The asymmetric alkylation of enolates is a particularly versatile method for the construction of α-stereogenic carbonyl motifs, which are ubiquitous in synthetic chemistry. Over the past several ...decades, the focus has shifted to the development of new catalytic methods that depart from classical stoichiometric stereoinduction strategies (e.g., chiral auxiliaries, chiral alkali metal amide bases, chiral electrophiles, etc.). In this way, the enantioselective alkylation of prochiral enolates greatly improves the step- and redox-economy of this process, in addition to enhancing the scope and selectivity of these reactions. In this review, we summarize the origin and advancement of catalytic enantioselective enolate alkylation methods, with a directed emphasis on the union of prochiral nucleophiles with carbon-centered electrophiles for the construction of α-stereogenic carbonyl derivatives. Hence, the transformative developments for each distinct class of nucleophile (e.g., ketone enolates, ester enolates, amide enolates, etc.) are presented in a modular format to highlight the state-of-the-art methods and current limitations in each area.
This article examines some advantages and disadvantages of conducting online survey research. It explores current features, issues, pricing, and limitations associated with products and services, ...such as online questionnaire features and services to facilitate the online survey process, such as those offered by web survey businesses. The review shows that current online survey products and services can vary considerably in terms of available features, consumer costs, and limitations. It is concluded that online survey researchers should conduct a careful assessment of their research goals, research timeline, and financial situation before choosing a specific product or service.
Post-traumatic stress disorder (PTSD) affects 4% of women after birth yet there are very few questionnaire measures of postpartum PTSD that have been validated in this population. In addition, none ...of the available questionnaires assess postpartum PTSD in accordance with criteria specified in the latest edition of the Diagnostic and Statistical Manual DSM-5, (1). The City Birth Trauma Scale is a 29-item questionnaire developed to measure birth-related PTSD according to DSM-5 criteria of: stressor criteria (A), symptoms of re-experiencing (B), avoidance (C), negative cognitions and mood (D), and hyperarousal (E), as well as duration of symptoms (F), significant distress or impairment (E), and exclusion criteria or other causes (H). Two additional items from DSM-IV were also included on the basis of evidence suggesting they might be important in this population. The first was criterion A2 that women responded to events during birth with intense fear, helplessness or horror. The second was symptoms of emotional numbing. Items were first reviewed by researchers (
= 9) and postpartum women (
= 8) and revised accordingly. The questionnaire was then completed by 950 women recruited online. Results showed the City Birth Trauma Scale had excellent reliability (Cronbach's α = 0.92) and is easy to understand (Flesch reading score 64.17). Exploratory factor analysis found two factors which together accounted for 56% of the variance: (i) Birth-related symptoms (40.8% variance) and (ii) General symptoms (15.5% variance). PTSD symptoms were highly associated with distress, impaired functioning, and women reporting they wanted treatment (
= 0.50-0.61). Removing DSM-IV A2 criteria only increased births classified as traumatic by 2%. Adding the item on emotional numbing did not change the psychometric properties of the scale. These items were therefore removed. The City Birth Trauma Scale has good psychometric properties and the two symptom clusters identified are consistent with previous research on symptoms of postpartum PTSD. This scale therefore provides a promising measure of PTSD following childbirth that can be used in research and clinical practice. Future research should examine the scale's predictive validity using clinical interviews.
Flood hydrologic response is influenced by rainfall structure (i.e., variability in space and time). How this structure shapes flood frequency is unknown, and flood frequency analyses typically ...neglect or simplify potentially important aspects of rainfall variability. This study seeks to understand how rainfall structure impacts flood frequency. We use stochastic storm transposition combined with a 15‐year record of hourly, 4‐km2 radar rainfall to generate 10,000 synthetic extreme rain events. These events are resampled into four “scenarios” with differing spatial and temporal resolutions, which are used as input to a distributed hydrologic model. Analysis of variance is used to identify the proportions of total flood peak variability attributable to spatial and to temporal rainfall variability under two antecedent soil moisture conditions. We simulate peak discharges for recurrence intervals of 2 to 500 years for 1,343 subwatersheds ranging in size from 16 to 4,400 km2 in Turkey River in the Midwestern United States, which is situated in a typically humid continental climactic region. Antecedent soil moisture modulates the role of rainfall structure in simulated flood response, particularly for more frequent events and large watershed scales. Rainfall spatial structure is more important than temporal structure for drainage areas larger than approximately 2,000 km2 (approximately 200 km2) for wet (dry) initial soil conditions, especially when soils are dry, while the reverse is true for smaller subwatersheds. The results appear to be related to the differing propensities for surface and subsurface runoff production as a function of basin scale, event magnitude, and soil saturation. Our results suggest that hydrologic model‐based flood frequency analyses, and particularly efforts attempting to spanning a range of scales, must carefully consider rainfall structure.
Plain Language Summary
There is increasing interest in “derived flood frequency analysis”: the use of stochastically generated rainfall and high‐resolution distributed hydrologic models to understand current and future flood frequency. Potential issues surrounding rainfall structure, resolution, and accuracy in this context have received very little attention, however. Design storm methods, common in hydrologic engineering practice, use highly idealized assumptions regarding rainfall space‐time structure, and the consequences of these assumptions are poorly understood. This study seeks to better understand how flood frequency is affected by rainfall spatial and temporal structure, as well as how these effects are modulated by watershed initial conditions (i.e., antecedent soil moisture). The findings, which are summarized in the manuscript's , should be useful for future researchers and practitioners. We believe that this work constitutes a useful contribution in the effort to advance the derived flood frequency analysis.
Key Points
Framework for partitioning impacts of rainfall spatial and temporal variability on flood frequency
The impact of rainfall structure varies significantly with antecedent soil moisture, watershed scale, and event magnitude
Rainfall temporal variability is more important than spatial variability at small scales; the opposite is true at large scales
Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were ‘never the same’ prompted a scientific inquiry into the ...nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects.
Advanced applications of polymeric self-assembled structures require a stringent degree of control over such aspects as functionality location, morphology and size of the resulting assemblies. A loss ...of control in the polymeric building blocks of these assemblies can have drastic effects upon the final morphology or function of these structures. Gaining precise control over various aspects of the polymers, such as chain lengths and architecture, blocking efficiency and compositional distribution is a challenge and, hence, measuring the intrinsic mass and size dispersity within these areas is an important aspect of such control. It is of great importance that a good handle on how to improve control and accurately measure it is achieved. Additionally dispersity of the final structure can also play a large part in the suitability for a desired application. In this Tutorial Review, we aim to highlight the different aspects of dispersity that are often overlooked and the effect that a lack of control can have on both the polymer and the final assembled structure.
The clinical impact of the fibrate and thiazolidinedione drugs on dyslipidemia and diabetes is driven mainly through activation of two transcription factors, peroxisome proliferator-activated ...receptors (PPAR)-α and PPAR-γ. However, substantial differences exist in the therapeutic and side-effect profiles of specific drugs. This has been attributed primarily to the complexity of drug-target complexes that involve many coregulatory proteins in the context of specific target gene promoters. Recent data have revealed that some PPAR ligands interact with other non-PPAR targets. Here we review concepts used to develop new agents that preferentially modulate transcriptional complex assembly, target more than one PPAR receptor simultaneously, or act as partial agonists. We highlight newly described on-target mechanisms of PPAR regulation including phosphorylation and nongenomic regulation. We briefly describe the recently discovered non-PPAR protein targets of thiazolidinediones, mitoNEET, and mTOT. Finally, we summarize the contributions of on- and off-target actions to select therapeutic and side effects of PPAR ligands including insulin sensitivity, cardiovascular actions, inflammation, and carcinogenicity.
Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent.
We used serial questionnaire information from the Generations ...Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake.
Among 102,927 women recruited 2003-2013, with an average of 7.7 years of follow-up, 1815 developed invasive breast cancer. The HR (reference group was never smokers) was 1.14 (95% CI 1.03-1.25; P = 0.010) for ever smokers, 1.24 (95% CI 1.08-1.43; P = 0.002) for starting smoking at ages < 17 years, and 1.23 (1.07-1.41; P = 0.004) for starting smoking 1-4 years after menarche. Breast cancer risk was not statistically associated with interval from initiation of smoking to first birth (P-trend = 0.97). Women with a family history of breast cancer (ever smoker vs never smoker HR 1.35; 95% CI 1.12-1.62; P = 0.002) had a significantly larger HR in relation to ever smokers (P for interaction = 0.039) than women without (ever smoker vs never smoker HR 1.07; 95% CI 0.96-1.20; P = 0.22). The interaction was prominent for age at starting smoking (P = 0.003) and starting smoking relative to age at menarche (P = 0.0001).
Smoking was associated with a modest but significantly increased risk of breast cancer, particularly among women who started smoking at adolescent or peri-menarcheal ages. The relative risk of breast cancer associated with smoking was greater for women with a family history of the disease.
Effective transmission of sound from water to air is crucial for the enhancement of the detection sensitivity of underwater sound. However, only 0.1% of the acoustic energy is naturally transmitted ...at such a boundary. At audio frequencies, quarter-wave plates or multilayered antireflection coatings are too bulky for practical use for such enhancement. Here we present an acoustic metasurface of a thickness of only ∼λ/100, where λ is the wavelength in air, consisting of an array of meta-atoms that each contain a set of membranes and an air-filled cavity. We experimentally demonstrate that such a meta-atom increases the transmission of sound at ∼700 Hz by 2 orders of magnitude, allowing about 30% of the incident acoustic power from water to be transmitted into air. Applications include underwater sonic sensing and communication.
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Conventional rainfall frequency analysis faces several limitations. These include difficulty incorporating relevant atmospheric variables beyond precipitation and limited ability to depict the ...frequency of rainfall over large areas that is relevant for flooding. This study proposes a storm-based model of extreme precipitation frequency based on the atmospheric water balance equation. We developed a storm tracking and regional characterization (STARCH) method to identify precipitation systems in space and time from hourly ERA5 precipitation fields over the contiguous United States from 1951 to 2020. Extreme “storm catalogs” were created by selecting annual maximum storms with specific areas and durations over a chosen region. The annual maximum storm precipitation was then modeled via multivariate distributions of atmospheric water balance components using vine copula models. We applied this approach to estimate precipitation average recurrence intervals for storm areas from 5000 to 100 000 km2 and durations from 2 to 72 h in the Mississippi Basin and its five major subbasins. The estimated precipitation distributions show a good fit to the reference data from the original storm catalogs and are close to the estimates from conventional univariate GEV distributions. Our approach explicitly represents the contributions of water balance components in extreme precipitation. Of these, water vapor flux convergence is the main contributor, while precipitable water and a mass residual term can also be important, particularly for short durations and small storm footprints. We also found that ERA5 shows relatively good water balance closure for extreme storms, with a mass residual on average 10 % of precipitation. The approach can incorporate nonstationarities in water balance components and their dependence structures and can benefit from further advancements in reanalysis products and storm tracking techniques.
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