Effects of parent-child affective quality during high school years on subsequent substance use

The literature indicates that the quality of affective relationships between youth and parents is associated with lower levels of a range of problem behaviors during childhood, early and late adolescence. While the protective effect of parental monitoring on substance use in the high school and post high school years has been demonstrated, there is a knowledge gap concerning effects of parent-child affective quality (PCAQ) during the same periods. We tested a conceptual theoretical model to examine the effects of PCAQ on substance use following high school. The sample was from a RCT that assessed adolescents in rural Iowa from the seventh grade through two years after high school (N=456). We specified direct effects of PCAQ in 12th grade on drunkenness, smoking and illicit drug use during the two years immediately following high school graduation. We also specified the effects of early substance use initiation (alcohol, tobacco and marijuana use reported at baseline) on later use. The direct effect of PCAQ in 12th grade on substance use was significant for all substances during at least one of the two years past graduation (ypg). Results were: drunkenness 1 ypg, β=-.126, p<.05; smoking 1 ypg, β=-.119, p<.05; 2 ypg, β=-.146, p<.05; illicit drug use 2 ypg, β=-.165, p<.05. Some significant indirect effects of PCAQ at baseline, via PCAQ at 12th grade, were found. Results also indicated significant direct effects of early initiation on two of the three substances, albeit with a different pattern of effects over time for each substance by years post high school. Importantly, while early initiation remains the strongest predictor of long-term tobacco and illicit drug use, results show how PCAQ might reduce its harmful effects.peer-reviewe

New Urbanism: From Exception to Norm—The Evolution of a Global Movement

This thematic issue explores the evolution of the New Urbanism, a normative planning and urban design movement that has contributed to development throughout the world. Against a dominant narrative that frames the movement as a straightforward application of principles that has yielded many versions of the same idea, this issue instead proposes an examination of New Urbanism as heterogeneous in practice, shaped through multiple contingent factors that spell variegated translations of core principles. The contributing authors investigate how variegated forms of New Urbanism emerge, interrogate why place-based contingencies lead to differentiation in practice, and explain why the movement continues to be represented as a universal phenomenon despite such on-the-ground complexities. Together, the articles in this thematic issue offer a powerful rebuttal to the idea that our understanding of the New Urbanism is somehow complete and provide original ideas and frameworks with which to reassess the movement’s complexity and understand its ongoing impact

Beach Vegetation and Oceanic Processes Study of Popham State Park Beach, Reid State Park Beach, and Small Pt. Beach

Beach Vegetation and Oceanic Processes Study of Popham State Park Beach, Reid State Park Beach, and Small Pt. Beach by Philip Trudeau, Paul J. Godfrey and Barry S. Timson Prepared Under Cooperative Agreement Between the Maine Department of Conservation and the Soil Conservation Service, United States Department of Agriculture, September 1977. On Cover: Time and Tide Resource Conservation and Development Project. Contents: List of Figures / List of Tables / Introduction / Plant Community Research / Oceanic Processes / Historic Analysis of Barrier Beach Movement and Erosion / Dune Dynamics / Suggestions for Long Term Management / Appendices A - E / Literature Citedhttps://digitalcommons.usm.maine.edu/me_collection/1088/thumbnail.jp

Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function

<p>Abstract</p> <p>Background</p> <p>Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc).</p> <p>Results</p> <p>DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D₂autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D₂autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D₂receptor antagonist, sulpiride (5 μM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D₂autoreceptors. In addition, initial blockade of D₂autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13).</p> <p>Conclusion</p> <p>Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D₂autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.</p

Technology supported collaborative learning.

"This research is supported by le ministère de l'Éducation, du Loisir et du Sport dans le cadre du Programme d'aide à la recherche sur l'enseignement et l'apprentissage (PAREA)"Titre de la couv.: Technology supported collaborative learning.Titre de l'écran-titre (visionné le 10 sept. 2009).Également disponible en format papier.Bibliogr

Estimating tibial stress throughout the duration of a treadmill run

This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this record.Introduction: Stress fractures of the tibia are a problematic injury amongst runners of all levels. Quantifying tibial stress using a modelling approach provides an alternative to invasive assessments that may be used to detect changes in tibial stress during running. This study aimed to assess the repeatability of a tibial stress model and to use this model to quantify changes in tibial stress that occur throughout the course of a 40-minute prolonged treadmill run. Methods: Synchronised force and kinematic data were collected during prolonged treadmill running from fourteen recreational male rearfoot runners on two separate occasions. During each session, participants ran at their preferred speed for two consecutive 20-minute runs, separated by a 2-minute pause. The tibia was modelled as a hollow ellipse and bending moments and stresses at the distal 1/3 of the tibia were estimated using beam theory combined with inverse dynamics and musculoskeletal modelling. Results: Intraclass correlation coefficients indicated good-to-excellent repeatability for peak stress values between sessions. Peak anterior and posterior stresses increased following 20 minutes of prolonged treadmill running and were 15% and 12% greater respectively after 40 minutes of running compared with the start of the run. Conclusion: The hollow elliptical tibial model presented is a repeatable tool that can be utilised to assess within-participant changes in peak tibial stress during running. The increased stresses observed during a prolonged treadmill run may have implications for the development of tibial stress fracture.Brooks Running Company, Seattle, WA, USA

hERG potassium channel gating is mediated by N- and C-terminal region interactions

Human ether-á-go-go–related gene (hERG) potassium channels have voltage-dependent closing (deactivation) kinetics that are unusually slow. A Per-Arnt-Sim (PAS) domain in the cytoplasmic N-terminal region of hERG regulates slow deactivation by making a direct interaction with another part of the hERG channel. The mechanism for slow deactivation is unclear, however, because the other regions of the channel that participate in regulation of deactivation are not known. To identify other functional determinants of slow deactivation, we generated hERG channels with deletions of the cytoplasmic C-terminal regions. We report that hERG channels with deletions of the cyclic nucleotide–binding domain (CNBD) had accelerated deactivation kinetics that were similar to those seen in hERG channels lacking the PAS domain. Channels with dual deletions of the PAS domain and the CNBD did not show further acceleration in deactivation, indicating that the PAS domain and the CNBD regulate deactivation by a convergent mechanism. A recombinant PAS domain that we previously showed could directly regulate PAS domain–deleted channels did not regulate channels with dual deletions of the PAS domain and CNBD, suggesting that the PAS domain did not interact with CNBD-deleted channels. Biochemical protein interaction assays showed that glutathione S-transferase (GST)–PAS (but not GST) bound to a CNBD-containing fusion protein. Coexpression of PAS domain–deleted subunits (with intact C-terminal regions) and CNBD-deleted subunits (with intact N-terminal regions) resulted in channels with partially restored slow deactivation kinetics, suggesting regulatory intersubunit interactions between PAS domains and CNBDs. Together, these data suggest that the mechanism for regulation of slow deactivation in hERG channels is an interaction between the N-terminal PAS domain and the C-terminal CNBD

Elevated Mitochondrial Bioenergetics and Axonal Arborization Size Are Key Contributors to the Vulnerability of Dopamine Neurons

SummaryAlthough the mechanisms underlying the loss of neurons in Parkinson’s disease are not well understood, impaired mitochondrial function and pathological protein aggregation are suspected as playing a major role. Why DA (dopamine) neurons and a select small subset of brain nuclei are particularly vulnerable to such ubiquitous cellular dysfunctions is presently one of the key unanswered questions in Parkinson’s disease research. One intriguing hypothesis is that their heightened vulnerability is a consequence of their elevated bioenergetic requirements. Here, we show for the first time that vulnerable nigral DA neurons differ from less vulnerable DA neurons such as those of the VTA (ventral tegmental area) by having a higher basal rate of mitochondrial OXPHOS (oxidative phosphorylation), a smaller reserve capacity, a higher density of axonal mitochondria, an elevated level of basal oxidative stress, and a considerably more complex axonal arborization. Furthermore, we demonstrate that reducing axonal arborization by acting on axon guidance pathways with Semaphorin 7A reduces in parallel the basal rate of mitochondrial OXPHOS and the vulnerability of nigral DA neurons to the neurotoxic agents MPP+ (1-methyl-4-phenylpyridinium) and rotenone. Blocking L-type calcium channels with isradipine was protective against MPP+ but not rotenone. Our data provide the most direct demonstration to date in favor of the hypothesis that the heightened vulnerability of nigral DA neurons in Parkinson’s disease is directly due to their particular bioenergetic and morphological characteristics

Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.

BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of$61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and$110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients &lt;60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug