Alien Registration- Chouinard, Louis P. (Lewiston, Androscoggin County)

https://digitalmaine.com/alien_docs/29493/thumbnail.jp

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655

Phospholipid class-specific brain enrichment in response to lysophosphatidylcholine docosahexaenoic acid infusion

This project was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) [482597] and from the Canadian Institutes of Health Research (CIHR) [497215] to Dr. R.P. Bazinet and by a NSERC studentship to Dr. C.T. Chen.Peer reviewedPostprin

How should we incentivize private landowners to "produce" more biodiversity?

Globally, much biodiversity is found on private land. Acting to conserve such biodiversity thus requires the design of policies which influence the decision-making of farmers and foresters. In this paper, we outline the economic characteristics of this problem, before reviewing a number of policy options such as conservation auctions and conservation easements. We then discuss a number of policy design problems, such as need for spatial coordination and the choice between paying for outcomes rather than actions, before summarizing what the evidence and theory developed to date tells us about those aspects of biodiversity policy design which need careful attention from policy makers and environmental regulators

The effect of drinking milk containing conjugated linoleic acid on fecal microbiological profile, enzymatic activity, and fecal characteristics in humans

<p>Abstract</p> <p>Background</p> <p>The primary objective was to determine whether consumption of conjugated linoleic acids (CLAs) affected the fecal microbiota composition, fecal enzyme activity or fecal composition.</p> <p>Methods</p> <p>Human subjects consumed (1 <it>L</it>/day) cows' milk (4% fat) containing (5 mg/g fat) <it>cis</it>-9, <it>trans</it>-11 CLA (CONT), (32 mg/g fat) cis-9, <it>trans</it>-11 CLA (NAT) and (32 mg/g fat) <it>trans</it>-10, <it>cis</it>-12 CLA and <it>cis</it>-9, <it>trans</it>-11 CLA (SYN) for 8 weeks, in addition to their normal diet. Milk feeding periods were separated by 4 week washout periods. Fecal samples were obtained at the beginning (day 0) and the end (day 56) of each milk feeding period. Fecal samples were analysed for microbiological profile, enzyme activity, pH and short chain fatty acid content.</p> <p>Results</p> <p>Samples taken at day 0 and day 56 indicated that the numbers of <it>lactobacilli </it>and <it>bifidobacteria </it>significantly decreased after consumption of all experimental milks; total aerobes, total anaerobes, enterobacteria, and enterococci + streptococci did not change. At day 56, the activities of β-glucosidase, nitroreductase, and urease enzymes had decreased compared to samples taken on day 0 for all treatments. β-glucuronidase activity did not change. Fecal pH and ammonia content did not change.</p> <p>Conclusion</p> <p>It was concluded that observed changes could have been attributed to increased milk intake; no differences could be attributed to consumption of the different CLAs.</p

Regional Brain Stem Atrophy in Idiopathic Parkinson's Disease Detected by Anatomical MRI

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia). Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC) matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution) and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3) in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders

Radon backgrounds in the DEAP-1 liquid-argon-based Dark Matter detector

The DEAP-1 \SI{7}{kg} single phase liquid argon scintillation detector was operated underground at SNOLAB in order to test the techniques and measure the backgrounds inherent to single phase detection, in support of the \mbox{DEAP-3600} Dark Matter detector. Backgrounds in DEAP are controlled through material selection, construction techniques, pulse shape discrimination and event reconstruction. This report details the analysis of background events observed in three iterations of the DEAP-1 detector, and the measures taken to reduce them. The $^{222}$Rn decay rate in the liquid argon was measured to be between 16 and \SI{26}{\micro\becquerel\per\kilogram}. We found that the background spectrum near the region of interest for Dark Matter detection in the DEAP-1 detector can be described considering events from three sources: radon daughters decaying on the surface of the active volume, the expected rate of electromagnetic events misidentified as nuclear recoils due to inefficiencies in the pulse shape discrimination, and leakage of events from outside the fiducial volume due to imperfect position reconstruction. These backgrounds statistically account for all observed events, and they will be strongly reduced in the DEAP-3600 detector due to its higher light yield and simpler geometry

Resourcing Scholar-Activism: Collaboration, Transformation, and the Production of Knowledge

In this article we offer a set of resources for scholar-activists to reflect on and guide their practice. We begin by suggesting that research questions should be triangulated to consider not only their scholarly merit but the intellectual and political projects the findings will advance and the research questions of interest to community and social movement collaborators

A review of abnormalities in the perception of visual illusions in schizophrenia

Specific abnormalities of vision in schizophrenia have been observed to affect high-level and some low-level integration mechanisms, suggesting that people with schizophrenia may experience anomalies across different stages in the visual system affecting either early or late processing or both. Here, we review the research into visual illusion perception in schizophrenia and the issues which previous research has faced. One general finding that emerged from the literature is that those with schizophrenia are mostly immune to the effects of high-level illusory displays, but this effect is not consistent across all low-level illusions. The present review suggests that this resistance is due to the weakening of top–down perceptual mechanisms and may be relevant to the understanding of symptoms of visual distortion rather than hallucinations as previously thought