Gene by Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

Chronic cocaine use has been associated with structural deficits in brain regions having dopamine receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. We therefore examined variations in gray matter volume (GMV) as a function of lifetime drug use and the monoamine oxidase A (MAOA) genotype in cocaine use disorders (CUD) and healthy controls

Role of nucleus accumbens core but not shell in incubation of methamphetamine craving after voluntary abstinence

We recently introduced an animal model to study incubation of drug craving after prolonged voluntary abstinence, mimicking the human condition of relapse after successful contingency management treatment. Here we studied the role of the nucleus accumbens (NAc) in this model. We trained rats to self-administer a palatable solution (sucrose+maltodextrin 1%, 6 h/day, 6 days) and methamphetamine (6 h/day, 12 days). We then evaluated relapse to methamphetamine seeking after 1 and 15 days of voluntary abstinence, achieved via a discrete choice procedure between the palatable solution and methamphetamine (14 days). We used RNAscope in-situ hybridization to quantify the co-labeling of the neuronal activity marker Fos, and dopamine Drd1- and Drd2-expressing medium spiny neurons (MSNs) in NAc core and shell during the incubation tests. Next, we determined the effect of pharmacological inactivation of NAc core and shell by either GABAA and GABAB agonists (muscimol+baclofen, 50+50 ng/side), Drd1-Drd2 antagonist (flupenthixol, 10 µg/side) or the selective Drd1 or Drd2 antagonists (SCH39166 1.0 µg/side or raclopride 1.0 µg/side) during the relapse tests. Incubated methamphetamine seeking after voluntary abstinence was associated with a selective increase of Fos expression in the NAc core, but not shell, and Fos was co-labeled with both Drd1- and Drd2-MSNs. NAc core, but not shell, injections of muscimol+baclofen, flupenthixol, SCH39166, and raclopride reduced methamphetamine seeking after 15 days of abstinence. Together, our results suggest that dopamine transmission through Drd1 and Drd2 in NAc core is critical to the incubation of methamphetamine craving after voluntary abstinence

Valuing Health Gain from Composite Response Endpoints for Multisystem Diseases

Objectives: This study aimed to demonstrate how to estimate the value of health gain after patients with a multisystem disease achieve a condition-specific composite response endpoint. Methods: Data from patients treated in routine practice with an exemplar multisystem disease (systemic lupus erythematosus) were extracted from a national register (British Isles Lupus Assessment Group Biologics Register). Two bespoke composite response endpoints (Major Clinical Response and Improvement) were developed in advance of this study. Difference-in-differences regression compared health utility values (3-level version of EQ-5D; UK tariff) over 6 months for responders and nonresponders. Bootstrapped regression estimated the incremental quality-adjusted life-years (QALYs), probability of QALY gain after achieving the response criteria, and population monetary benefit of response. Results: Within the sample (n = 171), 18.2% achieved Major Clinical Response and 49.1% achieved Improvement at 6 months. Incremental health utility values were 0.0923 for Major Clinical Response and 0.0454 for Improvement. Expected incremental QALY gain at 6 months was 0.020 for Major Clinical Response and 0.012 for Improvement. Probability of QALY gain after achieving the response criteria was 77.6% for Major Clinical Response and 72.7% for Improvement. Population monetary benefit of response was £1 106 458 for Major Clinical Response and £649 134 for Improvement. Conclusions: Bespoke composite response endpoints are becoming more common to measure treatment response for multisystem diseases in trials and observational studies. Health technology assessment agencies face a growing challenge to establish whether these endpoints correspond with improved health gain. Health utility values can generate this evidence to enhance the usefulness of composite response endpoints for health technology assessment, decision making, and economic evaluation

CFD modeling of the building integrated with a novel design of a one-sided wind-catcher with water spray: Focus on thermal comfort

The rising energy demand for buildings has enhanced public awareness of sustainable energy sources and technologies. In particular, natural ventilation systems such as wind-catchers have attracted considerable new attention. A new wind-catcher design with single-stage direct-air evaporative cooling was proposed for indoor air conditioning. An Eulerian-Lagrangian approach employing the Realizable k-ε model was utilized to conduct the CFD simulations. Furthermore, the effects of inclining the bottom surface of the wind-catcher and installing a baffle across the flow path on the air temperature drop, water mass fraction, and air velocity distribution were studied. The inclined bottom surface led to more flow uniformity in the room compared to the conventional geometry. The baffled wind-catcher with β = 0, 30, 45, and 60° and unbaffled wind-catcher showed different flow patterns and thermal comforts. A methodology for evaluating the thermal comfort performance of evaporative cooling systems integrated into natural or passive cooling devices was also proposed based on the generated CFD results. The baffled wind-catcher with β = 60° combined with an evaporative cooling system significantly reduced the air temperature inside the building up to 17.4 °C and improved the occupants’ thermal comfort. The most suitable design for thermal comfort was also determined.</p

CFD modeling of the building integrated with a novel design of a one-sided wind-catcher with water spray: Focus on thermal comfort

The rising energy demand for buildings has enhanced public awareness of sustainable energy sources and technologies. In particular, natural ventilation systems such as wind-catchers have attracted considerable new attention. A new wind-catcher design with single-stage direct-air evaporative cooling was proposed for indoor air conditioning. An Eulerian-Lagrangian approach employing the Realizable k-ε model was utilized to conduct the CFD simulations. Furthermore, the effects of inclining the bottom surface of the wind-catcher and installing a baffle across the flow path on the air temperature drop, water mass fraction, and air velocity distribution were studied. The inclined bottom surface led to more flow uniformity in the room compared to the conventional geometry. The baffled wind-catcher with β = 0, 30, 45, and 60° and unbaffled wind-catcher showed different flow patterns and thermal comforts. A methodology for evaluating the thermal comfort performance of evaporative cooling systems integrated into natural or passive cooling devices was also proposed based on the generated CFD results. The baffled wind-catcher with β = 60° combined with an evaporative cooling system significantly reduced the air temperature inside the building up to 17.4 °C and improved the occupants’ thermal comfort. The most suitable design for thermal comfort was also determined.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Process and Energ