Quantitative Structure–Selectivity Relationships in Enantioselective Catalysis: Past, Present, and Future

The dawn of the 21st century has brought with it a surge of research related to computer-guided approaches to catalyst design. In the past two decades, chemoinformatics, the application of informatics to solve problems in chemistry, has increasingly influenced prediction of activity and mechanistic investigations of organic reactions. The advent of advanced statistical and machine learning methods, as well as dramatic increases in computational speed and memory, has contributed to this emerging field of study. This review summarizes strategies to employ quantitative structure−selectivity relationships (QSSR) in asymmetric catalytic reactions. The coverage is structured by initially introducing the basic features of these methods. Subsequent topics are discussed according to increasing complexity of molecular representations. As the most applied subfield of QSSR in enantioselective catalysis, the application of local parametrization approaches and linear free energy relationships (LFERs) along with multivariate modeling techniques is described first. This section is followed by a description of global parametrization methods, the first of which is continuous chirality measures (CCM) because it is a single parameter derived from the global structure of a molecule. Chirality codes, global, multivariate descriptors, are then introduced followed by molecular interaction fields (MIFs), a global descriptor class that typically has the highest dimensionality. To highlight the current reach of QSSR in enantioselective transformations, a comprehensive collection of examples is presented. When combined with traditional experimental approaches, chemoinformatics holds great promise to predict new catalyst structures, rationalize mechanistic behavior, and profoundly change the way chemists discover and optimize reactions

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Explaining variation in Down's syndrome screening uptake: comparing the Netherlands with England and Denmark using documentary analysis and expert stakeholder interviews.

Background: The offer of prenatal Down’s syndrome screening is part of routine antenatal care in most of Europe; however screening uptake varies significantly across countries. Although a decision to accept or reject screening is a personal choice, it is unlikely that the widely differing uptake rates across countries can be explained by variation in individual values alone. The aim of this study was to compare Down’s syndrome screening policies and programmes in the Netherlands, where uptake is relatively low ( 90% respectively), in an attempt to explain the observed variation in national uptake rates. Methods: We used a mixed methods approach with an embedded design: a) documentary analysis and b) expert stakeholder analysis. National central statistical offices and legal documents were studied first to gain insight in demographic characteristics, cultural background, organization and structure of healthcare followed by documentary analysis of primary and secondary sources on relevant documents on DSS policies and programme. To enhance interpretation of these findings we performed in-depth interviews with relevant expert stakeholders. Results: There were many similarities in the demographics, healthcare systems, government abortion legislation and Down’s syndrome screening policy across the studied countries. However, the additional cost for Down’s syndrome screening over and above standard antenatal care in the Netherlands and an emphasis on the ‘right not to know’ about screening in this country were identified as potential explanations for the ‘low’ uptake rates of Down’s syndrome screening in the Netherlands. The social context and positive framing of the offer at the service delivery level may play a role in the relatively high uptake rates in Denmark. Conclusions: This paper makes an important contribution to understanding how macro-level demographic, social and healthcare delivery factors may have an impact on national uptake rates for Down’s syndrome screening. It has suggested a number of policy level and system characteristics that may go some way to explaining the relatively low uptake rates of Down’s syndrome screening in the Netherlands when compared to England and Denmark

Asymmetric Catalysis with Chiral Lewis Bases: A New Frontier in Main Group Chemistry

The concept of the electron pair bond formulated by G. N. Lewis provides the foundation for our understanding of chemical structure and reactivity. The consequences of the donor–acceptor interactions between bases and acids are manifest in the spectacular diversity of transformations that form the basis for chemical synthesis. By systematic analysis of the origins of these phenomena, it is possible to gain a unified picture of how electron pair donors (Lewis bases) can modulate and influence chemical reactions by enhancing either (or both) electrophilic or (and) nucleophilic character. This article provides a brief overview of the conceptual basis and theoretical foundation for these phenomena and illustrates a number of reactions primarily in Group 14 that are susceptible to catalysis by Lewis bases