Atrial fibrillation and frailty: An observational cohort study using electronic healthcare records

Atrial fibrillation is common in older people, and is associated with increased mortality and stroke. Patients with atrial fibrillation/flutter (AF) also commonly have frailty, which is associated with increased risk of a range of further adverse clinical outcomes. However, there is a lack of evidence on the burden and management of AF in people with frailty. A study using the primary care electronic health records of 536,955 patients aged ≥65 years was conducted to investigate the burden of frailty and AF amongst older people, and their associations with clinical outcomes. A systematic review and meta-analysis was completed to establish the current knowledge base, and to inform the quantitative analyses. Baseline characteristics were described and compared between those with and without AF as well as by frailty category according to the electronic frailty index. Rates of all-cause mortality, stroke, bleeding (intracranial and gastrointestinal), transient ischaemic attack (TIA), and falls were calculated per 1000 person-years, and compared with the non-AF patient population. Cox proportional hazards modelling was used to determine unadjusted and adjusted risk for each clinical outcome and mortality, and presented as hazard ratios (HR) alongside 95% confidence intervals. The association between oral anticoagulation (OAC) prescription stratified by frailty category with clinical outcomes was investigated using Cox proportional hazards modelling. At baseline, 61,177 (11.4%) patients had AF. People with AF had a higher burden of frailty than those without (89.5% vs. 55.3%) and had higher rates of mortality, stroke, TIA and bleeding. Of patients with AF and eligible for OAC, it was prescribed in 53.1% (41.7% in robust, mild frailty 53.2%, moderate 55.6%, severe 53.4%). OAC was associated with a 19% reduction in all-cause mortality (HR 0.81, 95%CI 0.77-0.85) and 22% reduction in stroke (HR 0.78, 0.67-0.92). There was no statistically significant difference in rates of bleeding between those prescribed and not prescribed OAC. For the first time in a large representative cohort of older people, this study quantified the burden of AF and frailty, and their association with a range of clinical outcomes. This study found no evidence that OAC should be withheld on the basis of concomitant frailty

Relative limitations of increasing the number of modulation levels in computer generated holography

Phase and amplitude spatial light modulators (SLMs) capable of both binary and multi-level modulation are widely available and offer a wide range of technologies to choose from for holographic applications. While the replay fields generated with multi-level phase-only SLMs are of a significantly higher quality than those generated by equivalent binary phase-only SLMs, evidence is presented in this letter that this improvement is not as marked for amplitude SLMs, where multi-level devices offer only a small benefit over their binary counterparts. Heuristic and numerical justifications for this are discussed and conclusions drawn

An examination of recovery planning for forest-dwelling woodland caribou (Rangifer tarandus caribou) in Ontario, Canada

Ontario’s population of forest-dwelling woodland caribou is listed both federally and provincially as a species at risk. It is estimated that 20 000 woodland caribou remain in Ontario, of which approximately one quarter inhabit the boreal forest and are described as the sedentary forest-dwelling population. This paper examines the recovery strategy for this population developed by the Ministry of Natural Resources, as well as discussing the implications of provincial forestry policy on woodland caribou management. Commercial timber harvesting will likely soon be allowed in parts of the northern third of the province, in which woodland caribou habitat currently is relatively unimpaired by industrial development. Abstract in Norwegian / Sammendrag:Planlegging for bevaring av skogsøkotypen av Rangifer tarandus caribou i Ontario, CanadaSkogsvillreinen av skogsøkotypen i Ontario er vurdert som sårbar både føderalt og på provinsnivå. Av provinsens rundt 20 000 skogsvillrein hører omtrent en fjerdepart til den stasjonære skogsboende skogsøkoypen. Artikkelen ser på bevaringsstrategien som er utarbeidet av naturressursdepartementet i Ontario for denne spesielle bestanden og diskuterer konsekvensene for villreinen av provinsens skogpolitikk. Kommersiell hogst vil mest sannsynlig og snart bli tillatt i deler av Ontarios nordlige tredel der skogvillreinens leveområder er relativt upåvirket av industriell virksomhet

Hard to make space: improving access to privileged pharmacophores

Limited examples of the successful ring expansion of aziridines with sulfonium ylides to generate azetidines are known, but typically result in functional groups on azetidine that are not broadly useful for downstream chemistry. Described here is an investigation into the scope of this reaction including the discovery that N-activated 2-methoxy ester functionalised aziridines are not compatible with this protocol. Advances have also been made in understanding the reactivity of azirines with rhodium carbenoids to generate azetines from successful ring expansion, or N-vinylimine from ring opening. An alternative route to azetidines from the 1,3-cleavage of azabicyclo[1.1.0]butanes is described, along with a proposed route to highly functionalised azetidines with control over the absolute configuration at each step. Early success reacting a range of reagents with an azabicyclo[1.1.0]butane of moderate steric bulk has been shown, as well as early steps towards a novel azetidine 3-sulfonamide synthesis. Difluorocyclopropanation of alkenes using fluorinated acetate salts is often a slow, inefficient and energy-intensive process. Reported here is a modified protocol enabling the preparation of 1,1-difluorocyclopropanes in less than five minutes, using microwave irradiation. The new procedure is considerably faster than previously reported methods, employs easily removed, low-boiling point solvents and avoids the use of highly toxic or ozone-depleting substances. The method has been exemplified in a high-yielding synthesis of a difluoro analogue of a clinically used drug substance, and has also shown some utility in preparing 1,1-difluorocyclopropenes and as a novel procedure for the synthesis of halogenated alkyl ether esters from cyclic ethers. Other investigations into the generation and reactivity of difluorocarbene reported here include successful proof of concept experiments showing the sensitivity of allyl functionalised difluoromethylene containing compounds to palladium species to generate difluorocarbene, as well as exploratory reactions to build on methods to generate 2,2-difluoroaziridines by addition of difluorocarbene to imines

Evidence against memorial facilitation and context-dependent memory effects through the chewing of gum

The experiment examined the prediction that chewing gum at learning and/or recall facilitated subsequent word recall. Chewing gum at learning significantly impaired recall, indicating that the chewing of gum has a detrimental impact upon initial word encoding. In addition, a context-dependent memory effect was reported for those participants who both learned and recalled in the absence of gum, however a context dependent effect was not found with chewing gum. The findings contradict previous research

A cross-sectional study of predatory publishing emails received by career development grant awardees

OBJECTIVE: To investigate the scope of academic spam emails (ASEs) among career development grant awardees and the factors associated with the amount of time spent addressing them. DESIGN: A cross-sectional survey of career development grant investigators via an anonymous online survey was conducted. In addition to demographic and professional information, we asked investigators to report the number of ASEs received each day, how they determined whether these emails were spam and time they spent per day addressing them. We used bivariate analysis to assess factors associated with the amount of time spent on ASEs. SETTING: An online survey sent via email on three separate occasions between November and December 2016. PARTICIPANTS: All National Institutes of Health career development awardees funded in the 2015 fiscal year. MAIN OUTCOME MEASURES: Factors associated with the amount of time spent addressing ASEs. RESULTS: A total of 3492 surveys were emailed, of which 206 (5.9%) were returned as undeliverable and 96 (2.7%) reported an out-of-office message; our overall response rate was 22.3% (n=733). All respondents reported receiving ASEs, with the majority (54.4%) receiving between 1 and 10 per day and spending between 1 and 10 min each day evaluating them. The amount of time respondents reported spending on ASEs was associated with the number of peer-reviewed journal articles authored (p<0.001), a history of publishing in open access format (p<0.01), the total number of ASEs received (p<0.001) and a feeling of having missed opportunities due to ignoring these emails (p=0.04). CONCLUSIONS: ASEs are a common distraction for career development grantees that may impact faculty productivity. There is an urgent need to mitigate this growing problem

An Introduction to the Calibration of Computer Models

In the context of computer models, calibration is the process of estimating unknown simulator parameters from observational data. Calibration is variously referred to as model fitting, parameter estimation/inference, an inverse problem, and model tuning. The need for calibration occurs in most areas of science and engineering, and has been used to estimate hard to measure parameters in climate, cardiology, drug therapy response, hydrology, and many other disciplines. Although the statistical method used for calibration can vary substantially, the underlying approach is essentially the same and can be considered abstractly. In this survey, we review the decisions that need to be taken when calibrating a model, and discuss a range of computational methods that can be used to compute Bayesian posterior distributions