Complexes of a Noncyclic Carbazole-based N5-donor Schiff base: Structures, Redox, EPR and Poor Activity as Hydrogen Evolution Electrocatalysts.

A new noncyclic pentadentate N5-donor Schiff-base ligand, HL2Etpyr (1,1'-(3,6-ditert-butyl-9H-carbazole-1,8-diyl)bis(N-(2-(pyridin-2-yl)ethyl)methanimine)), prepared from 1,8-diformyl-3,6-ditertbutyl-carbazole (HUtBu) and two equivalents of 2-(2-pyridyl)ethylamine, along with four tetrafluoroborate complexes, [MIIL2Etpyr](BF4), where M = Co, Ni, Cu, and Zn, and two [CoIIL2EtPyr]·1/2[CoIIX4] complexes where X = NCS or Cl, isolated as solvates, are reported. All six complexes were structurally characterized, revealing the cations to be isostructural, with M(II) in a trigonal bipyramidal N5-donor environment. Only the Zn(II) complex is fluorescent. Cyclic voltammograms of [MIIL2Etpyr](BF4) in MeCN reveal reversible redox processes at positive potentials: 0.61 (Zn), 0.62 (Cu), 0.57 (Ni), and 0.25 V (Co), and for the cobalt complex a second quasi-reversible process occurs at 0.92 V vs Fc+/Fc. EPR data for the first oxidation product clearly demonstrate that the Zn complex undergoes a ligand centered oxidation, and support this being the case for the Ni and Cu complexes, although this is not definitively shown. After both oxidations the EPR data shows that the Co complex is best described as a low spin Co(III)-ligand radical. In the presence of 80 mM acetic acid, controlled potential electrolysis carried out on [MIIL2Etpyr](BF4) at -1.68 V in MeCN shows some electrocatalytic hydrogen evolution reaction (HER) performance in the order Ni(II) > Cu(II) > Co(II) - but the control, Ni(II) tetrafluoroborate, is more active than all three of the complexes.

"I am in favour of organ donation, but I feel you should opt-in"-qualitative analysis of the #options 2020 survey free-text responses from NHS staff toward opt-out organ donation legislation in England.

BACKGROUND: In May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey. METHODS: The #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed. RESULTS: The #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes. CONCLUSIONS: The overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings. TRIAL REGISTRATION: National Institute of Health Research (NIHR) [IRAS 275992].

Using oral bioaccessibility measurements to refine risk assessment of potentially toxic elements in topsoils across an urban area.

Elevated concentrations of As, Cr, Cu, Ni, Pb, V and Zn in topsoils in Belfast, Northern Ireland have been found to exceed assessment criteria in the city and therefore may pose a risk to human health. Most generic assessment criteria (GAC) for potentially toxic elements (PTEs) in soils assume PTEs are 100% bioavailable to humans. Here we use in-vitro oral bioaccessibility testing using the Unified BARGE method (UBM) to measure what proportion of soil contamination dissolves in the digestive tract and therefore is available for absorption by the body. This study considers how PTE bioaccessibility in soils varies spatially across urban areas and refines human health risk assessment for these PTEs using site specific oral bioaccessibility results to present the first regional assessment of risk that incorporates bioaccessibility testing. A total of 103 urban soil samples were selected for UBM testing. Results showed low bioaccessible fraction (BAF) for the PTEs from geogenic sources: Cr (0.45-5.9%), Ni (1.1-46.3%) and V (2.2-23.9%). Higher BAF values were registered for PTEs from anthropogenic sources: As (8.0-86.9%), Cu (3.4-67.8%), Pb (9.1-106.2%) and Zn (2.4-77.5%). Graphs of bioaccessibility adjusted assessment criteria (BAAC) were derived for each urban land use type and PTE. These provide a visual representation of the significance of oral bioaccessibility when deriving BAAC and how this is affected by 1) dominant exposure pathways for each land use and 2) relative harm posed from exposure to PTEs via each pathway, allowing oral bioaccessibility research to be targeted to contaminants and pathways that most significantly impact risk assessment. Pb was the most widespread contaminant with 16.5% of sites exceeding the Pb GAC. Applying BAAC did not significantly change risk evaluation for these samples as many had Pb BAF>50%. In contrast, all samples that exceeded the As GAC were found to no longer exceed a minimal level of risk when oral bioaccessibility was considered. Oral bioaccessibility testing resulted in a 45% reduction in the number of sites identified as posing a potential risk to human health.

Utilization and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study.

BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function. METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR). RESULTS: Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years. CONCLUSIONS: Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.

A propensity score-matched analysis indicates screening for asymptomatic coronary artery disease does not predict cardiac events in kidney transplant recipients.

Screening for asymptomatic coronary artery disease prior to kidney transplantation aims to reduce peri- and post-operative cardiac events. It is uncertain if this is achieved. Here, we investigated whether pre-transplant screening with a stress test or coronary angiogram associated with any difference in major adverse cardiac events (MACE) up to five years post-transplantation. We examined a national prospective cohort recruited to the Access to Transplant and Transplant Outcome Measures study who received a kidney transplant between 2011-2017, and linked patient demographics and details of cardiac screening investigations to outcome data extracted from the Hospital Episode Statistics dataset and United Kingdom Renal Registry. Propensity score matched groups were analyzed using Kaplan-Meier and Cox survival analyses. Overall, 2572 individuals were transplanted in 18 centers; 51% underwent screening and the proportion undergoing screening by center ranged from 5-100%. The incidence of MACE at 90 days, one and five years was 0.9%, 2.1% and 9.4% respectively. After propensity score matching based on the presence or absence of screening, 1760 individuals were examined (880 each in screened and unscreened groups). There was no statistically significant association between screening and MACE at 90 days (hazard ratio 0.80, 95% Confidence Interval 0.31-2.05), one year (1.12, 0.51-2.47) or five years (1.31, 0.86-1.99). Age, male sex and history of ischemic heart disease were associated with MACE. Thus, there is no association between screening for asymptomatic coronary artery disease and MACE up to five years post-transplant. Practices involving unselected screening of transplant recipients should be reviewed.

The Impact of Cold Ischaemia Time on Outcomes of Living Donor Kidney Transplantation in the UK Living Kidney Sharing Scheme.

OBJECTIVE: To assess the impact of CIT on living donor kidney transplantation (LDKT) outcomes in the UKLKSS versus outside the scheme. BACKGROUND: LDKT provides the best treatment option for end-stage kidney disease patients. end-stage kidney disease patients with an incompatible living donor still have an opportunity to be transplanted through Kidney Exchange Programmes (KEP). In KEPs where kidneys travel rather than donors, cold ischaemia time (CIT) can be prolonged. METHODS: Data from all UK adult LDKT between 2007 and 2018 were analysed. RESULTS: 9969 LDKT were performed during this period, of which 1396 (14%) were transplanted through the UKLKSS, which we refer to as KEP. Median CIT was significantly different for KEP versus non-KEP (339 versus 182 minutes, P < 0.001). KEP LDKT had a higher incidence of delayed graft function (DGF) (2.91% versus 5.73%, P < 0.0001), lower 1-year (estimated Glomerular Filtration Rate (eGFR) 57.90 versus 55.25 ml/min, P = 0.04) and 5-year graft function (eGFR 55.62 versus 53.09 ml/min, P = 0.01) compared to the non-KEP group, but 1- and 5-year graft survival were similar. Within KEP, a prolonged CIT was associated with more DGF (3.47% versus 1.95%, P = 0.03), and lower graft function at 1 and 5-years (eGFR = 55 vs 50 ml/min, P = 0.02), but had no impact on graft survival. CONCLUSION: Whilst CIT was longer in KEP, associated with more DGF and lower graft function, excellent 5-year graft survival similar to non-KEP was found.

Changing patterns of clinical decision making: are falling numbers of antibody incompatible transplants related to the increasing success of the UK Living Kidney Sharing Scheme? A national cohort study.

Antibody incompatibility is a barrier to living kidney transplantation; antibody incompatible transplantation (AIT) is an accepted treatment modality, albeit higher risk. This study aims to determine changes to clinical decision making and access to AIT in the UK. An electronic survey was sent to all UK renal transplant centres (n = 24), in 2014, and again in 2018. Questions focused on entry & duration in the UKLKSS for HLA and ABO-incompatible pairs, Can and provision of direct AIT transplantation within those centres. Between 2014 & 2018, the duration recommended for patients in the UKLKSS increased. In 2014, 34.8% of centres reported leaving HLA-i pairs in the UKLKSS indefinitely, or reviewing on a case by case basis, by 2018 this increased to 61%. Centres offering direct HLA-i transplantation reduced from 58% to 37%. For low titre (1:8) ABO-i recipients, 66% of centres recommended at least 9 months (3 matching runs) in the UKLKSS scheme in 2018, compared to 47% in 2014, 50% fewer units consider direct ABO-i transplantation for unsuccessful pairs with high ABO titres (>1:512). Over time, clinicians appear to be facilitating more conservative management of AIT patients, potentially limiting access to living donor transplantation.

Convalescent plasma therapy for the treatment of patients with COVID-19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels.

INTRODUCTION: The lack of approved specific therapeutic agents to treat coronavirus disease (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of a large-scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme-linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. METHODS: Blood samples were collected from 52 individuals with a previous laboratory-confirmed SARS-CoV-2 infection. These were assayed for SARS-CoV-2 nAbs by microneutralisation and pseudo-type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. RESULTS: All samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). DISCUSSION: Robust associations between nAb titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2 nAbs.

Predicting Humoral Alloimmunity from Differences in Donor and Recipient HLA Surface Electrostatic Potential.

In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure, but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesized that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared with recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level [three-dimensional electrostatic mismatch score (EMS-3D)]. We then examined humoral alloimmune responses in healthy females subjected to a standardized injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.

Convalescent plasma treatment for SARS-CoV-2 infection: analysis of the first 436 donors in England, 22 April to 12 May 2020.

Serological reactivity was analysed in plasma from 436 individuals with a history of disease compatible with COVID-19, including 256 who had been laboratory-confirmed with SARS-CoV-2 infection. Over 99% of laboratory-confirmed cases developed a measurable antibody response (254/256) and 88% harboured neutralising antibodies (226/256). Antibody levels declined over 3 months following diagnosis, emphasising the importance of the timing of convalescent plasma collections. Binding antibody measurements can inform selection of convalescent plasma donors with high neutralising antibody levels.

Limited health literacy is associated with reduced access to kidney transplantation.

Limited health literacy is common in patients with chronic kidney disease (CKD) and has been variably associated with adverse clinical outcomes. The prevalence of limited health literacy is lower in kidney transplant recipients than in individuals starting dialysis, suggesting selection of patients with higher health literacy for transplantation. We investigated the relationship between limited health literacy and clinical outcomes, including access to kidney transplantation, in a prospective UK cohort study of 2,274 incident dialysis patients aged 18-75 years. Limited health literacy was defined by a validated Single Item Literacy Screener (SILS). Multivariable regression was used to test for association with outcomes after adjusting for age, sex, socioeconomic status (educational level and car ownership), ethnicity, first language, primary renal diagnosis, and comorbidity. In fully adjusted analyses, limited health literacy was not associated with mortality, late presentation to nephrology, dialysis modality, haemodialysis vascular access, or pre-emptive kidney transplant listing, but was associated with reduced likelihood of listing for a deceased-donor transplant (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.51-0.90), receiving a living-donor transplant (HR 0.41; 95% CI 0.19-0.88), or receiving a transplant from any donor type (HR 0.65; 95% CI 0.44-0.96). Limited health literacy is associated with reduced access to kidney transplantation, independent of patient demographics, socioeconomic status, and comorbidity. Interventions to ameliorate the effects of low health literacy may improve access to kidney transplantation.

Transplantation of kidneys from DCD and DBD donors who died after ligature asphyxiation: The UK experience.

There is uncertainty about whether hypoxic injury accompanying donor death from ligature asphyxiation influences renal transplant outcomes, particularly for recipients of kidneys donated after circulatory death (DCD). The UK Registry analysis was undertaken to determine transplant outcomes in recipients of kidneys from donors who died following ligature asphyxiation. From 2003 to 2016, 2.7% (n = 521) of potential organ donors died following ligature asphyxiation (mostly suicide by hanging). Of these, 409 (78.5%) donated kidneys for transplantation (46.9% donation after brain death [DBD] and 53.1% DCD donors) resulting in 650 kidney transplants. Compared to other deceased donors, those dying from ligature asphyxiation were younger, more often male, and had less hypertension. Unadjusted patient and graft survival were superior for recipients of both DBD and DCD kidneys from donors dying after ligature asphyxiation, although after adjustment for donor/recipient variables, transplant outcomes were similar. A case-control matched analysis confirmed transplant outcomes for those who received kidneys from donors dying after ligature asphyxiation were similar to controls. Although caution is required in interpreting these findings because of potential selection bias, kidneys from donors dying of ligature asphyxiation suffer an additional warm ischemic insult that does not apparently adversely influence transplant outcomes, even for kidneys from DCD donors.

Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: a matched cohort analysis.

BACKGROUND: More than 40% of patients awaiting a kidney transplant in the UK are sensitised with human leucocyte antigen (HLA) antibodies. Median time to transplantation for such patients is double that of unsensitised patients at about 74 months. Removing antibody to perform an HLA-incompatible (HLAi) living donor transplantation is perceived to be high risk, although patient survival data are limited. We compared survival of patients opting for an HLAi kidney transplant with that of similarly sensitised patients awaiting a compatible organ. METHODS: From the UK adult kidney transplant waiting list, we selected crossmatch positive living donor HLAi kidney transplant recipients who received their transplant between Jan 1, 2007, and Dec 31, 2013, and were followed up to Dec 31, 2014 (end of study). These patients were matched in a 1:4 ratio with similarly sensitised patients cases listed for a deceased-donor transplant during that period. Data were censored both at the time of transplantation (listed only), and at the end of the study period (listed or transplant). We used Kaplan-Meier curves to compare patient survival between HLAi and the matched cohort. FINDINGS: Of 25 518 patient listings, 213 (1%) underwent HLAi transplantation during the study period. 852 matched controls were identified, of whom 41% (95% CI 32-50) remained without a transplant at 58 months after matching. We noted no difference in survival between patients who were in the HLAi group compared with the listed only group (log rank p=0·446), or listed or transplant group (log rank p=0·984). INTERPRETATION: Survival of sensitised patients undergoing HLAi in the UK is comparable with those on dialysis awaiting a compatible organ, many of whom are unlikely to be have a transplant. Choosing a direct HLAi transplant has no detrimental effect on survival, but offers no survival benefit, by contrast with similar patients studied in a North American multicentre cohort. FUNDING: UK National Health Service Blood & Transplant and Guy's & St Thomas' National Institute for Health Research Biomedical Research Centre.

Barriers to living donor kidney transplantation in the United Kingdom: a national observational study.

BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation.

Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L.

OBJECTIVES: To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors. METHODS: As part of the prospective observational study entitled "Access to Transplantation and Transplant Outcome Measures," we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients' health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores. RESULTS: EQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts. CONCLUSIONS: This study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease.

Limited health literacy in advanced kidney disease.

Limited health literacy may reduce the ability of patients with advanced kidney disease to understand their disease and treatment and take part in shared decision making. In dialysis and transplant patients, limited health literacy has been associated with low socioeconomic status, comorbidity, and mortality. Here, we investigated the prevalence and associations of limited health literacy using data from the United Kingdom-wide Access to Transplantation and Transplant Outcome Measures (ATTOM) program. Incident dialysis, incident transplant, and transplant wait-listed patients ages 18 to 75 were recruited from 2011 to 2013 and data were collected from patient questionnaires and case notes. A score >2 in the Single-Item Literacy Screener was used to define limited health literacy. Univariate and multivariate analyses were performed to identify patient factors associated with limited health literacy. We studied 6842 patients, 2621 were incident dialysis, 1959 were wait-listed, and 2262 were incident transplant. Limited health literacy prevalence was 20%, 15%, and 12% in each group, respectively. Limited health literacy was independently associated with low socioeconomic status, poor English fluency, and comorbidity. However, transplant wait-listing, preemptive transplantation, and live-donor transplantation were associated with increasing health literacy.

Transplantation of organs from deceased donors with meningitis and encephalitis: a UK registry analysis.

BACKGROUND: Deceased organ donors, where the cause of death is meningitis or encephalitis, are a potential concern because of the risks of transmission of a potentially fatal infection to recipients. METHODS: Using the UK Transplant Registry, a retrospective cohort analysis of deceased organ donors in the UK was undertaken to better understand the extent to which organs from deceased donors with meningitis and/or encephalitis (M/E) (of both known and unknown cause) have been used for transplantation, and to determine the associated recipient outcomes. RESULTS: Between 2003 and 2015, 258 deceased donors with M/E were identified and the causative agent was known in 188 (72.9%). These donors provided 899 solid organs for transplantation (455 kidneys and 444 other organs). The only recorded case of disease transmission was from a donor with encephalitis of unknown cause at time of transplantation who transmitted a fatal nematode infection to 2 kidney transplant recipients. A further 3 patients (2 liver and 1 heart recipient) died within 30 days of transplantation from a neurological cause (cerebrovascular accident) with no suggestion of disease transmission. Overall, patient and graft survival in recipients of organs from donors with M/E were similar to those for all other types of deceased organ donor. CONCLUSION: Donors dying with M/E represent a valuable source of organs for transplantation. The risk of disease transmission is low but, where the causative agent is unknown, caution is required.

Predicting patient survival after deceased donor kidney transplantation using flexible parametric modelling.

BACKGROUND: The influence of donor and recipient factors on outcomes following kidney transplantation is commonly analysed using Cox regression models, but this approach is not useful for predicting long-term survival beyond observed data. We demonstrate the application of a flexible parametric approach to fit a model that can be extrapolated for the purpose of predicting mean patient survival. The primary motivation for this analysis is to develop a predictive model to estimate post-transplant survival based on individual patient characteristics to inform the design of alternative approaches to allocating deceased donor kidneys to those on the transplant waiting list in the United Kingdom. METHODS: We analysed data from over 12,000 recipients of deceased donor kidney or combined kidney and pancreas transplants between 2003 and 2012. We fitted a flexible parametric model incorporating restricted cubic splines to characterise the baseline hazard function and explored a range of covariates including recipient, donor and transplant-related factors. RESULTS: Multivariable analysis showed the risk of death increased with recipient and donor age, diabetic nephropathy as the recipient's primary renal diagnosis and donor hypertension. The risk of death was lower in female recipients, patients with polycystic kidney disease and recipients of pre-emptive transplants. The final model was used to extrapolate survival curves in order to calculate mean survival times for patients with specific characteristics. CONCLUSION: The use of flexible parametric modelling techniques allowed us to address some of the limitations of both the Cox regression approach and of standard parametric models when the goal is to predict long-term survival.

Iron(II) spin crossover complexes of tetradentate Schiff-bases: tuning T1/2 by choice of formyl-heterocycle component.

Four new tetradentate Schiff-base ligands were prepared in situ from the 1 : 2 condensation of 1,3-diaminopropane and either 2-thiazolecarboxaldehyde (L2thiazole), 4-thiazolecarboxaldehyde (L4thiazole), 4-oxazolecarboxaldehyde (L4oxazole), or 5-bromopyridine-2-aldehyde (L5Br-pyridine), and complexed with [Fe(NCS)2(pyridine)4] to give four monometallic FeII complexes, [Fe(Lheterocycle)(NCS)2]. Structural characterisation shows the expected octahedral FeII centres in all cases, with Lheterocycle occupying the equatorial plane and the two thiocyanate ligands trans to each other, resulting in an N6 coordination sphere. Solid state magnetic measurements showed that the two complexes with the thiazole-based ligands exhibit the beginning of a spin transition above 300 K, with T1/2 = 350 K for [Fe(L4thiazole)(NCS)2] and 400 K for [Fe(L2thiazole)(NCS)2], whereas the 4-oxazole-based ligand gives [Fe(L4oxazole)(NCS)2] which remains high spin at all measured temperatures (50-400 K). Interestingly, [Fe(L5Br-pyridine)(NCS)2] crystallised as two solvent-free polymorphs: magnetic measurements on samples with both polymorphs present showed a two step SCO with an abrupt transition at T1/2 = 245 K assigned to the transition in polymorph A (as this was also seen in a sample of pure polymorph A), and a gradual transition at T1/2 = 304 K assigned to polymorph B. These findings show that the order of increasing ligand field strength for these heterocycles is 4-oxazole ≪ 5Br-pyridine < 4-thiazole < 2-thiazole.

Predictable electronic tuning of FeII and RuII complexes via choice of azine: correlation of ligand pKa with Epa(MIII/II) of complex.

Five new mononuclear ruthenium(II) tris-ligated complexes have been synthesised, varying through the choice of azine in the family of 3-azinyl-4-(4-methylphenyl)-5-phenyl-4H-1,2,4-triazole ligands (Lazine): [Ru(Lpyridine)](PF6)2 (1), [Ru(Lpyridazine)](PF6)2 (2), [Ru(L4-pyrimidine)](PF6)2 (3), [Ru(Lpyrazine)](PF6)2 (4), [Ru(L2-pyrimidine)](PF6)2 (5). Three of them, 1·2MeCN·Et2O, 3·2MeCN·Et2O and 4·2MeCN, have been structurally characterised, confirming the presence of the meridional isomer, as was previously reported for the FeII analogues. Cyclic voltammetry studies, in dry CH3CN vs. Ag/0.01 M AgNO3, show that all five RuII complexes undergo a reversible RuIII/RuII process, with the midpoint potential (Em) increasing from 0.87 to 1.18 V as the azine is changed: pyridine < pyridazine < 2-pyrimidine < 4-pyrimidine < pyrazine. A strong inverse linear correlation (R2 = 0.98) is found between the RuIII/RuII redox potential and the calculated HOMO orbital energies, which is consistent with the expectation that it is easier to oxidise (lower Em) a metal ion with a higher HOMO orbital energy. The same trend was reported earlier for the family of analogous FeII complexes, albeit at lower values of Em in all cases. In addition, the ionisation potentials of the RuII complexes, as well as those of the other group 8 analogues (FeII and OsII), showed a linear relationship with Epa. As the MIII/II redox potentials of a family of complexes has been previously reported to correlate with ligand pKa values, a computational protocol to calculate, in silico, the pKa of the Lazine family of ligands was developed. A strong linear relationship was found between the readily calculated pKa of the Lazine ligand and the Epa of the MII complex, for all three families of complexes (R2 = 0.98).