Alexandrium cyst distribution and germination in Puget Sound

The Puget Sound Alexandrium Harmful Algal Bloom (PS-AHAB: www.tiny.cc/psahab) program, funded by NOAA/ECOHAB, seeks to understand environmental controls on the benthic (cyst) and planktonic life stages of the toxic dinoflagellate Alexandrium catenella, and disentangle the effects of climate pathways on the timing and location of blooms. Spatially detailed mapping of winter surface sediment cyst distributions in 2011, 2012, and 2013 found the highest cyst concentrations in Bellingham Bay in the north and Quartermaster Harbor in central Puget Sound. However, the viability of cysts at these seed bed areas is low – with fewer than 54% of cysts germinating when incubated at favorable temperatures. The time of year that cysts can germinate does not appear to be controlled by an endogenous clock, but the rate of germination is strongly determined by temperature. These results may complicate potential relationships between cyst abundances and bloom magnitude the following season. A monthly time series of cyst abundances was also collected at two locations in Quartermaster Harbor from 2012-2013 as part of a related Sea Grant project investigating the seasonal variability in cyst abundances. Cyst abundances varied by a factor of ~6 with the lowest cyst abundances occurring in the spring (Apr) and the highest cyst abundances occurring in late fall (Oct/Nov). This seasonal pattern is consistent with observed A. catenella bloom dynamics in Quartermaster Harbor. The improved understanding of the processes that govern cyst germination and bloom initiation provided by this study contribute towards the development of a predictive capacity for A. catenella blooms in Puget Sound. Details on A. catenella growth rates and toxicity and an analysis of potential bloom transport using a high-resolution hydrodynamic simulation of Puget Sound and adjacent coastal waters (MoSSea: http://faculty.washington.edu/pmacc/MoSSea/), as well as simulations of potential future climate impacts on blooms, will be discussed in separate presentations by B.D. Bill and S.K. Moore respectively, at this conference

Ontario’s stroke report cards: Cross-continuum data linkage allows evaluation of system of care

Introduction Report cards or scorecards typically reflect one particular sector along the care continuum; however, stroke patients typically require acute care, inpatient rehabilitation and community care highlighting the need to link data sources to demonstrate the interdependencies between and across sectors. Objectives and Approach 1) Identify stroke best practice indicators from across the care continuum; 2) develop a one page report card that reports on the quality of the stroke system of care through data linkage and 3) visually impactful knowledge translation tool. The indicators cover five health care sectors starting with pre-hospital stroke symptom onset, then to management of the acute event, to institutional and community-based rehabilitative care, reintegration into the community and secondary prevention. The report card is a knowledge translation tool that identifies gaps in best practice, provides achievable benchmarks of regional and provincial stroke system performance to drive system change. Results Using data linkage techniques, seven administrative datasets are used to populate the 20 indicators in the annual Ontario stroke report card. Indicator performance was trended by comparing the previous 3 years’ results to the most recent year of data. Fifteen of 17 indicators improved (11 statistically significant) compared to the previous three years and 2 indicators did not change / declined. Performance benchmarks were calculated using Achievable Benchmarks of Care™ methodology and 14 of 16 performance benchmarks improved since 2014/15. There was wide variation across indicators with only 4 indicators showing a reduction in regional variation. The Ontario stroke report card can be viewed at https://www.ices.on.ca/Publications/Atlases-and-Reports/2017/Stroke-Report-Cards. Conclusion/Implications The Ontario stroke report card spans the stroke care continuum, provides a snapshot of Ontario’s stroke system performance. Data linkage is essential for a system-wide opportunity to evaluate and influence system performance. This cross-continuum approach and report card format could be applied to other health related conditions

Neural stem cell isolation from the whole mouse brain using the novel FABP7-binding fluorescent dye, CDr3

10.1016/j.scr.2013.09.002Stem Cell Research1131314-132

MicroRNA-221 Modulates RSV Replication in Human Bronchial Epithelium by Targeting NGF Expression

Background: Early-life infection by respiratory syncytial virus (RSV) is associated with aberrant expression of the prototypical neurotrophin nerve growth factor (NGF) and its cognate receptors in human bronchial epithelium. However, the chain of events leading to this outcome, and its functional implications for the progression of the viral infection, has not been elucidated. This study sought to test the hypothesis that RSV infection modulates neurotrophic pathways in human airways by silencing the expression of specific microRNAs (miRNAs), and that this effect favors viral growth by interfering with programmed death of infected cells. Methodology: Human bronchial epithelial cells infected with green fluorescent protein-expressing RSV (rgRSV) were screened with multiplex qPCR arrays, and miRNAs significantly affected by the virus were analyzed for homology with mRNAs encoding neurotrophic factors or receptors. Mimic sequences of selected miRNAs were transfected into noninfected bronchial cells to confirm the role of each of them in regulating neurotrophins expression at the gene and protein level, and to study their influence on cell cycle and viral replication. Principal Findings: RSV caused downregulation of 24 miRNAs and upregulation of 2 (p,0.01). Homology analysis of microarray data revealed that 6 of those miRNAs exhibited a high degree of complementarity to NGF and/or one of its cognate receptors TrKA and p75 NTR. Among the selected miRNAs, miR-221 was significantly downregulated by RSV and it

PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression

Sample and data collection were funded by Cancer Research UK. Analysis was funded by Breast Cancer Now, the Rosetrees Trust, Guys & St Thomas’ Charity (CanHelp) and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

A novel carbon-fibre adjustable reusable accessory (CARA) for supine breast positioning to reduce toxicity in breast adjuvant radiotherapy: a study protocol for a multicentre phase III randomized controlled trial

Background A novel device for supine positioning in breast radiotherapy for patients with large or pendulous breasts has been developed and tested in phase II studies. This trial is designed to assess the efficacy of the device to reduce skin toxicity and unwanted normal tissue dose in comparison to the current clinical standard for supine breast support during breast radiotherapy. Methods Patients at high risk for moist desquamation, having infra-mammary fold or lateral ptosis, will be randomized into two arms. Patients in the control arm will receive breast radiotherapy with supine positioning using current standard of care. Patients in the experimental arm will be positioned supine with the novel device. The primary endpoint is the incidence of moist desquamation in the infra-mammary fold. We hypothesize a 20% reduction (from 50 to 30%) in the rate of moist desquamation in the study arm versus the control arm. For 80% power, two-tailed α = 0.05 and 10% loss to follow up, 110 patients will be assigned to each arm. The proportion of patients experiencing moist desquamation in the two arms will be compared using logistic regression adjusting for brassiere cup size, skin fold size, body mass index, smoking status, and dose fractionation schedule. An unadjusted comparison will also be made using the chi-square test, or Fisher’s exact test, if appropriate. Secondary endpoints include dose-volume statistics for the lung and heart, skin dose and clinical parameters including setup time, reproducibility, and staff experience with setup procedures. Patient-reported pain, skin condition interference with sleep and daily activities, and comfort during treatment are also secondary endpoints. Discussion Based on results from earlier phase II studies, it is expected that the device-enabled elimination of infra-mammary fold should reduce toxicity and improve quality of life for this patient population. Earlier studies showed reduction in dose to organs at risk including lung and heart, indicating potential for other long-term benefits for patients using the device. This study is limited to acute skin toxicity, patient-reported outcomes, and clinical factors to inform integration of the device into standard breast radiotherapy procedures. Trial registration Clinicaltrials.gov identifier: NCT04257396 . Registered February 6 2020.Medicine, Faculty ofScience, Faculty ofNon UBCPhysics and Astronomy, Department ofPopulation and Public Health (SPPH), School ofSurgery, Department ofReviewedFacultyResearche