An induced-fit model for asymmetric organocatalytic reactions: a case study of the activation of olefins via chiral Brønsted acid catalysts

We elucidate the stereo-controlling factors of the asymmetric intramolecular hydroalkoxylation of terminal olefins catalyzed by bulky Brønsted acids [Science 2018, 359 (6383), 1501–1505] using high-level electronic structure methods. The catalyst–substrate interaction is described using a dispersion-driven induced-fit model, in which the conformational changes of the catalyst and of the substrate in the transition states are governed to a large extent by London dispersion forces. The distortion energy of the catalyst is dominated by the change in the intramolecular dispersion interactions, while intermolecular catalyst–substrate dispersion interactions are the major stabilizing contribution in the transition state. This model provides a new general framework in which to discuss the stereoselectivity of transformations catalyzed by such confined organocatalysts

Methods for the thematic synthesis of qualitative research in systematic reviews

<p>Abstract</p> <p>Background</p> <p>There is a growing recognition of the value of synthesising qualitative research in the evidence base in order to facilitate effective and appropriate health care. In response to this, methods for undertaking these syntheses are currently being developed. Thematic analysis is a method that is often used to analyse data in primary qualitative research. This paper reports on the use of this type of analysis in systematic reviews to bring together and integrate the findings of multiple qualitative studies.</p> <p>Methods</p> <p>We describe thematic synthesis, outline several steps for its conduct and illustrate the process and outcome of this approach using a completed review of health promotion research. Thematic synthesis has three stages: the coding of text 'line-by-line'; the development of 'descriptive themes'; and the generation of 'analytical themes'. While the development of descriptive themes remains 'close' to the primary studies, the analytical themes represent a stage of interpretation whereby the reviewers 'go beyond' the primary studies and generate new interpretive constructs, explanations or hypotheses. The use of computer software can facilitate this method of synthesis; detailed guidance is given on how this can be achieved.</p> <p>Results</p> <p>We used thematic synthesis to combine the studies of children's views and identified key themes to explore in the intervention studies. Most interventions were based in school and often combined learning about health benefits with 'hands-on' experience. The studies of children's views suggested that fruit and vegetables should be treated in different ways, and that messages should not focus on health warnings. Interventions that were in line with these suggestions tended to be more effective. Thematic synthesis enabled us to stay 'close' to the results of the primary studies, synthesising them in a transparent way, and facilitating the explicit production of new concepts and hypotheses.</p> <p>Conclusion</p> <p>We compare thematic synthesis to other methods for the synthesis of qualitative research, discussing issues of context and rigour. Thematic synthesis is presented as a tried and tested method that preserves an explicit and transparent link between conclusions and the text of primary studies; as such it preserves principles that have traditionally been important to systematic reviewing.</p

The impact of resolution on the representation of Greenland barrier winds and katabatic flows

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 42 (2015): 3011–3018, doi:10.1002/2015GL063550.Southern Greenland is characterized by a number of low-level high wind speed weather systems that are the result of topographic flow distortion. These systems include barrier winds and katabatic flow that occur along its southeast coast. Global atmospheric reanalyses have proven to be important tools in furthering our understanding of these orographic winds and their role in the climate system. However, there is evidence that the mesoscale characteristics of these systems may be missed in these global products. Here we show that the Arctic System Reanalysis, a higher-resolution regional reanalysis, is able to capture mesoscale features of barrier winds and katabatic flow that are missed or underrepresented in ERA-I, a leading modern global reanalysis. This suggests that our understanding of the impact of these wind systems on the coupled-climate system can be enhanced through the use of higher-resolution regional reanalyses or model data.2015-10-1

Harnessing the ambiphilicity of silyl nitronates in a catalytic asymmetric approach to aliphatic β³-amino acids

Nitronate anions, formally generated by α-deprotonating the corresponding nitroalkanes, are highly nucleophilic and versatile intermediates in many carbon–carbon bond-forming reactions. In contrast, the corresponding silyl nitronates are ambiphilic and react, at the same carbon atom, with both electrophiles and nucleophiles. However, while their nucleophilicity has been well exploited in catalytic enantioselective reactions with imines and aldehydes, utilizing the electrophilicity of silyl nitronates in asymmetric synthesis has remained elusive. Here we report the facile, efficient and general reactivity of readily available silyl nitronates with silyl ketene acetals, catalysed by highly Lewis-acidic and confined silylium imidodiphosphorimidate catalysts. The products of this reaction, so-called nitroso acetals, are obtained in excellent enantioselectivity and can be easily converted into N-Boc-β3-amino acid esters in a single step

Brain and spinal stimulation therapies for phantom limb pain: a systematic review.

BACKGROUND: Although many treatments exist for phantom limb pain (PLP), the evidence supporting them is limited and there are no guidelines for PLP management. Brain and spinal cord neurostimulation therapies are targeted at patients with chronic PLP but have yet to be systematically reviewed. OBJECTIVE: To determine which types of brain and spinal stimulation therapy appear to be the best for treating chronic PLP. DESIGN: Systematic reviews of effectiveness and epidemiology studies, and a survey of NHS practice. POPULATION: All patients with PLP. INTERVENTIONS: Invasive interventions - deep brain stimulation (DBS), motor cortex stimulation (MCS), spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation. Non-invasive interventions - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). MAIN OUTCOME MEASURES: Phantom limb pain and quality of life. DATA SOURCES: Twelve databases (including MEDLINE and EMBASE) and clinical trial registries were searched in May 2017, with no date limits applied. REVIEW METHODS: Two reviewers screened titles and abstracts and full texts. Data extraction and quality assessments were undertaken by one reviewer and checked by another. A questionnaire was distributed to clinicians via established e-mail lists of two relevant clinical societies. All results were presented narratively with accompanying tables. RESULTS: Seven randomised controlled trials (RCTs), 30 non-comparative group studies, 18 case reports and 21 epidemiology studies were included. Results from a good-quality RCT suggested short-term benefits of rTMS in reducing PLP, but not in reducing anxiety or depression. Small randomised trials of tDCS suggested the possibility of modest, short-term reductions in PLP. No RCTs of invasive therapies were identified. Results from small, non-comparative group studies suggested that, although many patients benefited from short-term pain reduction, far fewer maintained their benefits. Most studies had important methodological or reporting limitations and few studies reported quality-of-life data. The evidence on prognostic factors for the development of chronic PLP from the longitudinal studies also had important limitations. The results from these studies suggested that pre-amputation pain and early PLP intensity are good predictors of chronic PLP. Results from the cross-sectional studies suggested that the proportion of patients with severe chronic PLP is between around 30% and 40% of the chronic PLP population, and that around one-quarter of chronic PLP patients find their PLP to be either moderately or severely limiting or bothersome. There were 37 responses to the questionnaire distributed to clinicians. SCS and DRG stimulation are frequently used in the NHS but the prevalence of use of DBS and MCS was low. Most responders considered SCS and DRG stimulation to be at least sometimes effective. Neurosurgeons had mixed views on DBS, but most considered MCS to rarely be effective. Most clinicians thought that a randomised trial design could be successfully used to study neurostimulation therapies. LIMITATION: There was a lack of robust research studies. CONCLUSIONS: Currently available studies of the efficacy, effectiveness and safety of neurostimulation treatments do not provide robust, reliable results. Therefore, it is uncertain which treatments are best for chronic PLP. FUTURE WORK: Randomised crossover trials, randomised N-of-1 trials and prospective registry trials are viable study designs for future research. STUDY REGISTRATION: The study is registered as PROSPERO CRD42017065387. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Wetland succession in a permafrost collapse: interactions between fire and thermokarst

To determine the influence of fire and thermokarst in a boreal landscape, we investigated peat cores within and adjacent to a permafrost collapse feature on the Tanana River Floodplain of Interior Alaska. Radioisotope dating, diatom assemblages, plant macrofossils, charcoal fragments, and carbon and nitrogen content of the peat profile indicate ~600 years of vegetation succession with a transition from a terrestrial forest to a sedge-dominated wetland over 100 years ago, and to a &lt;i&gt;Sphagnum&lt;/i&gt;-dominated peatland in approximately 1970. The shift from sedge to &lt;i&gt;Sphagnum&lt;/i&gt;, and a decrease in the detrended tree-ring width index of black spruce trees adjacent to the collapse coincided with an increase in the growing season temperature record from Fairbanks. This concurrent wetland succession and reduced growth of black spruce trees indicates a step-wise ecosystem-level response to a change in regional climate. In 2001, fire was observed coincident with permafrost collapse and resulted in lateral expansion of the peatland. These observations and the peat profile suggest that future warming and/or increased fire disturbance could promote permafrost degradation, peatland expansion, and increase carbon storage across this landscape; however, the development of drought conditions could reduce the success of both black spruce and &lt;i&gt;Sphagnum&lt;/i&gt;, and potentially decrease the long-term ecosystem carbon storage

Signalling and pharmacological properties of the P2Y14 receptor: The P2Y14 receptor

The P2Y14 receptor is a relatively broadly expressed G protein-coupled receptor that is prominently associated with immune and inflammatory cells as well as with many epithelia. This receptor historically was thought to be activated selectively by UDP-glucose and other UDP-sugars. However, UDP is also a very potent agonist of this receptor, and may prove to be one of its most important cognate activators

Supplemental Nutrition Assistance Program (SNAP)-authorized retailers received a low score using the Business Impact Assessment for Obesity and population-level nutrition (BIA-Obesity) tool

Background: The Supplemental Nutrition Assistance Program (SNAP) supports Americans with lower income to purchase dietary products at authorized retailers. This research aimed to evaluate SNAP-authorized retailers’ public commitments in support of nutrition security and to examine differences between traditional grocers and nontraditional (e.g., convenience, drug, dollar) SNAP-authorized retailers’ public commitments. Methods: Prominent United States (U.S.) SNAP-authorized retailers nationally and in two U.S. states (California and Virginia) were identified based on number of store locations (n = 61). Public information available in grey literature were reviewed and scored using the Business Impact Assessment for Obesity and population-level nutrition (BIA-Obesity) tool. SNAP-authorized retailers were classified as traditional (e.g., grocery) or nontraditional (e.g., non-grocery) retailers. Total BIA-Obesity from 0 to 615, representing low to optimal support) and category scores were calculated for corporate strategy, relationships with external organizations, product formulation, nutrition labeling, product and brand promotion, and product accessibility. Descriptive statistics were used to describe BIA-Obesity scores overall and by category. Mann–Whitney U was used to test for potential differences in median BIA-Obesity total scores between traditional and nontraditional SNAP-authorized retailers (a priori, p \u3c 0.05). Results: Average total BIA-Obesity scores for SNAP-authorized retailers ranged from 0 to 112 (16.5 ± 23.3). Total BIA-Obesity scores for traditional SNAP-authorized retailers (32.7 ± 33.6; median 25) were higher than nontraditional SNAP-authorized retailer scores (11.2 ± 16; median 5) (p = 0.008). For BIA-Obesity categories, average scores were highest for the category relationships with external organizations (8.3 ± 10.3) and lowest for promotion practices (0.6 ± 2.1). Conclusions: Results of this research underscore a dearth of available evidence and substantial opportunity for improvement regarding SNAP-authorized retailer strategies to support nutrition security among Americans with lower income