Review of Established and Emergent Methods for the Production of C4 Olefins

Current production of C4 olefins is dominated by naphtha cracking and butane dehydrogenation, but significant research interest is developing in alternate feedstocks due to an abundance of inexpensive natural gas and bioethanol. The current C4 olefin production methods are costly, make use of already-depleted petroleum resources, and are often hazardous to workers, which forms the impetus for investigation into alternative methods and assessment of their viability as a future means of olefin production. Methods of natural gas conversion to higher order hydrocarbons are discussed, including Fischer-Tropsch synthesis and oxidative methane coupling, each of which could form the first step in a hypothetical natural gas-to-olefins process. The historically common Lebedev, Ostromislensky, and Fripiat methods for 1,3-butadiene production from ethanol feedstocks are described and analyzed, although these processes largely fell out of favor in the decades following World War II in favor of sources derived from naphtha cracking. Another well-known process involving C4 olefins, olefin metathesis, is considered, although the reaction is more commonly used to produce propylene. Biological processes are discussed as well, including the well-known production of bioethanol from sugars and starches, and also more novel processes such as an effort to use genetically engineered microorganisms to produce specific intermediates for olefin production, and in some cases, direct olefin production from these organisms. Finally, several promising schemes are identified and analyzed, in an attempt to compare their potential viability in key areas. Two of the most promising emergent methods today identified in this review are the bio-catalyzed production of 1,4-butanediol and/or butadiene using E. coli, and a microwave radiation-assisted scheme in which methane is selectively dimerized twice to form 1-butene

Recent developments in the PySCF program package

PySCF is a Python-based general-purpose electronic structure platform that supports first-principles simulations of molecules and solids as well as accelerates the development of new methodology and complex computational workflows. This paper explains the design and philosophy behind PySCF that enables it to meet these twin objectives. With several case studies, we show how users can easily implement their own methods using PySCF as a development environment. We then summarize the capabilities of PySCF for molecular and solid-state simulations. Finally, we describe the growing ecosystem of projects that use PySCF across the domains of quantum chemistry, materials science, machine learning, and quantum information science. Published under license by AIP Publishing.Peer reviewe

Surveillance of Vermont wildlife in 2021–2022 reveals no detected SARS-CoV-2 viral RNA

Abstract Previous studies have documented natural infections of SARS-CoV-2 in various domestic and wild animals. More recently, studies have been published noting the susceptibility of members of the Cervidae family, and infections in both wild and captive cervid populations. In this study, we investigated the presence of SARS-CoV-2 in mammalian wildlife within the state of Vermont. 739 nasal or throat samples were collected from wildlife throughout the state during the 2021 and 2022 harvest season. Data was collected from red and gray foxes (Vulpes vulples and Urocyon cineroargentus, respectively), fishers (Martes pennati), river otters (Lutra canadensis), coyotes (Canis lantrans), bobcats (Lynx rufus rufus), black bears (Ursus americanus), and white-tailed deer (Odocoileus virginianus). Samples were tested for the presence of SARS-CoV-2 via quantitative RT-qPCR using the CDC N1/N2 primer set and/or the WHO-E gene primer set. Surprisingly, we initially detected a number of N1 and/or N2 positive samples with high cycle threshold values, though after conducting environmental swabbing of the laboratory and verifying with a second independent primer set (WHO-E) and PCR without reverse transcriptase, we showed that these were false positives due to plasmid contamination from a construct expressing the N gene in the general laboratory environment. Our final results indicate that no sampled wildlife were positive for SARS-CoV-2 RNA, and highlight the importance of physically separate locations for the processing of samples for surveillance and experiments that require the use of plasmid DNA containing the target RNA sequence. These negative findings are surprising, given that most published North America studies have found SARS-CoV-2 within their deer populations. The absence of SARS-CoV-2 RNA in populations sampled here may provide insights in to the various environmental and anthropogenic factors that reduce spillover and spread in North American’s wildlife populations

Weight-bearing in ankle fractures: An audit of UK practice.

INTRODUCTION: The purpose of this national study was to audit the weight-bearing practice of orthopaedic services in the National Health Service (NHS) in the treatment of operatively and non-operatively treated ankle fractures. METHODS: A multicentre prospective two-week audit of all adult ankle fractures was conducted between July 3rd 2017 and July 17th 2017. Fractures were classified using the AO/OTA classification. Fractures fixed with syndesmosis screws or unstable fractures (>1 malleolus fractured or talar shift present) treated conservatively were excluded. No outcome data were collected. In line with NICE (The National Institute for Health and Care Excellence) criteria, "early" weight-bearing was defined as unrestricted weight-bearing on the affected leg within 3 weeks of injury or surgery and "delayed" weight-bearing as unrestricted weight-bearing permitted after 3 weeks. RESULTS: 251 collaborators from 81 NHS hospitals collected data: 531 patients were managed non-operatively and 276 operatively. The mean age was 52.6 years and 50.5 respectively. 81% of non-operatively managed patients were instructed for early weight-bearing as recommended by NICE. In contrast, only 21% of operatively managed patients were instructed for early weight-bearing. DISCUSSION: The majority of patients with uni-malleolar ankle fractures which are managed non-operatively are treated in accordance with NICE guidance. There is notable variability amongst and within NHS hospitals in the weight-bearing instructions given to patients with operatively managed ankle fractures. CONCLUSION: This study demonstrates community equipoise and suggests that the randomized study to determine the most effective strategy for postoperative weight-bearing in ankle fractures described in the NICE research recommendation is feasible

The beam and detector of the NA62 experiment at CERN

NA62 is a fixed-target experiment at the CERN SPS dedicated to measurements of rare kaon decays. Such measurements, like the branching fraction of the K(+) → π(+) ν bar nu decay, have the potential to bring significant insights into new physics processes when comparison is made with precise theoretical predictions. For this purpose, innovative techniques have been developed, in particular, in the domain of low-mass tracking devices. Detector construction spanned several years from 2009 to 2014. The collaboration started detector commissioning in 2014 and will collect data until the end of 2018. The beam line and detector components are described together with their early performance obtained from 2014 and 2015 data.NA62 is a fixed-target experiment at the CERN SPS dedicated to measurements of rare kaon decays. Such measurements, like the branching fraction of the $K^{+} \rightarrow \pi^{+} \nu \bar\nu$ decay, have the potential to bring significant insights into new physics processes when comparison is made with precise theoretical predictions. For this purpose, innovative techniques have been developed, in particular, in the domain of low-mass tracking devices. Detector construction spanned several years from 2009 to 2014. The collaboration started detector commissioning in 2014 and will collect data until the end of 2018. The beam line and detector components are described together with their early performance obtained from 2014 and 2015 data

A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo