Herein, we describe a study into the scope and origin of an enantiodivergent effect in the palladium-catalyzed decarboxylative asymmetric protonation. By switching the achiral proton source, both enantiomers of a series of tertiary α-aryl-1-indanones are readily accessed from the corresponding α-aryl-β-keto allyl esters. In this example of dual stereocontrol, enantioselectivities up to 94% (S) and 92% (R) were achieved using Meldrum's acid and formic acid, respectively. In an attempt to rationalize this switch in absolute configuration an investigation of the ambiguous mechanism of the decarboxylative asymmetric protonation was conducted. A novel catalytic cycle for the reaction with formic acid is proposed and subjected to a variety of experimental studies.
The pathways model of problem gambling suggests the existence of three developmental pathways to problem gambling, each differentiated by a set of predisposing biopsychosocial characteristics: behaviorally conditioned (BC), emotionally vulnerable (EV), and biologically vulnerable (BV) gamblers. This study examined the empirical validity of the Pathways Model among adolescents followed up to early adulthood. A prospective-longitudinal design was used, thus overcoming limitations of past studies that used concurrent or retrospective designs. Two samples were used: (1) a population sample of French-speaking adolescents (N = 1033) living in low socio-economic status (SES) neighborhoods from the Greater Region of Montreal (Quebec, Canada), and (2) a population sample of adolescents (N = 3017), representative of French-speaking students in Quebec. Only participants with at-risk or problem gambling by mid-adolescence or early adulthood were included in the main analysis (n = 180). Latent Profile Analyses were conducted to identify the optimal number of profiles, in accordance with participants' scores on a set of variables prescribed by the Pathways Model and measured during early adolescence: depression, anxiety, impulsivity, hyperactivity, antisocial/aggressive behavior, and drug problems. A four-profile model fit the data best. Three profiles differed from each other in ways consistent with the Pathways Model (i.e., BC, EV, and BV gamblers). A fourth profile emerged, resembling a combination of EV and BV gamblers. Four profiles of at-risk and problem gamblers were identified. Three of these profiles closely resemble those suggested by the Pathways Model.
The aim of this study was to assess Irish and Canadian obstetricians in training ("trainees") experience, confidence, and comfort in performing operative vaginal delivery (OVD). Trainees in Obstetrics and Gynaecology in the University of Toronto and the Royal College of Physicians of Ireland (RCPI) were invited to participate in an anonymous online survey reviewing experience as primary operator of OVD. Trainee confidence and comfort was self-assessed based upon their last few OVDs. The response rate was 55% amongst Canadian trainees (31/56) and 44% amongst Irish trainees (21/48). When comparing Irish with Canadian trainee experience, the median numbers of vacuum and forceps deliveries performed by Irish trainees as primary operator were reported to be higher [125 (range 10-150) vs 20 (range 5-40); p < 0.0001 (ventouse), 45 (range 10-150) vs 6 (range 1-12); p = 0.0001 (forceps)]. Despite this, trainee confidence between the groups did not differ [confidence score: 18.7 (SD 3.2) vs 17.8 (SD 3.5), p = 0.3]. There were some differences regarding comfort in certain aspects of OVD, most notably increased comfort in Irish trainees in pre-procedure assessment skills of OVD. With falling OVD rates worldwide, training experience is declining. Despite higher numbers of OVD within the Irish trainee group, there was no difference in trainee confidence between the two groups. These results suggest that a high number of cases as primary operator may not be required to establish operator confidence in performing a procedure. Irish trainees self-reported more comfort in non-technical skills of OVD, suggesting a step-wise effect of experience on first technical and then non-technical skills.
In this Perspective, we describe current challenges and recent advances in efficient delivery and targeting of nanoparticles in vivo. We discuss cancer therapy, nanoparticle-biomolecule interactions, nanoparticle trafficking in cells, and triggers and responses to nanoparticle-cell interactions. No matter which functionalization strategy to target cancer is chosen, passive or active targeting, more than 99% of the nanoparticles administered in vivo end up in the mononuclear phagocytic system, mainly sequestered by macrophages. Comprehensive studies, such as the one reported by MacParland et al. in this issue of ACS Nano, will help to close the gap between nanotechnology-based drug-delivery solutions and advanced medicinal products.
The synthesis of potent inhibitors of GH93 arabinanases as well as a synthesis of a chromogenic substrate to measure GH93 arabinanase activity are described. An insight into the reasons behind the potency of the inhibitors was gained through X-ray crystallographic analysis of the arabinanase Arb93A from Fusarium graminearum. These compounds lay a foundation for future inhibitor development as well as for the use of the chromogenic substrate in biochemical studies of GH93 arabinanases.
The concept of efficient electrolysis by linking photoelectrochemical biphasic H2 evolution and water oxidation processes in the cathodic and anodic compartments of an H-cell, respectively, is introduced. Overpotentials at the cathode and anode are minimised by incorporating light-driven elements into both biphasic reactions. The concepts viability is demonstrated by electrochemical H2 production from water splitting utilising a polarised water-organic interface in the cathodic compartment of a prototype H-cell. At the cathode the reduction of decamethylferrocenium cations ([Cp2*Fe((III))](+)) to neutral decamethylferrocene (Cp2*Fe((II))) in 1,2-dichloroethane (DCE) solvent takes place at the solid electrode/oil interface. This electron transfer process induces the ion transfer of a proton across the immiscible water/oil interface to maintain electroneutrality in the oil phase. The oil-solubilised proton immediately reacts with Cp2*Fe((II)) to form the corresponding hydride species, [Cp2*Fe((IV))(H)](+). Subsequently, [Cp2*Fe((IV))(H)](+) spontaneously undergoes a chemical reaction in the oil phase to evolve hydrogen gas (H2) and regenerate [Cp2*Fe((III))](+), whereupon this catalytic Electrochemical, Chemical, Chemical (ECC') cycle is repeated. During biphasic electrolysis, the stability and recyclability of the [Cp2*Fe((III))](+)/Cp2*Fe((II)) redox couple were confirmed by chronoamperometric measurements and, furthermore, the steady-state concentration of [Cp2*Fe((III))](+) monitored in situ by UV/vis spectroscopy. Post-biphasic electrolysis, the presence of H2 in the headspace of the cathodic compartment was established by sampling with gas chromatography. The rate of the biphasic hydrogen evolution reaction (HER) was enhanced by redox electrocatalysis in the presence of floating catalytic molybdenum carbide (Mo2C) microparticles at the immiscible water/oil interface. The use of a superhydrophobic organic electrolyte salt was critical to ensure proton transfer from water to oil, and not anion transfer from oil to water, in order to maintain electroneutrality after electron transfer. The design, testing and successful optimisation of the operation of the biphasic electrolysis cell under dark conditions with Cp2*Fe((II)) lays the foundation for the achievement of photo-induced biphasic water electrolysis at low overpotentials using another metallocene, decamethylrutheneocene (Cp2*Ru((II))). Critically, Cp2*Ru((II)) may be recycled at a potential more positive than that of proton reduction in DCE.
The salutary effects of resistance exercise training (RET) are well established, including increased strength and function; however, less is known regarding the effects of RET on mental health outcomes. Aerobic exercise has well-documented positive effects on anxiety, but a quantitative synthesis of RET effects on anxiety is needed. To estimate the population effect size for resistance exercise training (RET) effects on anxiety and to determine whether variables of logical, theoretical, and/or prior empirical relation to anxiety moderate the overall effect. Thirty-one effects were derived from 16 articles published before February 2017, located using Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science. Trials involved 922 participants (mean age = 43 ± 21 years, 68% female/32% male) and included both randomization to RET (n = 486) or a non-active control condition (n = 436), and a validated anxiety outcome measured at baseline, mid-, and/or post-intervention. Hedges' d effect sizes were computed and random effects models were used for all analyses. Meta-regression quantified the extent to which participant and trial characteristics moderated the mean effect. RET significantly reduced anxiety symptoms (Δ = 0.31, 95% CI 0.17-0.44; z = 4.43; p < 0.001). Significant heterogeneity was not indicated (Q T(30) = 40.5, p > 0.09; I (2) = 28.3%, 95% CI 10.17-42.81); sampling error accounted for 77.7% of observed variance. Larger effects were found among healthy participants (Δ = 0.50, 95% CI 0.22-0.78) compared to participants with a physical or mental illness (Δ = 0.19, 95% CI 0.06-0.31, z = 2.16, p < 0.04). Effect sizes did not significantly vary according to sex (β = -0.31), age (β = -0.10), control condition (β = 0.08), program length (β = 0.07), session duration (β = 0.08), frequency (β = -0.10), intensity (β = -0.18), anxiety recall time frame (β = 0.21), or whether strength significantly improved (β = 0.19) (all p ≥ 0.06). RET significantly improves anxiety symptoms among both healthy participants and participants with a physical or mental illness. Improvements were not moderated by sex, or based on features of RET. Future trials should compare RET to other empirically-supported therapies for anxiety.
Dynamic sitting approaches have been advocated to increase seated energy expenditure with the view of lessening the sedentary nature of the task. This study compared energy expenditure (EE) and overall body discomfort on a novel dynamic chair with a standard office chair. Fifteen pain-free participants completed a DVD viewing task on both chairs in a randomised order. Energy expenditure and discomfort were collected simultaneously. Linear mixed models were used to analyse steady-state EE recorded on each of the chairs. Differences in discomfort were analysed using Wilkoxon Signed Rank Tests. Sitting on the novel dynamic chair significantly (p = 0.005) increased energy expenditure compared to a standard office chair. The discomfort experienced was mild overall, but was significantly greater on the dynamic chair (p = 0.004). Whilst the EE was seen to be significantly higher on the dynamic chair, the MET values are still below 1.5 METS. Thus, the use of a dynamic chair does not seem to be the most effective measure to prevent sedentary behaviour. Practitioner Summary: Sitting on a dynamic chair increased energy expenditure compared to sitting on a standard office chair among pain-free participants. Whilst the EE was seen to be significantly higher on the dynamic chair, the MET values are still below 1.5 METS (low level EE).