Treatment of Later Humoral Rejection with Anti-CD20 Monoclonal Antibody Rituximab: A Single Centre Experience

Humoral or vascular rejection is a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ that results in immune complex deposition on the vascular endothelium, activation of the complement cascade, production of endothelial dysfunction and regional ischaemic injury

COVID-19-exploring the implications of long-term condition type and extent of multimorbidity on years of life lost : a modelling study

Grant Information: David A. McAllister is wholly supported via an intermediate clinical fellowship from the Wellcome Trust (201492). Peter Hanlon is funded through a Clinical Research Training Fellowship from the Medical Research Council (MR/S021949/1).Background: COVID-19 is responsible for increasing deaths globally. As most people dying with COVID-19 are older with underlying long-term conditions (LTCs), some speculate that YLL are low. We aim to estimate YLL attributable to COVID-19, before and after adjustment for number/type of LTCs, using the limited data available early in the pandemic. Methods: We first estimated YLL from COVID-19 using WHO life tables, based on published age/sex data from COVID-19 deaths in Italy. We then used aggregate data on number/type of LTCs in a Bayesian model to estimate likely combinations of LTCs among people dying with COVID-19. We used routine UK healthcare data from Scotland and Wales to estimate life expectancy based on age/sex/these combinations of LTCs using Gompertz models from which we then estimate YLL. Results: Using the standard WHO life tables, YLL per COVID-19 death was 14 for men and 12 for women. After adjustment for number and type of LTCs, the mean YLL was slightly lower, but remained high (11.6 and 9.4 years for men and women, respectively). The number and type of LTCs led to wide variability in the estimated YLL at a given age (e.g. at ≥80 years, YLL was >10 years for people with 0 LTCs, and <3 years for people with ≥6). Conclusions: Deaths from COVID-19 represent a substantial burden in terms of per-person YLL, more than a decade, even after adjusting for the typical number and type of LTCs found in people dying of COVID-19. The extent of multimorbidity heavily influences the estimated YLL at a given age. More comprehensive and standardised collection of data (including LTC type, severity, and potential confounders such as socioeconomic-deprivation and care-home status) is needed to optimise YLL estimates for specific populations, and to understand the global burden of COVID-19, and guide policy-making and interventions.Peer reviewe

Integrated AMP-PAN, TRUEX, and SREX Flowsheet Test to Remove Cesium, Surrogate Actinide Elements, and Strontium from INEEL Tank Waste Using Sorbent Columns and Centrifugal Contactors

Three unit operations for the removal of selected fission products, actinides, and RCRA metals (mercury and lead) have been successfully integrated and tested for extended run times with simulated INEEL acidic tank waste. The unit operations were ion exchange for Cs removal, followed by TRUEX solvent extraction for Eu (actinide surrogate), Hg, and Re (Tc surrogate) removal, and subsequent SREX solvent extraction for Sr and Pb removal. Approximately 45 L of simulated INTEC tank waste was first processed through three ion exchange columns in series for selective Cs removal. The columns were packed with a composite ammonium molybdophosphate-polyacrylonitrile (AMP-PAN) sorbent. The experimental breakthrough data were in excellent agreement with modeling predictions based on data obtained with much smaller columns. The third column (220 cm3) was used for polishing and Cs removal after breakthrough of the up-stream columns. The Cs removal was >99.83% in the ion exchange system without interference from other species. Most of the effluent from the ion exchange (IX) system was immediately processed through a TRUEX solvent extraction flowsheet to remove europium (americium surrogate), mercury and rhenium (technetium surrogate) from the simulated waste. The TRUEX flowsheet test was performed utilizing 23 stages of 3.3-cm centrifugal contactors. Greater than 99.999% of the Eu, 96.3% of the Hg, and 56% of the Re were extracted from the simulated feed and recovered in the strip and wash streams. Over the course of the test, there was no detectable build-up of any components in the TRUEX solvent. The raffinate from the TRUEX test was stored and subsequently processed several weeks later through a SREX solvent extraction flowsheet to remove strontium, lead, and Re (Tc surrogate) from the simulated waste. The SREX flowsheet test was performed using the same centrifugal contactors used in the TRUEX test after reconfiguration and the addition of three stages. Approximately 99.9% of the Sr, >99.89% of the Pb, and >96.4% of the Re were extracted from the aqueous feed to the SREX flowsheet and recovered in the strip and wash sections. Approximately 41 L of simulated tank waste (based on the volume processed through the TRUEX flowsheet) was processed through the integrated flowsheet and resulted in 175 L of liquid high activity waste (HAW) and 219.6 L of liquid low activity waste (LAW). The HAW fraction would be evaporated, dried and subsequently vitrified for final disposal. Based on current baseline assumptions, including a maximum phosphate loading of 2.5 wt. % in the HAW glass, the flowsheet tested would result in the production 0.195 kg of glass per L of tank waste processed. The LAW fraction would be solidified (via evaporation and denitration) and subsequently grouted. The current baseline assumptions for grouting the LAW stream indicate 0.37 kg of grout would be produced per L of tank waste treated. Under these assumptions, treating the current inventory of ~5E+6 L (5,000 m3) of tank waste would result in 375 m3 of HAW glass and 1,135 m3 of LAW Class A performance grout. The HAW glass volume could be significantly decreased by suitable TRUEX flowsheet modifications

"Black Streak" in western hemlock : its characteristics and influence on strength

Information reviewed and reaffirmed

COVID-19 – exploring the implications of long-term condition type and extent of multimorbidity on years of life lost: a modelling study

Background: COVID-19 is responsible for increasing deaths globally. As most people dying with COVID-19 are older with underlying long-term conditions (LTCs), some speculate that YLL are low. We aim to estimate YLL attributable to COVID-19, before and after adjustment for number/type of LTCs, using the limited data available early in the pandemic. Methods: We first estimated YLL from COVID-19 using WHO life tables, based on published age/sex data from COVID-19 deaths in Italy. We then used aggregate data on number/type of LTCs in a Bayesian model to estimate likely combinations of LTCs among people dying with COVID-19. We used routine UK healthcare data from Scotland and Wales to estimate life expectancy based on age/sex/these combinations of LTCs using Gompertz models from which we then estimate YLL. Results: Using the standard WHO life tables, YLL per COVID-19 death was 14 for men and 12 for women. After adjustment for number and type of LTCs, the mean YLL was slightly lower, but remained high (11.6 and 9.4 years for men and women, respectively). The number and type of LTCs led to wide variability in the estimated YLL at a given age (e.g. at ≥80 years, YLL was &gt;10 years for people with 0 LTCs, and &lt;3 years for people with ≥6). Conclusions: Deaths from COVID-19 represent a substantial burden in terms of per-person YLL, more than a decade, even after adjusting for the typical number and type of LTCs found in people dying of COVID-19. The extent of multimorbidity heavily influences the estimated YLL at a given age. More comprehensive and standardised collection of data (including LTC type, severity, and potential confounders such as socioeconomic-deprivation and care-home status) is needed to optimise YLL estimates for specific populations, and to understand the global burden of COVID-19, and guide policy-making and interventions

A Modeling Framework to Describe the Transmission of Bluetongue Virus within and between Farms in Great Britain

Recently much attention has been given to developing national-scale micro-simulation models for livestock diseases that can be used to predict spread and assess the impact of control measures. The focus of these models has been on directly transmitted infections with little attention given to vector-borne diseases such as bluetongue, a viral disease of ruminants transmitted by Culicoides biting midges. Yet BT has emerged over the past decade as one of the most important diseases of livestock.We developed a stochastic, spatially-explicit, farm-level model to describe the spread of bluetongue virus (BTV) within and between farms. Transmission between farms was modeled by a generic kernel, which includes both animal and vector movements. Once a farm acquired infection, the within-farm dynamics were simulated based on the number of cattle and sheep kept on the farm and on local temperatures. Parameter estimates were derived from the published literature and using data from the outbreak of bluetongue in northern Europe in 2006. The model was validated using data on the spread of BTV in Great Britain during 2007. The sensitivity of model predictions to the shape of the transmission kernel was assessed.The model is able to replicate the dynamics of BTV in Great Britain. Although uncertainty remains over the precise shape of the transmission kernel and certain aspects of the vector, the modeling approach we develop constitutes an ideal framework in which to incorporate these aspects as more and better data become available. Moreover, the model provides a tool with which to examine scenarios for the spread and control of BTV in Great Britain

Changing spaces of political encounter and the rise of anti-politics: evidence from Mass Observation's General Election diaries

Negativity towards the institutions of formal politics is currently a concern across much of the democratic world. It is generally agreed that such negativity increased among British citizens during the second half of the twentieth century. In this paper, we analyse a novel dataset not previously used to study this topic: Mass Observation's General Election diaries. Since diarists wrote mostly about politicians, political campaigns, and associated media coverage, we ask specifically what the diaries can tell us about increased negativity towards politicians and its relationship to developments in political communication. We take a postholing approach to sampling of the diaries, enabling comparative-static analysis between the middle and end of the twentieth century. We view the diaries in a geographical framework derived from contextual theories of social action. This gives us a focus on spaces of political encounter, modes of political interaction, performances by politicians, and judgements by citizens. We argue that prominent spaces of political encounter changed over the period from long radio speeches and rowdy political meetings to televised debates and associated expert commentary. We demonstrate how these latter settings for political interaction afforded less opportunity for politicians to perform virtues to citizens, and for citizens to calibrate judgements of politicians

Chronic infarct size after spontaneous coronary artery dissection: implications for pathophysiology and clinical management

Aims: To report the extent and distribution of myocardial injury and its impact on left ventricular systolic function with cardiac magnetic resonance imaging (CMR) following spontaneous coronary artery dissection (SCAD) and to investigate predictors of myocardial injury. Methods and results: One hundred and fifty-eight angiographically confirmed SCAD-survivors (98% female) were phenotyped by CMR and compared in a case–control study with 59 (97% female) healthy controls (44.5 ± 8.4 vs. 45.0 ± 9.1 years). Spontaneous coronary artery dissection presentation was with non-ST-elevation myocardial infarction in 95 (60.3%), ST-elevation myocardial infarction (STEMI) in 52 (32.7%), and cardiac arrest in 11 (6.9%). Left ventricular function in SCAD-survivors was generally well preserved with small reductions in ejection fraction (57 ± 7.2% vs. 60 ± 4.9%, P &lt; 0.01) and increases in left ventricular dimensions (end-diastolic volume: 85 ± 14 mL/m2 vs. 80 ± 11 mL/m2, P &lt; 0.05; end-systolic volume: 37 ± 11 mL/m2 vs. 32 ± 7 mL/m2, P &lt;0.01) compared to healthy controls. Infarcts were small with few large infarcts (median 4.06%; range 0–30.9%) and 39% having no detectable late gadolinium enhancement (LGE). Female SCAD patients presenting with STEMI had similar sized infarcts to female Type-1 STEMI patients age &lt;75 years. Multivariate modelling demonstrated STEMI at presentation, initial TIMI 0/1 flow, multivessel SCAD, and a Beighton score &gt;4 were associated with larger infarcts [&gt;10% left ventricular (LV) mass]. Conclusion: The majority of patients presenting with SCAD have no or small infarctions and preserved ejection fraction. Patients presenting with STEMI, TIMI 0/1 flow, multivessel SCAD and those with features of connective tissue disorders are more likely to have larger infarcts

Patient-Reported Outcomes and Socioeconomic Status as Predictors of Clinical Outcomes after Hematopoietic Stem Cell Transplantation: A Study from the Blood and Marrow Transplant Clinical Trials Network 0902 Trial

This secondary analysis of a large, multi-center Blood and Marrow Transplant Clinical Trials Network (BMT CTN) randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pre-transplant Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores (MCS and PCS) of the SF-36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (p<.01 considered significant given multiple testing). Lower attained education was associated with increased distress (p=.002); lower income was related to worse physical functioning (p=.005) and increased distress (p=.008); lack of employment pre-transplant was associated with worse physical functioning (p<.01); unmarried status was associated with worse sleep (p=.003). In this large heterogeneous cohort of HCT recipients, while PROs and SES variables were correlated at baseline, they were not associated with any clinical outcomes. Future research should focus on HCT recipients at greater psychosocial disadvantage