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High titers of cold agglutinins jeopardize the quality of an apheresis product meant for autologous or allogeneic transplant. Management of transplant patients with cold agglutinin disease (CAD) is often experience-based and under reported, yet decisions must be made quickly to optimize product management and patient outcomes. There remains a lack of data quantifying cell recovery and viability when using various warming methodologies.To expand the published experimental data on this subject, our human cellular therapy lab compared cellular recoveries and viabilities after manipulation of cryopreserved apheresis products through various warming methodologies: (1) extended warming in a water bath, (2) warming via blood warmer and infusion pump, and (3) warming in a water bath followed by infusion pump as a control to assess potential shear stress effects.The presented studies demonstrate that all methods of product warming produce the same rates of recovery of total and viable cells across vital cell types prior to patient administration. Statistically, use of an extended water bath protocol provided a marginal benefit in recovery of total nucleated cells, though this effect is diminished when products are held for an extended period to simulate a delay in administration.These results can inform decisions to improve patient care and minimize product manipulation and loss. Centers are encouraged to use this information to guide proactive measures to establish a standard operating procedure to manage CAD cases.

This paper outlines the evaluation strategy of the EMPOWERCARE, an EU Interreg 2 Seas funded social innovation project, which involves a partnership of local authorities, universities and non-governmental organisations from four European countries: Belgium, France, the Netherlands and the United Kingdom. Partners are working in collaboration with local people aged 65+, and those aged 50+ with at least one chronic condition, to respond to current gaps in the care of older people. The project aims specifically to contribute to person-centred care and technology knowledge transfer whilst reducing isolation, loneliness and increasing solidarity amongst older people and their communities. During the project, partners are jointly developing a strategy for implementing good-practice models, a workforce transformation approach via shared training and a technology blueprint with emphasis on caring digital technologies to address the rising demand for health and social care services for older people. The project addresses this challenge by drawing on community assets, involving older people in decisions about their own health and wellbeing, enabling them to keep healthier and in their own homes and communities safely for longer. The project’s evaluation aims to measure the impact of the EMPOWERCARE initiative across 7 pilot sites in the 4 participating countries. Given the Covid-19 pandemic, the evaluation design has been developed with a view to being agile and able to respond to complex and shifting situations, and especially so in terms of what and how data are collected. A realist synthesis approach (Pawson & Tilley, 2004) guides the evaluation within a descriptive case study design (Yin 2003) to identify and contextualise the project strategies that are influential within and across the 7 different case study sites. The evaluation uses multiple interdisciplinary methods, such as surveys, Photovoice and Social Return on Investment, to capture a range of perspectives across three timepoints, baseline (T0), mid-point (T1) and end-point (T2). Online surveys are conducted with both end-users and the workforce in all pilot sites at T0 and T2. At T1, end-users are actively involved in creating visual data through Photovoice to capture their lived experiences with local initiatives in pilot sites. Visual data are going to be displayed at pilot site exhibitions targeted to key local stakeholders and members of the workforce. Focus groups will be conducted with all participants reflecting on the visual data exhibition to explore insights about the initiative from current and future perspectives. This aspect is informed by a Social Return on Investment approach. The sequential data collection of multiple sources and longitudinal study design identify patterns of change and impact. The evaluation design will deliver a theory-driven rich explanation of what works about EMPOWERCARE and for whom, why, how and in what circumstances it works. The analysis of the evaluation findings will contribute to a more empowered person-centred approach, with more inclusive and caring digital health solutions that will allow policy makers to develop localised, efficient and social-value driven services to meet the rising needs of older people in the European regions.

Remote consultations have become more frequent since the COVID-19 pandemic, and a range of recommendations on conducting these consultations is available Here the authors summarise key points for clinicians to bear in mind

Infant language development includes a complex social dynamic between adults and infants. Infant vocalization is a well-studied area of development, however adult perception of infant vocalization is less well-understood. The effectiveness of identifications made by adults may impact the social feedback loops that drive development. We collected data from a final sample of 460 undergraduate students who listened to brief (100-500 ms) audio clips of infant vocalization. Participants were asked to identify infants in the audio clips as male/female, English/non-English, and their approximate age. Participants were unable to determine the sex of the infant better than chance but showed better than chance performance for language and age, albeit with low accuracy. Exploratory follow-up analyses did not reveal an effect of caregiving experience, childcare experience, or participant gender on a participants’ ability to correctly identify the infant’s age, sex, or language. These findings suggest that adult caregivers, regardless of experience, are able to perceive elements of infant vocalizations that may influence responsiveness to infant vocal development. However, performance is far from perfect.

Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Objectives To present our experience with the Patterson-Forester extra-anatomic stent (EAS, Cook Medical) in patients with benign ureteric obstruction. Utilising an EAS in complex ureteric obstruction can have a significant positive impact on quality of life as a result of removing external drainage devices. Materials and methods Between November 2012 and January 2021 10 patients underwent 33 EAS procedures. All patients had benign ureteric obstruction. Mean age at primary procedure was 58 years (range 43-63). Median follow-up was 27.5 months (range 11-100). Results Eight patients were successfully managed with EAS, with 6 patients continuing to have routine EAS exchanges. Two patients had the distal end exteriorised due to refractory bladder symptoms. There were three short-term failures; the distal end migrated out of the bladder requiring reinsertion one week later; one patient developed urosepsis requiring intravenous antibiotics and the stent removing within 30 days; one proximal stent migrated resulting in cutaneous erosion. The patient is now awaiting further EAS insertion. Conclusion The Patterson-Forester EAS is another tool in the endourologists' armamentarium when managing complex ureteric obstruction. In appropriately selected patients, it can improve their quality of life and is a durable long-term strategy in benign obstruction.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant., Graphical Abstract, Highlights • Increasing frequency of SARS-CoV-2 D614G is consistent with a selective advantage • Phylodynamic analyses do not show significantly different growth of D614G clusters • There is no association of D614G replacement with greater severity of infection • The D614G replacement is associated with higher viral loads and younger patient age, Analysis of the spread and frequency of SARS-CoV-2 D614G in the United Kingdom suggests a selective advantage for this strain that is associated with higher viral loads in younger patients but not higher COVID-19 clinical severity or mortality.

As atmospheric carbon dioxide concentrations, [CO2Air], continue their uncontrolled rise, the capacity of soils to accumulate or retain carbon is uncertain. Free-air CO2 enrichment (FACE) experiments have been conducted to better understand the plant, soil and ecosystem response to elevated [CO2], frequently employing commercial CO2 that imparts a distinct isotopic signal to the system for tracing carbon. We conducted a FACE experiment in 1998 and 1999, whereby sorghum (C4 photosynthetic pathway) was grown in four replicates of four treatments using a split-strip plot design: (i) ambient CO2/ample water (365 μmol mol−1, “Control–Wet”), (ii) ambient CO2/water stress (“Control–Dry”), (iii) CO2-enriched (560 μmol mol−1, “FACE–Wet”), and (iv) CO2-enriched/water stressed (“FACE–Dry”). The stable-carbon isotope composition of the added CO2 (in FACE treatments) was close to that of free atmosphere background values, so the subsequent similar 13C-enriched carbon signal photosynthetically fixed by C4 sorghum plants could be used to trace the fate of carbon in both FACE and control treatments. Measurement of soil organic carbon content (SOC (%) = gC/gdry soil × 100%) and δ13C at three depths (0–15, 15–30, and 30–60 cm) were made on soils from the beginning and end of the two experimental growing seasons. A progressive ca. 0.5‰–1.0‰ δ13C increase in the upper soil SOC in all treatments over the course of the experiment indicated common entry of new sorghum carbon into the SOC pools. The 0–15 cm SOC in FACE treatments was 13C-enriched relative to the Control by ca. 1‰, and according to isotopic mass balance, the fraction of the new sorghum-derived SOC in the Control–Wet treatment at the end of the second season was 8.4%, 14.2% in FACE–Wet, 6.5% in Control–Dry, and 14.2% in FACE–Dry. The net SOC enhancement resulting from CO2 enrichment was therefore 5.8% (or 2.9% y−1 of experiment) under ample water and 7.7% (3.8% y−1 of experiment) under limited water, which matches the pattern of greater aboveground biomass increase with elevated [CO2Air] under the Dry treatment, but no parallel isotopic shifts were found in deeper soils. However, these increased fractions of new carbon in SOC at the end of the experiment do not necessarily mean an increase in total SOC content, because gravimetric measurements of SOC did not reveal a significant increase under elevated [CO2Air], at least within the limits of SOC-content error bars. Thus, new carbon gains might be offset by pre-experiment carbon losses. The results demonstrate successful isotopic tracing of carbon from plants to soils in this sorghum FACE experiment showing differences between FACE and Control treatments, which suggest more dynamic cycling of SOC under elevated [CO2Air] than in the Control treatment. Published version

The Cascadia subduction zone hosts great $\mathrm{M}_\mathrm{W} > 8.5$ earthquakes, but studying these events is hindered by our short observational record. Earthquake cycle simulation provides an alternative window into the behavior of the subduction zone. Here, we present simulations over 3,800 years, 14 ruptures and hundreds of slow slip events on a high-fidelity geometric representation of the Cascadia subduction zone beneath surface topography. The boundaries of these ruptures are defined by ephemeral stress barriers that last for several cycles but are eliminated by a barrier-crossing rupture. Thus, it is possible that many real world rupture barriers are due to remnant stress shadows from previous slip events and may not persist over several earthquake cycles. In addition, we see ``fast' slow slip events with $\mathrm{M}_\mathrm{W} \approx 8$. These events may occur in nature and reduce the seismically available moment or they may be a spurious feature of an unrealistic friction law.

Boundary element methods have become a foundational tool in earthquake science for the modeling of earthquake cycle kinematics. Despite their wide use and convenience typical rectangular and triangular constant slip dislocation methods produce stress singularities at the edges of every element rendering these models physically unrealistic. As we demonstrate, in an earthquake cycle simulation where the stress influences the fault slip through a friction relationship, these un-physical stress singularities manifest in severe numerical artifacts which limit their applicability to the calculation of on fault stresses and dynamic earthquake cycle modeling. To solve this problem, we develop a singularity free Galerkin boundary element method using continuous linear displacement and slip basis functions. We use Gaussian and Sauter-Schwab quadrature combined with a Stokes theorem based regularization approach in lieu of analytical formulae. In order to solve the large dense linear systems that emerge from boundary element methods, we use a fast multipole method to accurately approximate far-field element interactions. Combining these theoretical approaches with an optimized parallel implementation and GPU acceleration, we are able to solve one million element problems in seconds on a desktop computer.

Disturbance regimes have a major influence on the baseline carbon that characterizes any particular ecosystem. Often regimes result in lower average regional baseline C (compared to those same systems if the disturbance processes were lessened/removed). However, in infrequently disturbed systems the role of disturbance as a "background" process that influences broad-scale, baseline C levels is often neglected. Long-term chronosequences suggest disturbances in these systems may serve to increase regional biomass C stocks by maintaining productivity. However, that inference has not been tested spatially. Here, the large forested system of southeast Alaska, USA, is utilized to 1) estimate baseline regional C stocks, 2) test the fundamental disturbance-ecosystem C relationship, 3) estimate the cumulative impact of disturbances on baseline C. Using 1491 ground points with carbon measurements and a novel way of mapping disturbance regimes, the relationship between total biomass C, disturbance exposure, and climate was analyzed statistically. A spatial model was created to determine regional C and compare different disturbance scenarios. In this infrequently disturbed ecosystem, higher disturbance exposure is correlated with higher biomass C, supporting the hypothesis that disturbances maintain productivity at broad scales. The region is estimated to potentially contain a baseline 1.21-1.52 Pg biomass C (when unmanaged). Removal of wind and landslides from the model resulted in lower net C stocks (-2 to -19% reduction), though the effect was heterogeneous on finer scales. There removal of landslides alone had a larger effect then landslide and wind combined removal. The relationship between higher disturbance exposure and higher biomass within the broad ecosystem (which, on average, has a very low disturbance frequency) suggest that disturbances can serve maintain higher levels of productivity in infrequently disturbed but very C dense ecosystems. Carbon research in other systems, especially those where disturbances are infrequent relative to successional processes, should consider the role of disturbances in maintaining baseline ecosystem productivity.

The purpose of this paper is to analyse the ongoing effects of a United Kingdom situated Doctor Leadership Development Programme (LDP) which used action learning (AL) as the vehicle of practice. The aims of the research are firstly to gain insights into the meanings given to the LDP experience two years on by a cohort of doctors with senior leadership roles. Secondly, to establish what the development tool applied, that of Action learning (AL), offered these senior doctors and their practice as they attempted to facilitate change. An interpretive design is applied and the research is context specific, capturing a local experience of leadership (e Cunha et al, 2017, Authors, 2018) over time. Participants were invited to take part in semi-structured interviews which were used as the data collection method. Study findings show that at a critical point for the organisation, the AL model of facilitation built a bridge between individual and collaborative action which has been sustained over time. In doing so new social support processes were created which enhanced the individual doctor’s leadership style to move towards that of a collective leadership model.

INTRODUCTION Patients with complex coronary artery disease and severe aortic stenosis unsuitable for conventional cardiac surgery pose a significant treatment challenge. This is especially difficult for patients where percutaneous revascularization is technically very challenging and/or would not offer as complete revascularisation compared to surgical revascularisation. In addition, patients who are unsuitable for transfemoral transcatheter aortic valve implantation (TAVI) pose an additional technical challenge, particularly with dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI). As a potential solution we describe the first case series of hybrid off-pump coronary artery bypass grafting (CABG) combined with transaortic TAVI. METHODS AND RESULTS Over a ten-month-period, four patients underwent hybrid off-pump CABG combined with transaortic TAVI. A full sternotomy allowed off-pump arterial and vein graft anastomosis to significantly stenosed coronaries. The first three patients had severe aorto-iliac disease precluding femoral access; the fourth patient was deemed unsuitable for PCI. Transaortic TAVI using Edwards Sapien 3 valves were performed without complication in all four patients. CONCLUSION The hybrid off-pump CABG and transaortic TAVI procedure allows for more complete coronary revascularization, negates the need for DAPT, and minimizes treatment delay of a TAVI procedure, particularly in patients unsuitable for transfemoral access. We propose this as an important treatment option for the heart team to consider. © 2016 Wiley Periodicals, Inc.

We report on a patient with an unusual cause of non-discogenic sciatica. A 48-year-old woman presented with a 10-day history of gradually worsening left buttock pain radiating to the ipsilateral posterior thigh and calf. She had a similar episode of less intense pain 8 months before which lasted about 2 months. She denied any history of antecedent trauma or back pain. MRI scan revealed a well-defined, fat-containing lesion of the left piriformis muscle similar to a lipoma displacing the sciatic nerve but not invading it. The sciatica was relieved after excision of the lesion. The patient remained asymptomatic after the operation. The present case suggested that an intrapiriformis lipoma can cause secondary piriformis syndrome and medical practitioners should be aware of this condition and consider lipomas and other occupying lesions of the pelvic muscles as a differential diagnosis in patients presenting with radicular pain.

Keith Clements, Ecumenical Dynamic: Living in More than One Place at Once. Geneva: World Council of Churches, 2013. Pp. 222. $20.00, paper. Together towards Life: Mission and Evangelism in Changing Landscapes, with a Practical Guide. Edited by Jooseop Keum. Geneva: World Council of Churches Publications, 2013. Pp. 81, with DVD. $ 20.00, paper. Michael Kinnamon, Can a Renewal Movement Be Renewed? Questions for the Future of Ecumenism. Grand Rapids, MI, and Cambridge, U.K.: William B. Eerdmans Publishing Co., 2014. Pp. 167. $24.00. After the Spring sparked by the ecumenical dialogues in the 1980's and 1990's, some now describe the ecumenical scene as one of Winter. The ecumenical accords hardly seem to have been noticed by the churches. Cardinal Walter Kasper suggested that the change may be the result of "unfulfilled expectations." But, the dialogues are only part of ecumenism, and two works here reviewed, by Clements and Kinnamon, both with long ecumenical experience, offer suggestions leading to a broader ecumenical vision. Clements, an English Baptist, was active in the Council of Churches for Britain and Ireland and the Conference of European Churches. His Ecumenical Dynamic proposes transcending narrow confines and entering into and identifying oneself with a dynamic that unites people. The central section of the work, "The Dynamic Illustrated," presents movements and individuals who represent this larger approach. Although the 1910 Edinburgh Conference is acknowledged as the beginning of the ecumenical movement, Clements suggests that it was the mutual visits, "the peace exchanges" of the Anglo-German churches in 1908 and 1909, when, as war clouds were rising, the historic voyages of two ships--one from England and the other from Germany, each with hundreds of Christians visiting their brothers and sisters of the other county--laid the foundation for the World Alliance for Promoting International Friendship. Other towering figures of this larger ecumenical vision were J. H. Oldham and "the Moot," a group of British intellectuals founded to explore the role of Christian belief in modern society and the relation between the social environment and the gospel; and George Bell, "the apostle of Unity," dean of Canterbury, for whom ecumenism was grounded in the sovereignty of Christ and expressed in personal relationships. The 1934 Barmen Declaration had ecumenical implications: It was not only a statement of faith but also an invitation to be identified with the Confessing Church. The last section, "The Dynamic Continued," looks to the future, one not dominated by ecclesial structures but with less-clericalized communities such as Taize, the Bruderhof, Focolare, Iona, and Corrymeela. …

An introduction comprising background and problem statement: There is a wide range of research into Patient Participation PP in healthcare 1, 2. However, certain areas of patient co-designed care remain under researched. One such area is organizational service delivery systems and models 2. While PP in organizational change management in healthcare remains almost unexplored. Unique access to an English Foundation Trust’s Lean service improvement programme SIP, enabled research which looks at whether/how the delivery of organizational change management in healthcare can be co-designed with the patient. Adopting the integrated care components of ‘Vision holistic perspective, organization and governance’ 3 the research captures tensions involved in fully involving the patient in their own care. Theory/Methods: Tensions in power, rationality and accountability/responsibility, examine and explain the patient’s role in the SIP. Ethnography empirically captures data relating to these tensions. Critical Action Research situates the research in the Trust’s organizational discourse. Results: To date the research offers dual insights into PP in organizational change management. Firstly, coterminous themes have been identified between PP and Lean theory which suggest existing organizational change management practices in healthcare are concomitant with theories of integrated care. Waste and value in systems efficiency; knowledge and perspective in strategy development; and organizational and healthcare boundaries, the traditional divide between roles and voice in co-designing care. Next, research into the patient’s role as a change agent in Lean organizational change management, suggests possible new Lean practices in healthcare, which work around patient participation. Discussions: PP in healthcare is already well established 1. Moral 4, 5, consequentialist 4, 6, epistemological and ontological 4, 6 and historical 7 perspectives and approaches have all been explored. Greater PP in their own care has a positive effect on patient 8 and organizational 6 outcomes. However, research into PP in healthcare organizational change management identifies further interesting areas of tension. Including the manifestation of coterminous themes and the boundaries organizational change management. Perspectives on the research’s theoretical rigour, place within the integrated care framework, limits and possible future research, will be discussed. Conclusions comprising key findings: For progress on integrated care aims the tensions between PP and organizational change management need to be explored and reconciled. For example, patient perspective, experience, specificity and voice may achieve healthcare improvements through contextual clarity and coherence of care. But the aim of zero-defect operating manifest in the SIP and patient safety goals to which healthcare organizational income is related, place these two positions at odds. This raises ontological and epistemological questions. Such as who or what structures drive patient service delivery outcomes power, who should make decisions on strategy development rationality and who or what is responsible for poor system efficiency responsibility and accountability. Suggestions for future research: Exploring capacities within care organisations to provide double-loop learning process redesign or deutero-learning learning to learn. 2; Overcoming barriers and integrating facilitators in cross-disciplinary groups 9 Orchestrating wider local governance which encompasses people’s integrative needs and perspectives 3

Patients with complex coronary artery disease and severe aortic stenosis unsuitable for conventional cardiac surgery pose a significant treatment challenge. This is especially difficult for patients where percutaneous revascularization is technically very challenging and/or would not offer as complete revascularisation compared to surgical revascularisation. In addition, patients who are unsuitable for transfemoral transcatheter aortic valve implantation (TAVI) pose an additional technical challenge, particularly with dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI). As a potential solution we describe the first case series of hybrid off-pump coronary artery bypass grafting (CABG) combined with transaortic TAVI.Over a ten-month-period, four patients underwent hybrid off-pump CABG combined with transaortic TAVI. A full sternotomy allowed off-pump arterial and vein graft anastomosis to significantly stenosed coronaries. The first three patients had severe aorto-iliac disease precluding femoral access; the fourth patient was deemed unsuitable for PCI. Transaortic TAVI using Edwards Sapien 3 valves were performed without complication in all four patients.The hybrid off-pump CABG and transaortic TAVI procedure allows for more complete coronary revascularization, negates the need for DAPT, and minimizes treatment delay of a TAVI procedure, particularly in patients unsuitable for transfemoral access. We propose this as an important treatment option for the heart team to consider. © 2016 Wiley Periodicals, Inc.