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There is a bidirectional relationship between atrial fibrillation (AF) and chronic kidney disease (CKD), with multiple shared risk factors. This article discusses an integrated care approach toward the management of patients with AF, including those with CKD. There is an increasing risk of both ischemic stroke and bleeding with progressive deterioration of renal function, complicating the decision of optimal stroke prevention strategies among patients with AF and CKD. The optimal stroke prevention strategy in patients with AF and severe CKD remains uncertain. An individualized approach incorporating stroke and bleeding risk stratification is needed, especially in those with end-stage renal disease.

Background Cohort studies are among the most robust of observational studies but have issues with external validity. This study assesses threats to external validity (generalizability) in the European QUALity (EQUAL) study, a cohort study of people >65 years of age with Stage 4/5 chronic kidney disease. Methods Patients meeting the EQUAL inclusion criteria were identified in The Health Improvement Network database and stratified into those attending renal units, a secondary care cohort (SCC) and a not primary care cohort (PCC). Survival, progression to renal replacement therapy (RRT) and hospitalization were compared. Results The analysis included 250, 633 and 2464 patients in EQUAL, PCC and SCC. EQUAL had a higher proportion of men compared with PCC and SCC (60.0% versus 34.8% versus 51.4%). Increasing age ≥85 years {odds ratio [OR] 0.25 [95% confidence interval (CI) 0.15–0.40]} and comorbidity [Charlson Comorbidity Index ≥4, OR 0.69 (95% CI 0.52–0.91)] were associated with non-participation in EQUAL. EQUAL had a higher proportion of patients starting RRT at 1 year compared with SCC (8.1% versus 2.1%; P Conclusions This study provides evidence of how participants in a cohort study can differ from the broader population of patients, which is essential when considering external validity and application to local practice.

Background: Critically ill patients with COVID-19 infection on extracorporeal membrane oxygenation (ECMO) face high morbidity and mortality. Palliative care consultation may benefit these patients and their families. Prior to the pandemic, our institution implemented a policy of automatic palliative care consultation for all patients on ECMO due to the high mortality, medical complexity, and psychosocial distress associated with these cases. Objectives: The main objective was to describe the role of the palliative care team for patients on ECMO for COVID-19 infection. The secondary objective was to describe the clinical outcomes for this cohort. Design: Case series. Settings/Subjects: All patients age 18 or older infected by the novel coronavirus who required cannulation on ECMO from March through July of 2020, at an urban, academic medical center in the United States. Inter-disciplinary palliative care consultation occurred for all patients. Results: Twenty-three patients (median age 43 years [range 28-64], mean body mass index 34.9 kg/m2 [SD 9.2], 65% Hispanic ethnicity) were cannulated on ECMO. Eleven patients died during the hospitalization (48%). Patients older than 50 years of age demonstrated a trend toward increased odds of death compared to those younger than 50 years of age (OR 9.1, P = 0.07). Patients received an average of 6.8 (SD 3.7) palliative clinical encounters across all disciplines. The actions provided by the palliative care team included psychosocial support and counseling, determination of surrogate decision maker (for 100% of patients), pain management (83%), and non-pain symptom management (83%). Conclusions: Here, we present one of the first studies describing the patient characteristics, outcomes, and palliative care actions for critically ill patients with COVID-19 on ECMO. Almost half of the patients in this cohort died during their hospitalization. Given the high morbidity and mortality of this condition, we recommend involvement of palliative care for patients/families with COVID-19 infection who are on ECMO. The impact of palliative care on patient and family outcomes, such as symptom control, satisfaction with communication, rates of anxiety, and grief experience merits further investigation.

Since 2015, the Global Earthquake Model (GEM) Foundation and its partners have been supporting regional programs and bilateral collaborations to develop an open global earthquake risk model. These efforts led to the development of a repository of probabilistic seismic hazard models, a global exposure dataset comprising structural and occupancy information regarding the residential, commercial and industrial buildings, and a comprehensive set of fragility and vulnerability functions for the most common building classes. These components were used to estimate probabilistic earthquake risk globally using the OpenQuake-engine, an open-source software for seismic hazard and risk analysis. This model allows estimating a number of risk metrics such as annualized average losses or aggregated losses for particular return periods, which are fundamental to the development and implementation of earthquake risk mitigation measures.

Chemical modification of the gRNA and donor DNA has great potential for improving the gene editing efficiency of Cas9 and Cpf1, but has not been investigated extensively. In this report, we demonstrate that the gRNAs of Cas9 and Cpf1, and donor DNA can be chemically modified at their terminal positions without losing activity. Moreover, we show that 5’ fluorescently labeled donor DNA can be used as a marker to enrich HDR edited cells by a factor of two through cell sorting. In addition, we demonstrate that the gRNA and donor DNA can be directly conjugated together into one molecule, and show that this gRNA-donor DNA conjugate is three times better at transfecting cells and inducing HDR, with cationic polymers, than unconjugated gRNA and donor DNA. The tolerance of the gRNA and donor DNA to chemical modifications has the potential to enable new strategies for genome engineering. DOI: http://dx.doi.org/10.7554/eLife.25312.001, eLife digest There are several different technologies that can be used to make specific changes to particular genes in cells. These “gene editing” approaches have the potential to help humans in a variety of different ways, for example, to treat diseases that presently have no cure, or to improve the nutritional quality of crop plants. One such gene editing approach is known as CRISPR. To edit a specific gene, a molecule called a guide ribonucleic acid (or guide RNA for short) binds to a section of the gene and recruits an enzyme to cut the DNA encoding the gene in a particular location. Adding a “donor” DNA molecule that contains the desired “edit” can lead to the cell repairing the broken gene in a way that incorporates the desired change. Modifying the guide RNA or the donor DNA can enhance CRISPR editing. For example, extending the guide RNA molecules by adding “aptamer” sequences can enable researchers to specifically activate the genes that have been edited. It is also possible to add chemical tags to RNA and DNA, but it is not clear how chemical modifications to the guide RNA and donor DNA could affect CRISPR. Here Lee et al. investigated whether adding chemical tags to the guide RNA and/or donor DNA could enhance gene editing. The experiments show that the modified guide RNAs and donor DNAs were still active and could edit DNA in mouse and human cells. Adding a fluorescent molecule to the donor DNA allowed Lee et al. to track which cells contained donor DNA and separate them from other cells. The fluorescent cells had twice as much editing compared to groups of unsorted cells. In further experiments, the guide RNA and donor DNA were fused together and supplied to cells together with a DNA cutting enzyme. Cells containing this combined molecule had three times more editing than cells exposed to the original CRISPR system. This change may aid the development of new uses for CRISPR because it simplifies the system from three components (an enzyme, guide RNA and donor DNA) to just a cutting enzyme and the combined molecule. Overall, the findings of Lee et al. show that chemical modifications to guide RNA and donor DNA can make the CRISPR system more versatile. It opens up the possibility of new applications such as adding a targeting group that would direct the CRISPR Cas9 system to a specific cell type or tissue. DOI: http://dx.doi.org/10.7554/eLife.25312.002

Data are presented from the third combined vascular and peritoneal dialysis access audit. In 2014, 53 centres in England, Wales and Northern Ireland (out of 62) returned data on first access from 4,339 incident haemodialysis (HD) patients and 1,090 incident peritoneal dialysis (PD) patients. Of the 5,429 incident patients, 20.1% started dialysis on PD, 27.8% started with an arteriovenous fistula (AVF), 1.0% with an arteriovenous graft (AVG), 27.1% on a tunnelled line (TL) and 24.0% on a non-tunnelled line (NTL). Older patients (565 years) were more likely to start haemodialysis using AVF compared to their younger counterparts (36.2% vs. 32.8%). Thirteen of the nineteen centres (68%) using the physician led percutaneous insertion technique had over 20% of their incident patients starting on PD when compared to only seven out of fourteen centres (50%) which used single technique (open surgical or laparoscopic) for their PD catheter insertion. Wide variations were apparent between centres for use of AVF as the first haemodialysis access ranging from 10–54%. Eight of the 49 centres were achieving close to the 65% target for AV fistula in their incident patients. Length of time known to nephrology services and likelihood of commencing dialysis using either an AVF or a PD catheter are strongly associated. Patients who were known to a nephrologist for over one year were more likely to start dialysis with AVF, as compared to those who were referred between 90–365 days (39.2% vs. 24.6%). Similarly, patients who were known to a nephrologist between 90 days and one year were more likely to start on PD when compared to patients who were referred

Deterioration of reinforced concrete infrastructure such as bridges, tunnels, and buildings represents one of the major challenges currently facing developed countries. This deterioration leads to economic costs for maintenance and replacement, environmental impacts such increased global warming potential as a result of cement production and traffic emissions, and social costs related to traffic congestion and human health concerns. While engineering tools and methods for structural modelling and design of new reinforced concrete infrastructure are mature, the methods and tools for modelling decades-long deterioration and maintenance are much less developed. An approach for modelling structural deterioration of reinforced concrete components due to reinforcement corrosion is presented and a procedure is introduced to estimate the time-dependent structural response, described using time-dependent seismic fragility curves. The approach is part of a multi-disciplinary framework which includes physical, chemical, and electrochemical processes at the meso-scale coupled with mechanical deterioration processes, which are modelled using finite element methods, at the macroscale. While not detailed in this paper, when the time-dependent assessment of structures is integrated with life cycle assessment models that quantify the economic, environmental, and social impacts of infrastructure, the result is a comprehensive assessment methodology for the sustainability of deteriorating reinforced concrete infrastructure.