New organometallic catalysts for process-friendly redox neutral alkylations

Borrowing hydrogen chemistry is a convenient method of carrying out alkylation reactions, by forming carbonyl compounds from alcohols in situ, creating more reactive intermediates. These aldehydes or ketones react and the resulting product is reduced by return of the hydrogen abstracted from the alcohol starting material. Previous work within the Marsden group led to the development of a new family of catalysts for N-alkylation borrowing hydrogen reactions, featuring a Cp* ligand functionalised with an amine tether. The possibility for expanding the scope of these catalysts to polyfunctionalised compounds was investigated, including protected and unprotected diamines and diols, and the synthesis of pharmaceutically relevant compounds. Optimisation studies were carried out to reach the highest turnover number for our catalyst, reaching a maximum turnover number of 2250 for our model reaction of the alkylation of piperidine with benzyl alcohol. After a brief investigation into the synthesis of new catalysts bearing modified tethers was unsuccessful, methodology was developed for the synthesis of our original catalyst under conditions more viable for scale-up. Experiments were carried out to determine the catalyst’s potential for carrying out C-alkylation reactions. In particular, carbonyl alkylations via an aldol pathway were successful, and were shown to be viable for a series of substituted acetophenones and benzyl alcohols, as well as various heteroaromatic compounds. A one-pot procedure for alkylation and subsequent reduction to the respective alcohol compound was developed and utilised to synthesise a series of compounds based on the taccabulin natural products, which were tested for anti-cancer activity. Finally, the possibility of these reactions being carried out to a lower yield in the absence of catalyst was investigated. The scope of these uncatalyzed reactions was determined to include only aromatic ketones, while our catalyst was shown to be able to carry out alkylations onto alkyl ketones with either aromatic or alkyl alcohols

“They are kids, they’re making bad choices, but they are not bad kids” : Motivations and deterrents for joyriding amongst Australian youth

Car theft and joyriding are becoming increasingly common in regional areas of Australia. Whilst the consequences of these actions can be fatal, surprisingly little is known about the motivations for young people who engage in these behaviours. This exploratory study draws from 17 in-depth interviews that were conducted as part of a pilot intervention program aimed at adolescents either already engaged or susceptible to car theft and joyriding behaviours. The findings suggest that joyriding predominately attracts disenfranchised youth who lack opportunities for education, employment, and leisure. For these adolescents, joyriding emerges to counterbalance disadvantage and alleviate the monotony in their lives. Interviewees also provide suggestions for deterring joyriding, such as providing young people with occupational opportunities that allow them to serve as role models to themselves and others and adrenaline-based activities to replace the thrills of joyriding

The Alt-Right Movement and National Security

Identifying the January 6 insurrection at the US Capitol as an inflection point, this article analyzes the historical relationship between White supremacy and the US military from Reconstruction after the Civil War to the present. The article posits causes for the disproportionate number of current and former members of the military associated with White power groups and proposes steps the Department of Defense can take to combat the problems posed by the association of the US military with these groups

The relative efficacy of cues for two-dimensional shape perception

AbstractThe visual system uses a variety of cues for form perception, including motion, color, binocular disparity, texture, and luminance. Physiological evidence suggests that these cues are processed by different neural mechanisms. Do the cues processed by some mechanisms convey any advantage for form perception when compared to cues processed by another? In response to this question we assessed the relative efficiency of several cues in conveying two-dimensional form from background noise. For the sake of comparison, every cue type used the same experimental design and stimulus set. Our results confirm that movement is one of the most efficient cues for shape perception. Also, a simple transient cue (an instantaneous flashing on or off) is equally useful. In comparison, local dot density (a type of texture cue) was the least efficient. The efficiencies of most other cues, such as color, stereopsis, and relative movement in noise, were conspicuously similar

A functional analysis of two transdiagnostic, emotion-focused interventions on nonsuicidal self-injury

OBJECTIVE: Nonsuicidal self-injury (NSSI) is prevalent and associated with clinically significant consequences. Developing time-efficient and cost-effective interventions for NSSI has proven difficult given that the critical components for NSSI treatment remain largely unknown. The aim of this study was to examine the specific effects of mindful emotion awareness training and cognitive reappraisal, 2 transdiagnostic treatment strategies that purportedly address the functional processes thought to maintain self-injurious behavior, on NSSI urges and acts. METHOD: Using a counterbalanced, combined series (multiple baseline and data-driven phase change) aggregated single-case experimental design, the unique and combined impact of these 2 4-week interventions was evaluated among 10 diagnostically heterogeneous self-injuring adults. Ecological momentary assessment was used to provide daily ratings of NSSI urges and acts during all study phases. RESULTS: Eight of 10 participants demonstrated clinically meaningful reductions in NSSI; 6 participants responded to 1 intervention alone, whereas 2 participants responded after the addition of the alternative intervention. Group analyses indicated statistically significant overall effects of study phase on NSSI, with fewer NSSI urges and acts occurring after the interventions were introduced. The interventions were also associated with moderate to large reductions in self-reported levels of anxiety and depression, and large improvements in mindful emotion awareness and cognitive reappraisal skills. CONCLUSIONS: Findings suggest that brief mindful emotion awareness and cognitive reappraisal interventions can lead to reductions in NSSI urges and acts. Transdiagnostic, emotion-focused therapeutic strategies delivered in time-limited formats may serve as practical yet powerful treatment approaches, especially for lower-risk self-injuring individuals.Dr. Barlow receives royalties from Oxford University Press, Guilford Publications Inc., Cengage Learning, and Pearson Publishing. Grant monies for various projects come from the National Institute of Mental Health (F31MH100761), the National Institute of Alcohol and Alcohol Abuse, and Colciencias (Government of Columbia Initiative for Science, Technology, and Health Innovation). Consulting and honoraria during the past several years have come from the Agency for Healthcare Research and Quality, the Foundation for Informed Medical Decision Making, the Department of Defense, the Renfrew Center, the Chinese University of Hong Kong, Universidad Catolica de Santa Maria (Arequipa, Peru), New Zealand Psychological Association, Hebrew University of Jerusalem, Mayo Clinic, and various American Universities. (F31MH100761 - National Institute of Mental Health; National Institute of Alcohol and Alcohol Abuse; Colciencias (Government of Columbia Initiative for Science, Technology, and Health Innovation))Accepted manuscrip

Experimental Manipulations to Test Theory-Driven Mechanisms of Cognitive Behavior Therapy

Despite decades of randomized-controlled trials demonstrating the efficacy of cognitive-behavior therapy (CBT), the mechanisms by which CBT achieves its effects remain unclear. Here, we describe how one adaptive intervention, the sequential multiple assignment randomized trial (SMART), can be used to randomize patients at multiple decision points in treatment to draw stronger causal claims about mechanisms unfolding in the course of CBT. We illustrate this design using preliminary data and case examples from an ongoing SMART in which we are testing the role of aversive reactions to negative emotions as a hypothesized mechanism of change in the Unified Protocol. Finally, we address common concerns with SMARTs and highlight how mechanistic research serves to personalize and optimize the delivery of CBT