Effective Prevention of Adolescent Substance Abuse – Educational versus Deterrent Approaches

Substance abuse, especially among adolescents, has long been an important issue in society. In light of the adverse impact of substance abuse, scholars, educators, and policy-makers have proposed different approaches to prevent and reduce such abuse. This paper investigates the effectiveness of the two prominent approaches—educational and deterrent—in preventing and reducing adolescent substance abuse. The educational approach (e.g., school-based prevention programming) tends to be more comprehensive and better grounded in theories than the deterrent approach (e.g., drug testing). The educational approach not only targets multiple psychosocial factors contributing to substance abuse, but it is also supported by empirical studies showing that school-based prevention programming is effective in preventing substance abuse and has long-lasting positive influences on adolescent development. Practical implications of implementing school-based prevention programming are also discussed. L'abus d'alcool ou d'autres drogues, surtout chez les adolescents, constitue depuis longtemps une préoccupation importante de la société. À la lumière de l'impact défavorable de cet abus, les chercheurs, enseignants et décideurs ont proposé différentes approches pour le prévenir et le limiter. Cet article porte sur l'efficacité de deux approches importantes, l'une pédagogique, l'autre dissuasive, visant la prévention et la réduction de l'abus d'alcool ou d'autres drogues chez les adolescents. L'approche pédagogique (par ex. les programmes de prévention en milieu scolaire) est, de façon générale, plus globale et mieux fondée sur les théories que l'approche dissuasive (par ex. dépistage des drogues). Non seulement l'approche pédagogique cible-t-elle les divers facteurs psychosociaux qui contribuent à cet abus, elle est de plus appuyée par des études empiriques indiquant que les programmes de prévention en milieu scolaire sont des outils efficaces dans la prévention de l'abus d'alcool ou d'autres drogues et qu'ils ont un impact positif à long terme sur le développement des adolescents. Nous discutons des répercussions pratiques de la mise en œuvre des programmes de prévention en milieu scolaire

orvara::An Efficient Code to Fit Orbits using Radial Velocity, Absolute, and/or Relative Astrometry

We present an open-source Python package, Orbits from Radial Velocity, Absolute, and/or Relative Astrometry (orvara), to fit Keplerian orbits to any combination of radial velocity, relative astrometry, and absolute astrometry data from the Hipparcos-Gaia Catalog of Accelerations. By combining these three data types, one can measure precise masses and sometimes orbital parameters even when the observations cover a small fraction of an orbit. orvara achieves its computational performance with an eccentric anomaly solver five to ten times faster than commonly used approaches, low-level memory management to avoid python overheads, and by analytically marginalizing out parallax, barycenter proper motion, and the instrument-specific radial velocity zero points. Through its integration with the Hipparcos and Gaia intermediate astrometry package htof, orvara can properly account for the epoch astrometry measurements of Hipparcos and the measurement times and scan angles of individual Gaia epochs. We configure orvara with modifiable .ini configuration files tailored to any specific stellar or planetary system. We demonstrate orvara with a case study application to a recently discovered white dwarf/main sequence (WD/MS) system, HD 159062. By adding absolute astrometry to literature RV and relative astrometry data, our comprehensive MCMC analysis improves the precision of HD 159062B's mass by more than an order of magnitude to $0.6083^{+0.0083}_{-0.0073}\,M_\odot$. We also derive a low eccentricity and large semimajor axis, establishing HD 159062AB as a system that did not experience Roche lobe overflow.Comment: 24 pages, 5 figures, 5 tables. AJ accepted with minor changes. orvara is available at https://github.com/t-brandt/orvar

Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice

INTRODUCTION: Obesity is a major risk factor for the development of osteoarthritis in both weight-bearing and nonweight-bearing joints. The mechanisms by which obesity influences the structural or symptomatic features of osteoarthritis are not well understood, but may include systemic inflammation associated with increased adiposity. In this study, we examined biomechanical, neurobehavioral, inflammatory, and osteoarthritic changes in C57BL/6J mice fed a high-fat diet. METHODS: Female C57BL/6J mice were fed either a 10% kcal fat or a 45% kcal fat diet from 9 to 54 weeks of age. Longitudinal changes in musculoskeletal function and inflammation were compared with endpoint neurobehavioral and osteoarthritic disease states. Bivariate and multivariate analyses were conducted to determine independent associations with diet, percentage body fat, and knee osteoarthritis severity. We also examined healthy porcine cartilage explants treated with physiologic doses of leptin, alone or in combination with IL-1α and palmitic and oleic fatty acids, to determine the effects of leptin on cartilage extracellular matrix homeostasis. RESULTS: High susceptibility to dietary obesity was associated with increased osteoarthritic changes in the knee and impaired musculoskeletal force generation and motor function compared with controls. A high-fat diet also induced symptomatic characteristics of osteoarthritis, including hyperalgesia and anxiety-like behaviors. Controlling for the effects of diet and percentage body fat with a multivariate model revealed a significant association between knee osteoarthritis severity and serum levels of leptin, adiponectin, and IL-1α. Physiologic doses of leptin, in the presence or absence of IL-1α and fatty acids, did not substantially alter extracellular matrix homeostasis in healthy cartilage explants. CONCLUSIONS: These results indicate that diet-induced obesity increases the risk of symptomatic features of osteoarthritis through changes in musculoskeletal function and pain-related behaviors. Furthermore, the independent association of systemic adipokine levels with knee osteoarthritis severity supports a role for adipose-associated inflammation in the molecular pathogenesis of obesity-induced osteoarthritis. Physiologic levels of leptin do not alter extracellular matrix homeostasis in healthy cartilage, suggesting that leptin may be a secondary mediator of osteoarthritis pathogenesis

Host-linked soil viral ecology along a permafrost thaw gradient

Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are poorly understood1,2,3,4,5,6,7. The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans8,9,10, remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling

Affinity enrichment of extracellular vesicles from plasma reveals mRNA changes associated with acute ischemic stroke

Currently there is no in vitro diagnostic test for acute ischemic stroke (AIS), yet rapid diagnosis is crucial for effective thrombolytic treatment. We previously demonstrated the utility of CD8(+) T-cells’ mRNA expression for AIS detection; however extracellular vesicles (EVs) were not evaluated as a source of mRNA for AIS testing. We now report a microfluidic device for the rapid and efficient affinity-enrichment of CD8(+) EVs and subsequent EV’s mRNA analysis using droplet digital PCR (ddPCR). The microfluidic device contains a dense array of micropillars modified with anti-CD8α monoclonal antibodies that enriched 158 ± 10 nm sized EVs at 4.3 ± 2.1 × 109 particles/100 µL of plasma. Analysis of mRNA from CD8(+) EVs and their parental T-cells revealed correlation in the expression for AIS-specific genes in both cell lines and healthy donors. In a blinded study, 80% test positivity for AIS patients and controls was revealed with a total analysis time of 3.7 h

Automated multi-level governance compliance checking

An institution typically comprises constitutive rules, which give shape and meaning to social interactions and regulative rules, which prescribe agent behaviour in the society. Regulative rules guide social interaction, in particular when they are coupled with reward and punishment regulations that are enforced for (non-)compliance. Institution examples include legislation and contracts. Formal institutional reasoning frameworks automate ascribing social meaning to agent interaction and determining whether those actions have social meanings that comprise (non-)compliant behaviour. Yet, institutions do not just govern societies. Rather, in what is called multi-level governance, institutional designs at lower governance levels (e.g., national legislation at the national level) are governed by higher level institutions (e.g., directives, human rights charters and supranational agreements). When an institution design is found to be non-compliant, punishments can be issued by annulling the legislation or imposing fines on the responsible designers (i.e., government). In order to enforce multi-level governance, higher governance levels (e.g., courts applying human rights) must check lower level institution designs (e.g., national legislation) for compliance; in order to avoid punishment, lower governance levels (e.g., national governments) must check their institution designs are compliant with higher-level institutions before enactment. However, checking non-compliance of institution designs in multi-level governance is non-trivial. In particular, because institutions in multi-level governance operate at different levels of abstraction. Lower level institutions govern with concrete regulations whilst higher level institutions typically comprise increasingly vague and abstract regulations. To address this issue, in this paper we propose a formal framework with a novel semantics that defines compliance between concrete lower level institutions and abstract higher level institutions. The formal framework is complemented by a sound and complete computational framework that automates compliance checking, which we apply to a real-world case study

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer