Connectivity properties of moment maps on based loop groups

For a compact, connected, simply-connected Lie group G, the loop group LG is the infinite-dimensional Hilbert Lie group consisting of H^1-Sobolev maps S^1-->G. The geometry of LG and its homogeneous spaces is related to representation theory and has been extensively studied. The space of based loops Omega(G) is an example of a homogeneous space of $LG$ and has a natural Hamiltonian T x S^1 action, where T is the maximal torus of G. We study the moment map mu for this action, and in particular prove that its regular level sets are connected. This result is as an infinite-dimensional analogue of a theorem of Atiyah that states that the preimage of a moment map for a Hamiltonian torus action on a compact symplectic manifold is connected. In the finite-dimensional case, this connectivity result is used to prove that the image of the moment map for a compact Hamiltonian T-space is convex. Thus our theorem can also be viewed as a companion result to a theorem of Atiyah and Pressley, which states that the image mu(Omega(G)) is convex. We also show that for the energy functional E, which is the moment map for the S^1 rotation action, each non-empty preimage is connected.Comment: This is the version published by Geometry & Topology on 28 October 200

Overview of the Evolution of the UK Kidney Allocation Schemes

Abstract: Purpose of Review: Allocation of deceased donor kidneys for transplantation has evolved since the first utilitarian approach in 1989. This review looks at how the schemes have evolved over the ensuing three decades. Recent Findings: Four kidney offering schemes have been used in the last 30 years. Successive schemes have evolved from offering only one donor kidney for a nationally prioritised patient to offering both kidneys, from addressing only kidneys from donors after brain death (DBD) to offering kidneys from both DBD and circulatory death donors (DCD) and from prioritising purely on the basis of zero class 2 and minimising class 1 mismatches to a more relaxed approach for older donors and more difficult to match patients while introducing the concept of longevity matching. Summary: UK kidney offering schemes have evolved through a series of evidence-based analyses to try to optimally address the principles of utility and fairness in kidney offering

Overview of the Evolution of the UK Kidney Allocation Schemes

Abstract: Purpose of Review: Allocation of deceased donor kidneys for transplantation has evolved since the first utilitarian approach in 1989. This review looks at how the schemes have evolved over the ensuing three decades. Recent Findings: Four kidney offering schemes have been used in the last 30 years. Successive schemes have evolved from offering only one donor kidney for a nationally prioritised patient to offering both kidneys, from addressing only kidneys from donors after brain death (DBD) to offering kidneys from both DBD and circulatory death donors (DCD) and from prioritising purely on the basis of zero class 2 and minimising class 1 mismatches to a more relaxed approach for older donors and more difficult to match patients while introducing the concept of longevity matching. Summary: UK kidney offering schemes have evolved through a series of evidence-based analyses to try to optimally address the principles of utility and fairness in kidney offering

Utilization and Outcomes of Single and Dual Kidney Transplants from Older Deceased Donors in the United Kingdom

BACKGROUND AND OBJECTIVES: Kidneys from elderly deceased donors are often discarded after procurement if the expected outcomes from single kidney transplantation are considered unacceptable. An alternative is to consider them for dual kidney transplantation. We aimed to examine the utilization of kidneys from donors aged ≥60 years in the United Kingdom and compare clinical outcomes of dual versus single kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the United Kingdom Transplant Registry from 2005 to 2017 were analyzed. We examined utilization rates of kidneys retrieved from deceased donors aged ≥60 years, and 5-year patient and death-censored graft survival of recipients of dual and single kidney transplants. Secondary outcomes included eGFR. Multivariable analyses and propensity score analysis were used to correct for differences between the groups. RESULTS: During the study period, 7841 kidneys were procured from deceased donors aged ≥60 years, of which 1338 (17%) were discarded; 356 dual and 5032 single kidneys were transplanted. Donors of dual transplants were older (median, 73 versus 66 years; P<0.001) and had higher United States Kidney Donor Risk Indices (2.48 versus 1.98; P<0.001). Recipients of dual transplants were also older (64 versus 61 years; P<0.001) and had less favorable human leukocyte antigen matching (P<0.001). After adjusting for confounders, dual and single transplants had similar 5-year graft survival (hazard ratio, 0.81; 95% CI, 0.59 to 1.12). No difference in patient survival was demonstrated. Similar findings were observed in a matched cohort with a propensity score analysis method. Median 12-month eGFR was significantly higher in the dual kidney transplant group (40 versus 36 ml/min per 1.73 m(2); P<0.001). CONCLUSIONS: Recipients of kidneys from donors aged ≥60 years have similar 5-year graft survival and better graft function at 12 months with dual compared with single deceased donor kidney transplants

Comparison of medium-term outcomes of living Kidney donors with longitudinal healthy control in the U.K

BACKGROUND: Understanding the outcomes and risks for live kidney donors is increasingly important; this study investigated all-cause mortality and morbidity outcomes of live kidney donors compared with healthy cohort. METHODS: Live donor dataset was obtained from UK Transplant Registry and a comparator nondonor cohort selected from The Health Improvement Network (THIN) database, a UK primary healthcare database. All live kidney donors (LD) from 1 January 2001 to 31 December, 2013 were included, with follow-up until 31 December 2016. RESULTS: There were 9750 LD and 19 071 THIN participants. Median follow up (IQR) for LD was 8.4 (6.0 to 11.3) years & THIN 5.4 (2.6 to 8.5) years. In up to 15 years follow-up end stage renal disease (ESRD) was observed in 1 LD versus 7 THIN (P=0.280). Nine LD had eGFR<30ml/min/1.73m versus 43 in THIN (P=0.012), but no statistically significant difference in adjusted logistic regression analyses. Risk of diabetes, depression and cardiovascular disease was significantly higher for THIN cohort in adjusted analyses. The risk of hypertension was higher for LD at 5 years, but was not significantly different in fully adjusted analyses at 10 years. There were 68 deaths in LD and 485 in THIN over the follow-up period, with significant difference in mortality favoring LD (P<0.001). CONCLUSIONS: The medium-term morbidity and mortality outcomes of live donors in comparison with a healthy cohort suggest that live donation is not associated with excess mortality, ESRD or morbidity, in at least 10 years follow-up

Blood transfusions post kidney transplantation are associated with inferior allograft and patient survival—it is time for rigorous patient blood management

BackgroundPatient Blood Management (PBM), endorsed by the World Health Organisation is an evidence-based, multi-disciplinary approach to minimise inappropriate blood product transfusions. Kidney transplantation presents a particular challenge to PBM, as comprehensive evidence of the risk of transfusion is lacking. The aim of this study is to investigate the prevalence of post-transplant blood transfusions across multiple centres, to analyse risk factors for transfusion and to compare transplant outcomes by transfusion status.MethodsThis analysis was co-ordinated via the UK Transplant Registry within NHS Blood and Transplant (NHSBT), and was performed across 4 centres. Patients who had received a kidney transplant over a 1-year period, had their transfusion status identified and linked to data held within the national registry.ResultsOf 720 patients, 221(30.7%) were transfused, with 214(29.7%) receiving a red blood cell (RBC) transfusion. The proportion of patients transfused at each centre ranged from 20% to 35%, with a median time to transfusion of 4 (IQR:0-12) days post-transplant. On multivariate analysis, age [OR: 1.02(1.01-1.03), p=0.001], gender [OR: 2.11(1.50-2.98), p&lt;0.0001], ethnicity [OR: 1.28(1.28-2.60), p=0.0008], and dialysis dependence pre-transplant [OR: 1.67(1.08-2.68), p=0.02], were associated with transfusion. A risk-adjusted Cox proportional hazards model showed transfusion was associated with inferior 1-year patient survival [HR 7.94(2.08-30.27), p=0.002] and allograft survival [HR: 3.33(1.65-6.71), p=0.0008], and inferior allograft function.ConclusionRBC transfusions are common and are independently associated with inferior transplant outcomes. We urge that further research is needed to understand the mechanisms behind the outcomes, to support the urgent development of transplant-specific anaemia guidelines

The impact of the SARS‐CoV‐2 pandemic and COVID‐19 on lung transplantation in the UK: Lessons learned from the first wave

BACKGROUND: Lung transplantation is particularly susceptible to the impact of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, and evaluation of changes to practice is required to inform future decision-making. METHODS: A retrospective review of the UK Transplant Registry (UKTR) and national survey of UK lung transplant centers has been performed. RESULTS: There was geographic variation in the prevalence of COVID-19 infection across the UK. The number of donors fell by 48% during the early pandemic period. Lung utilization fell to 10% (compared with 24% for the same period of 2019). The number of lung transplants performed fell by 77% from 53, March to May 2019, to 12. Seven (58%) of these were performed in a single-center, designated "COVID-light." The number of patients who died on the lung transplant waiting list increased, compared to the same period of 2019 (p = .0118). Twenty-six lung transplant recipients with confirmed COVID-19 infection were reported during the study period. CONCLUSION: As the pandemic continues, reviewing practice and implementing the lessons learned during this period, including the use of robust donor testing strategies and the provision of "COVID-light" hospitals, are vital in ensuring the safe continuation of our lung transplant program

Antibody prevalence after three or more COVID-19 vaccine doses in individuals who are immunosuppressed in the UK: a cross-sectional study from MELODY

SummaryBackground In the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARSCoV-2 spike protein with demographic, disease, and treatment- related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed.Methods In a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine. The study was open to recruitment from Dec 7, 2021, to June 26, 2022. Participants received a lateral flow immunoassay test for SARS-CoV-2 spike antibodies to complete at home, and an online questionnaire. Multivariable logistic regression was used to estimate the mutually adjusted odds of seropositivity against each characteristic.FindingsBetween Feb 14 and June 26, 2022, we screened 101 972 people (98 725 invited, 3247 self-enrolled) and recruited 28 411 (27·9%) to the study. 23 036 (81·1%) recruited individuals provided serological data. Of these, 9927 (43·1%) were recipients of solid organ transplants, 6516 (28·3%) had rare autoimmune rheumatic diseases, and 6593 (28·6%) had lymphoid malignancies. 10 485 (45·5%) participants were men and 12 535 (54·4%) were women (gender was not reported for 16 [<0·1%] participants), and 21661 (94·0%) participants were of White ethnicity. The median age of participants with solid organ transplants was 60 years (SD 50–67), with rare autoimmune rheumatic diseases was 65 years (54–73), and with lymphoid malignancy was 69 years (61–75). Of the 23 036 participants with serological data, 6583 (28·6%) had received three vaccine doses, 14 234 (61·8%) had received four vaccine doses, and 2219 (9·6%) had received five or more vaccine doses. IgG anti-spike antibodies were undetectable in 2310 (23·3%) of 9927 patients with solid organ transplants, 922 (14·1%) of 6516 patients with rare autoimmune rheumatic diseases, and 1366 (20·7%) of 6593 patients with lymphoid malignancies. In all groups, seropositivity was associated with younger age, higher number of vaccine doses (ie, five vs three), and previous COVID-19. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in recipients of solid organ transplants receiving a combination of an anti-proliferative agent, a calcineurin inhibitor, and steroids, and those with rare autoimmune rheumatic diseases or lymphoid malignancies treated with anti-CD20 therapies. InterpretationApproximately one in five recipients of solid organ transplants, individuals with rare autoimmune rheumatic diseases, and individuals with lymphoid malignancies have no detectable IgG anti-spike antibodies despite three or more vaccine doses, but this proportion decreases with sequential booster doses. Choice of immunosuppressant and disease type is strongly associated with serological response. Antibody testing using lateral flow immunoassay tests could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions