158 research outputs found
Managing Flexible Loads in Residential Areas
Load flexibility in households is a promising option for efficient and reliable operation of future power systems. Due to the distributed nature of residential demand, coordination mechanisms have to cope with a large number of flexible units. This thesis provides a model for demand response analysis and proposes different mechanisms for coordinating flexible loads. In particular, the potential to match intermittent output of renewable generators with electricity demand is investigated
Letters to Lindbergh: An Illustrated Childrenâs Book
Letters to Lindbergh is an illustrated childrenâs book offering a new perspective on the relationship between the aviator Charles Lindbergh and his father, while also bringing a visual component to historical documents. Illustrated by Samantha Gottwalt, the bookâs art explores collage media techniques and the story is told through letters that Lindbergh exchanged with his father during his adolescence (1909-1924.) It aims to explore a facet of Lindberghâs life that has little exposure and invited the reader to step into a vividly colored collaged world created with paint and cut paper. Through the new perspective of Lindberghâs correspondence the story intends to inspire and offers a creative solution for historical storytelling, while introducing young readers to the boy who would become one of the most famous and influential people of the 20th Century.
Client Views About Length of Medicated Assisted Therapy for Opioid Use Disorder
Opioid addiction has been on the rise since 1990, when physicians began administering prescription pain medications. The population has undergone a drastic change from opioid prescriptions such as oxycodone to illicit forms, such as heroin, to aid pain management. Illegal opiates became the alternative drug at a lower cost to fulfill cravings and dependence that prescriptions may no longer feed. With a rise in dependence, pharmaceutical laboratories developed medicated assistant treatments (MAT) to aid in this crisis, more formally known as buprenorphine and methadone. Studies conducted show evidence of a decrease in illicit opioid use when using these medicated treatments and can lead to successful retention of the addiction. The users\u27 experiences are often overlooked in terms of how administration occurs and when the taper of these therapies begins. Anecdotal findings suggest that prescribers continue to prescribe medications with intended harm reduction approaches instead of focusing on abstinence. This study focuses on the history of opioid prescription, addiction, and medical information regarding medication therapy, harm reduction, and the deliverance of why persons administered MAT has been prescribed for an extended amount of time. This study focuses on who is primarily responsible for the length of MAT treatment. Interviews with persons previously or currently prescribed medication-assisted treatment will initiate personal experiences to conclude whether the client or physician controls MAT administration length. Recommendations of participants will be discussed regarding their opinions on the length of treatment
Suggestions for a new look at the lamellar-vacuolar field or "Golgi complex" and their pattern of lower parts
Every cytologist in biology or medicine knows the so-called "Golgi-Complex", but no cytologist can state exactly the structure and the function of this complex. Nevertheless, in the last six years this" Golgi complex" in about 100 different cells has been seen in the electron microscope. That is the reason I have tried to make a comparative study of these fields. I would like to give a
short review of this investigation here, having been kindly invited by Prof. S. SENO.</p
Quantification of the Time Course of CYP3A Inhibition, Activation, and Induction Using a Population Pharmacokinetic Model of Microdosed Midazolam Continuous Infusion
Background
Cytochrome P450 (CYP) 3A contributes to the metabolism of many approved drugs. CYP3A perpetrator drugs can profoundly alter the exposure of CYP3A substrates. However, effects of such drug-drug interactions are usually reported as maximum effects rather than studied as time-dependent processes. Identification of the time course of CYP3A modulation can provide insight into when significant changes to CYP3A activity occurs, help better design drug-drug interaction studies, and manage drug-drug interactions in clinical practice.
Objective
We aimed to quantify the time course and extent of the in vivo modulation of different CYP3A perpetrator drugs on hepatic CYP3A activity and distinguish different modulatory mechanisms by their time of onset, using pharmacologically inactive intravenous microgram doses of the CYP3A-specific substrate midazolam, as a marker of CYP3A activity.
Methods
Twenty-four healthy individuals received an intravenous midazolam bolus followed by a continuous infusion for 10 or 36 h. Individuals were randomized into four arms: within each arm, two individuals served as a placebo control and, 2 h after start of the midazolam infusion, four individuals received the CYP3A perpetrator drug: voriconazole (inhibitor, orally or intravenously), rifampicin (inducer, orally), or efavirenz (activator, orally). After midazolam bolus administration, blood samples were taken every hour (rifampicin arm) or every 15 min (remaining study arms) until the end of midazolam infusion. A total of 1858 concentrations were equally divided between midazolam and its metabolite, 1â-hydroxymidazolam. A nonlinear mixed-effects population pharmacokinetic model of both compounds was developed using NONMEMÂź. CYP3A activity modulation was quantified over time, as the relative change of midazolam clearance encountered by the perpetrator drug, compared to the corresponding clearance value in the placebo arm.
Results
Time course of CYP3A modulation and magnitude of maximum effect were identified for each perpetrator drug. While efavirenz CYP3A activation was relatively fast and short, reaching a maximum after approximately 2â3 h, the induction effect of rifampicin could only be observed after 22 h, with a maximum after approximately 28â30 h followed by a steep drop to almost baseline within 1â2 h. In contrast, the inhibitory impact of both oral and intravenous voriconazole was prolonged with a steady inhibition of CYP3A activity followed by a gradual increase in the inhibitory effect until the end of sampling at 8 h. Relative maximum clearance changes were +59.1%, +46.7%, â70.6%, and â61.1% for efavirenz, rifampicin, oral voriconazole, and intravenous voriconazole, respectively.
Conclusions
We could distinguish between different mechanisms of CYP3A modulation by the time of onset. Identification of the time at which clearance significantly changes, per perpetrator drug, can guide the design of an optimal sampling schedule for future drug-drug interaction studies. The impact of a short-term combination of different perpetrator drugs on the paradigm CYP3A substrate midazolam was characterized and can define combination intervals in which no relevant interaction is to be expected.
Clinical Trial Registration
The trial was registered at the European Union Drug Regulating Authorities for Clinical Trials (EudraCT-No. 2013-004869-14)
Combination adherence strategy to support HIV antiretroviral therapy and pre-exposure prophylaxis adherence during pregnancy and breastfeeding: protocol for a pair of pilot randomised trials.
INTRODUCTION
To realise the expected gains from prevention of mother-to-child HIV transmission initiatives, adherence to preventative and therapeutic antiretroviral regimens is critical and interventions deployable in busy programmatic settings with a high HIV burden are needed. Based on formative research, we developed an approach that integrates patient-centred counselling and engagement of an adherence supporter for pregnant and breastfeeding women initiating HIV treatment (ie, antiretroviral therapy (ART)) or biomedical HIV prevention (ie, pre-exposure prophylaxis (PrEP)).
METHODS
Tonse Pamodzi 2 is a pilot study designed to provide acceptability, fidelity and clinical outcomes data on a set of behavioural interventions for adherence support. The study comprises two parallel randomised trials, enrolling HIV-positive pregnant women initiating ART (Trial 1, n=100) and HIV-negative pregnant women with risk of HIV acquisition and willing to initiate PrEP (Trial 2, n=200). Within each trial, participants are randomised 1:1 to either the intervention or control group. The Tonse Pamodzi adherence intervention comprises patient-centred counselling (adapted Integrated Next Step Counseling(iNSC)) and external adherence support tailored to the clinical context (ie, for ART or PrEP). Participants randomly assigned to the control group receive standard counselling based on local HIV guidelines. Participants are followed for 6âmonths. To assess intervention acceptability, we will employ a mixed method approach to describe participant engagement, satisfaction, and discussion content. We will audit and score recorded counselling sessions to evaluate the implementation fidelity of iNSC sessions. We will also assess clinical outcomes at 3 and 6âmonths for both Trial 1 (retention in care and viral suppression of HIV) and Trial 2 (retention in care, and plasma and intracellular tenofovir drug concentrations).
ETHICS AND DISSEMINATION
The study protocol was approved by the Malawi National Health Science Research Committee (19/05/2334) and the University of North Carolina at Chapel Hill Institutional Review Board (19-1060).
TRIAL REGISTRATION NUMBER
NCT04330989
Concept and benchmark results for Big Data energy forecasting based on Apache Spark
The present article describes a concept for the creation and application of energy forecasting models in a distributed environment. Additionally, a benchmark comparing the time required for the training and application of data-driven forecasting models on a single computer and a computing cluster is presented. This comparison is based on a simulated dataset and both R and Apache Spark are used. Furthermore, the obtained results show certain points in which the utilization of distributed computing based on Spark may be advantageous
Die Weiterentwicklung der Energiewirtschaft in Baden-WĂŒrttemberg bis 2025 unter BerĂŒcksichtigung der Liefer- und Preissicherheit : im Auftrag des Baden-WĂŒrttembergischen Industrie- und Handelskammertags ; Aktualisierung Januar 2016
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