIC investigators welcome collaborations with other investigators, and access to the AIC phenotypic data and biosamples may be requested through the Simons Foundation (www.sfari.org)

The Influence of Perpetrator Exposure Time and Weapon Presence/Timing on Eyewitness Confidence and Accuracy

Crimes can occur in a matter of seconds, with little time available for an eyewitness to encode a perpetrator’s face. The presence of a weapon can further exacerbate this situation. Few studies have featured mock crimes of short duration, especially with a weapon manipulation. We conducted an experiment to investigate the impact of weapon presence and short perpetrator exposure times (3 versus 10 s) on eyewitness confidence and accuracy. We found that recall concerning the perpetrator was worse when a weapon was present, replicating the weapon focus effect. However, there was no effect on eyewitness identification accuracy. Calibration analyses revealed that all conditions produced a strong confidence-accuracy relationship. Confidence- Accuracy Characteristic curves illustrated almost perfect accuracy for suspect identifications at the highest levels of confidence. We conclude that weapon presence during a brief crime does not necessarily result in negative consequences for either eyewitness identification accuracy or the confidence-accuracy relationship

Invisible Diaspora?:English Ethnicity in the United States before 1920

The article presents an examination into the English population of the United States during the 19th and early 20th centuries, examining their ethnic identity as a diaspora community. Introductory details are given noting the relative lack of attention given to English Americans as an ethnic group. Topics addressed include reasons behind the invisibility of the English immigrant identity in the U.S., the existence of English ethnic organizations, and an overview of their activities

Human TFIIH Kinase CDK7 Regulates Transcription-Associated Chromatin Modifications.

CDK7 phosphorylates the RNA polymerase II (pol II) C-terminal domain CTD and activates the P-TEFb-associated kinase CDK9, but its regulatory roles remain obscure. Here, using human CDK7 analog-sensitive (CDK7as) cells, we observed reduced capping enzyme recruitment, increased pol II promoter-proximal pausing, and defective termination at gene 3' ends upon CDK7 inhibition. We also noted that CDK7 regulates chromatin modifications downstream of transcription start sites. H3K4me3 spreading was restricted at gene 5' ends and H3K36me3 was displaced toward gene 3' ends in CDK7as cells. Mass spectrometry identified factors that bound TFIIH-phosphorylated versus P-TEFb-phosphorylated CTD (versus unmodified); capping enzymes and H3K4 methyltransferase complexes, SETD1A/B, selectively bound phosphorylated CTD, and the H3K36 methyltransferase SETD2 specifically bound P-TEFb-phosphorylated CTD. Moreover, TFIIH-phosphorylated CTD stimulated SETD1A/B activity toward nucleosomes, revealing a mechanistic basis for CDK7 regulation of H3K4me3 spreading. Collectively, these results implicate a CDK7-dependent "CTD code" that regulates chromatin marks in addition to RNA processing and pol II pausing

Marine pelagic ecosystems: the West Antarctic Peninsula

The marine ecosystem of the West Antarctic Peninsula (WAP) extends from the Bellingshausen Sea to the northern tip of the peninsula and from the mostly glaciated coast across the continental shelf to the shelf break in the west. The glacially sculpted coastline along the peninsula is highly convoluted and characterized by deep embayments that are often interconnected by channels that facilitate transport of heat and nutrients into the shelf domain. The ecosystem is divided into three subregions, the continental slope, shelf and coastal regions, each with unique ocean dynamics, water mass and biological distributions. The WAP shelf lies within the Antarctic Sea Ice Zone (SIZ) and like other SIZs, the WAP system is very productive, supporting large stocks of marine mammals, birds and the Antarctic krill, Euphausia superba. Ecosystem dynamics is dominated by the seasonal and interannual variation in sea ice extent and retreat. The Antarctic Peninsula is one among the most rapidly warming regions on Earth, having experienced a 28C increase in the annual mean temperature and a 68C rise in the mean winter temperature since 1950. Delivery of heat from the Antarctic Circumpolar Current has increased significantly in the past decade, sufficient to drive to a 0.68C warming of the upper 300 m of shelf water. In the past 50 years and continuing in the twenty-first century, the warm, moist maritime climate of the northern WAP has been migrating south, displacing the once dominant cold, dry continental Antarctic climate and causing multi-level responses in the marine ecosystem. Ecosystem responses to the regional warming include increased heat transport, decreased sea ice extent and duration, local declines in icedependent Ade´lie penguins, increase in ice-tolerant gentoo and chinstrap penguins, alterations in phytoplankton and zooplankton community composition and changes in krill recruitment, abundance and availability to predators. The climate/ecological gradients extending along theWAPand the presence of monitoring systems, field stations and long-term research programmes make the region an invaluable observatory of climate change and marine ecosystem response

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

Background: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.Objective: To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159).Methods and Findings: Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B₆ and B₁₂ in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B₁₂ (0.5 mg/d) and vitamin B₆ (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.Results: A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63-0.90] in the active treatment group and 1.08% [0.94-1.22] in the placebo group (P=0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine &gt; 13μmol/L was 53% lower in the active treatment group (P=0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.Conclusions and significance: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease.</p