McMaster University

About: McMaster University is a education organization based out in Hamilton, Ontario, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 41361 authors who have published 101269 publications receiving 4251422 citations.

Evidence from rats that morphine tolerance is a learned response.

Abstract: It is proposed that the direct analgesic effect of morphine becomes attenuated over the course of successive administrations of the narcotic by a conditioned, compensatory, hyperalgesic response elicited by the administration procedure, the net result being analgesic tolerance. Using the "hot plate" analgesia assessment situation with rats, this conditioning view of tolerance is supported by several findings: (a) It is necessary to have reliable environmental cues predicting the systemic effects of morphine if tolerance is to be observed, (b) a hyperalgesic conditioned response may be observed in morphine-tolerant subjects when drug administration cues are followed by a placebo, and (c) merely by repeatedly presenting environmental cues previously associated with morphine (but now presented with a placebo), morphine tolerance can be extinguished.

Contribution of SHANK3 Mutations to Autism Spectrum Disorder

Abstract: Mutations in SHANK3, which encodes a synaptic scaffolding protein, have been described in subjects with an autism spectrum disorder (ASD). To assess the quantitative contribution of SHANK3 to the pathogenesis of autism, we determined the frequency of DNA sequence and copy-number variants in this gene in 400 ASD-affected subjects ascertained in Canada. One de novo mutation and two gene deletions were discovered, indicating a contribution of 0.75% in this cohort. One additional SHANK3 deletion was characterized in two ASD-affected siblings from another collection, which brings the total number of published mutations in unrelated ASD-affected families to seven. The combined data provide support that haploinsufficiency of SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing.

Evolution of Mechanical Ventilation in Response to Clinical Research

Abstract: Rationale: Recent literature in mechanical ventilation includes strong evidence from randomized trials. Little information is available regarding the influence of these trials on usual clinical practice.Objectives: To describe current mechanical ventilation practices and to assess the influence of interval randomized trials when compared with findings from a 1998 cohort.Methods: A prospective international observational cohort study, with a nested comparative study performed in 349 intensive care units in 23 countries. We enrolled 4,968 consecutive patients receiving mechanical ventilation over a 1-month period. We recorded demographics and daily data related to mechanical ventilation for the duration of ventilation. We systematically reviewed the literature and developed 11 practice-change hypotheses for the comparative cohort study before seeing these results. In assessing practice changes, we only compared data from the 107 intensive care units (1,675 patients) that also participated in the 1998 cohort...

Fundamental differences between SPH and grid methods

Abstract: We have carried out a comparison study of hydrodynamical codes by investigating their performance in modelling interacting multiphase fluids. The two commonly used techniques of grid and smoothed particle hydrodynamics (SPH) show striking differences in their ability to model processes that are fundamentally important across many areas of astrophysics. Whilst Eulerian grid based methods are able to resolve and treat important dynamical instabilities, such as Kelvin-Helmholtz or Rayleigh-Taylor, these processes are poorly or not at all resolved by existing SPH techniques. We show that the reason for this is that SPH, at least in its standard implementation, introduces spurious pressure forces on particles in regions where there are steep density gradients. This results in a boundary gap of the size of an SPH smoothing kernel radius over which interactions are severely damped.

A practical model of low‐volume high‐intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms

Abstract: High-intensity interval training (HIT) induces skeletal muscle metabolic and performance adaptations that resemble traditional endurance training despite a low total exercise volume. Most HIT studies have employed ‘all out’, variable-load exercise interventions (e.g. repeated Wingate tests) that may not be safe, practical and/or well tolerated by certain individuals. Our purpose was to determine the performance, metabolic and molecular adaptations to a more practical model of low-volume HIT. Seven men (21 ± 0.4 years, ml kg−1 min−1) performed six training sessions over 2 weeks. Each session consisted of 8–12 × 60 s intervals at ∼100% of peak power output elicited during a ramp peak test (355 ± 10 W) separated by 75 s of recovery. Training increased exercise capacity, as assessed by significant improvements on both 50 kJ and 750 kJ cycling time trials (P < 0.05 for both). Skeletal muscle (vastus lateralis) biopsy samples obtained before and after training revealed increased maximal activity of citrate synthase (CS) and cytochrome c oxidase (COX) as well as total protein content of CS, COX subunits II and IV, and the mitochondrial transcription factor A (Tfam) (P < 0.05 for all). Nuclear abundance of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) was ∼25% higher after training (P < 0.05), but total PGC-1α protein content remained unchanged. Total SIRT1 content, a proposed activator of PGC-1α and mitochondrial biogenesis, was increased by ∼56% following training (P < 0.05). Training also increased resting muscle glycogen and total GLUT4 protein content (both P < 0.05). This study demonstrates that a practical model of low volume HIT is a potent stimulus for increasing skeletal muscle mitochondrial capacity and improving exercise performance. The results also suggest that increases in SIRT1, nuclear PGC-1α, and Tfam may be involved in coordinating mitochondrial adaptations in response to HIT in human skeletal muscle.