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1.
Sci Adv ; 6(32): eaba0697, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32821818

RESUMO

Microbial cells buried in subseafloor sediments comprise a substantial portion of Earth's biosphere and control global biogeochemical cycles; however, the rate at which they use energy (i.e., power) is virtually unknown. Here, we quantify organic matter degradation and calculate the power utilization of microbial cells throughout Earth's Quaternary-age subseafloor sediments. Aerobic respiration, sulfate reduction, and methanogenesis mediate 6.9, 64.5, and 28.6% of global subseafloor organic matter degradation, respectively. The total power utilization of the subseafloor sediment biosphere is 37.3 gigawatts, less than 0.1% of the power produced in the marine photic zone. Aerobic heterotrophs use the largest share of global power (54.5%) with a median power utilization of 2.23 × 10-18 watts per cell, while sulfate reducers and methanogens use 1.08 × 10-19 and 1.50 × 10-20 watts per cell, respectively. Most subseafloor cells subsist at energy fluxes lower than have previously been shown to support life, calling into question the power limit to life.

2.
J Environ Radioact ; 198: 189-199, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30640033

RESUMO

The spectrum of cosmogenic neutrons at Earth's surface covers a wide energy range, from thermal to several GeV. The flux of secondary neutrons varies with latitude, elevation, solar activity, and nearby material, including ground moisture. We report the results from a campaign to measure count rates in neutron detectors responding to three different energy ranges conducted near the geomagnetic North Pole at CFS Alert, Nunavut, Canada (82.5°N, 62.5°W; vertical geomagnetic cutoff rigidity, RC = 0 GV) in June of 2016. In November 2016, we performed a follow-on measurement campaign in southern Canada at similar RC (1.5 GV) and elevations. We conducted these measurements, at varying elevation and ground moisture content, with unmoderated and moderated 3He detectors for thermal and epithermal-to-MeV sensitivity, and with EJ-299-33 pulse shape discrimination plastic scintillator detectors for fast neutrons. Background gamma rays were monitored with NaI(Tl) detectors. Using these data sets, we compared the measured count rates to a predictive model. This is the first ever data set taken from this location on Earth. We find that for the thermal and epithermal-to-MeV neutron measurements the predictive model and data are in good agreement, except at one location on rock-covered ground near 1 km elevation. The discrepancy at that location may be attributable to ground moisture variability. Other measurements, during this campaign and prior, support the assertion that ground moisture plays a critical role in determining neutron flux.


Assuntos
Radiação Cósmica , Monitoramento de Radiação , Regiões Árticas , Canadá , Raios gama , Nêutrons , Atividade Solar
3.
Am J Transplant ; 17(3): 796-802, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27935215

RESUMO

Transplant-mediated alloimmune thrombocytopenia (TMAT) from donors with immune thrombocytopenia (ITP) can result in significant bleeding complications in the recipient. The risk to a recipient of TMAT if they receive an organ from a donor with ITP is unknown. The outcomes of recipients of organs from deceased donors with ITP recorded in the UK Transplant Registry between 2000 and 2015 were reviewed. Twenty-one deceased organ donors had a predonation diagnosis of ITP. These donors were significantly more likely to have died from intracranial hemorrhage than were all other deceased organ donors (85% vs. 57%, p < 0.001). Organs from donors with ITP resulted in 49 organ transplants (31 kidney, 14 liver, four heart), with only one case of TMAT, which occurred in a liver transplant recipient and resulted in death from bleeding complications 18 days posttransplantation. The recipient of a kidney from the same organ donor was not affected. Unadjusted 5-year patient and graft survival was significantly worse for liver transplant recipients from donors with ITP compared with liver transplant recipients from donors without ITP (64% vs. 85%, p = 0.012). Organs from donors with ITP may be considered for transplantation, but livers should be used with caution.


Assuntos
Rejeição de Enxerto/etiologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/imunologia , Púrpura Trombocitopênica Idiopática/imunologia , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Transplantados , Adulto , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
Am J Transplant ; 17(2): 390-400, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27428662

RESUMO

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002-2003 and 2011-2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney-only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p < 0.0001), listed patients at our center waited less time for transplantation (645 vs. 1045 days; p < 0.0001), and our center had higher transplantation rates and lower numbers of waiting list deaths. This was most apparent for older patients (aged >65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death-censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients.


Assuntos
Morte Encefálica , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Transplante de Rim , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Listas de Espera , Idoso , Cadáver , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Reino Unido
5.
Health Phys ; 110(5): 458-70, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27023033

RESUMO

A series of experiments was conducted in 2012 at the Defence Research and Development Canada's Suffield Research Centre in Alberta, Canada, during which three radiological dispersal devices were detonated. The detonations released radioactive (140)La into the air, which was then carried by winds and detectable over distances of up to 2 km. The Nuclear Emergency Response group of Natural Resources Canada conducted airborne radiometric surveys shortly following the explosions to map the pattern of radioactivity deposited on the ground. The survey instrument suite was based on large volume NaI(Tl) scintillation gamma radiation detectors, which were situated in a basket mounted exterior to the helicopter and oriented end-to-end to maximize the sensitivity. A standard geophysical data treatment was used to subtract backgrounds and to correct the data to produce counts due to (140)La at the nominal altitude. Sensitivity conversion factors obtained from Monte Carlo simulations were then applied to express the measurements in terms of surface activity concentration in kBq m(-2). Integrated over the survey area, the results indicate that only 20 to 25% of the bomb's original inventory of radioactive material is deposited within a 1.5-km radius of ground zero. These results can be accommodated with a simple model for the RDD behavior and atmospheric dispersion.


Assuntos
Poluentes Radioativos do Ar/análise , Aeronaves , Raios gama , Lantânio/análise , Monitoramento de Radiação/instrumentação , Liberação Nociva de Radioativos , Canadá , Explosões , Humanos , Modelos Teóricos , Método de Monte Carlo , Doses de Radiação , Monitoramento de Radiação/métodos
6.
Am J Transplant ; 16(7): 2139-47, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26755448

RESUMO

We have assessed whether HLA immunogenicity as defined by differences in donor-recipient HLA amino-acid sequence (amino-acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor-recipient HLA mismatch to induce donor-specific antibody (DSA). HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02-2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02-1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA-DR and HLA-DQ DSA, but only EMS correlated with the risk of HLA-A and -B DSA development. Differences in donor-recipient HLA amino-acid sequence and physicochemical properties enable better assessment of the risk of HLA-specific sensitization than conventional HLA matching.


Assuntos
Rejeição de Enxerto/diagnóstico , Antígenos HLA-DQ/imunologia , Antígenos HLA-DR/imunologia , Isoanticorpos/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Adulto , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Teste de Histocompatibilidade , Humanos , Testes de Função Renal , Masculino , Prognóstico , Fatores de Risco , Transplantados
7.
Clin Radiol ; 70(11): 1220-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26194860

RESUMO

AIM: To examine the usage and value of computed tomography (CT) following simultaneous pancreas and kidney (SPK) transplantation. MATERIALS AND METHODS: Indications for postoperative CT, key findings, and their influence on management were determined by retrospective analysis. RESULTS: Ninety-eight patients underwent 313 CT examinations. Common indications for the examinations included suspected intra-abdominal collection (31.1%) and elevated serum amylase/lipase (24.1%). CT findings most frequently showed non-specific mild inflammation (27.6%), a normal scan (17.1%) and fluid collections (16.3%). High capillary blood glucose (CBG) was associated with resultant CT demonstration of graft vascular abnormalities, but otherwise, particular clinical indications were not associated with specific CT findings. CONCLUSION: Clinical findings in patients with SPK transplants are non-specific. The pattern of abnormalities encountered is significantly different to those seen in native pancreatic disease and demands a tailored protocol. CT enables accurate depiction of vascular abnormalities and fluid collections, thus reducing the number of surgical interventions that might otherwise be required. Elevated CBG should prompt urgent CT to exclude potentially reversible vascular complications.


Assuntos
Transplante de Pâncreas/métodos , Pâncreas/diagnóstico por imagem , Adulto , Aloenxertos/diagnóstico por imagem , Glicemia/metabolismo , Feminino , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/métodos , Masculino , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Transplante Homólogo/métodos
8.
Am J Transplant ; 15(11): 2931-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26108421

RESUMO

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.


Assuntos
Doenças Cardiovasculares/mortalidade , Função Retardada do Enxerto/epidemiologia , Transplante de Rim/métodos , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Fatores Etários , Idoso , Biópsia por Agulha , Estudos de Coortes , Função Retardada do Enxerto/patologia , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Imuno-Histoquímica , Cuidados Intraoperatórios/métodos , Estimativa de Kaplan-Meier , Transplante de Rim/efeitos adversos , Masculino , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Transplantados/estatística & dados numéricos , Resultado do Tratamento , Reino Unido
9.
Clin Transplant ; 29(7): 588-93, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25965009

RESUMO

BACKGROUND: Laparoscopic donor nephrectomy may convert short main arteries into multiple arteries, increasing the technical challenge of implantation. We evaluated our experience to identify factors predictive of multiple arteries after laparoscopic nephrectomy. METHODS: All laparoscopic nephrectomies from the start of our program in November 2002 until June 2013 were studied, and preoperative imaging reviewed for donor artery length and multiplicity together with operative findings. RESULTS: A total of 287 consecutive laparoscopic live donor nephrectomies (64 right and 223 left nephrectomies) were studied. Renal artery length was measured from preoperative donor magnetic resonance or computed tomography angiogram and nephrectomy performed using a laparoscopic stapling device. Nine left kidneys with a single artery (6, 7, 9, 10, 11, 12, 13, 14, and 16 mm in length) and five right kidneys with a single artery (5, 13, 15, 20, and 26 mm) on imaging resulted in multiple renal arteries at implantation. Complex renal vein anatomy was associated with multiple arteries following retrieval. CONCLUSION: A main renal artery length of more than 16 mm on the left and 26 mm on the right is unlikely to result in multiple arteries to implant. The possibility of multiple arteries should be borne in mind when the donor renal artery is short.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim , Laparoscopia/métodos , Doadores Vivos , Nefrectomia/métodos , Artéria Renal/anormalidades , Coleta de Tecidos e Órgãos/métodos , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Artéria Renal/cirurgia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Am J Transplant ; 15(9): 2501-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25932715

RESUMO

We report for the first time the adoptive transfer of donor HLA-specific allosensitization in two recipients following kidney transplantation from a highly sensitized donor. Kidneys from a donation after circulatory death donor were transplanted into two nontransfused, HLA-specific antibody negative males receiving their first transplant. Antibody screening 7 days after transplant showed high level de novo IgG HLA class I- and class II-specific antibodies in both recipients, with largely overlapping antibody profiles but no antibodies to donor HLA. The unusually rapid appearance of de novo alloantibodies in immunosuppressed nonsensitized recipients and absence of donor HLA-specific antibody prompted testing of stored donor serum that revealed high antibody levels with specificities very similar to those seen in both recipients, but in addition the presence of strong antibodies to each recipient HLA. Alloantibody levels gradually declined but were still detectable at 3 months. These findings suggest that alloreactive passenger B cells/plasma cells within the kidneys of highly sensitized donors may give rise to rapid development of posttransplant de novo HLA-specific alloantibodies. While the clinical significance of this phenomenon is uncertain it provides one explanation for the appearance of de novo HLA-specific antibodies directed against third party but not donor HLA.


Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , Doadores de Tecidos , Transplantados , Linfócitos B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
11.
Am J Transplant ; 15(9): 2475-82, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25989187

RESUMO

A significant number of pancreases procured for transplantation are deemed unsuitable due to concerns about graft quality and the associated risk of complications. However, this decision is subjective and some declined grafts may be suitable for transplantation. Ex vivo normothermic perfusion (EVNP) prior to transplantation may allow a more objective assessment of graft quality and reduce discard rates. We report ex vivo normothermic perfusion of human pancreases procured but declined for transplantation, with ABO-compatible warm oxygenated packed red blood cells for 1-2 h. Five declined human pancreases were assessed using this technique after a median cold ischemia time of 13 h 19 min. One pancreas, with cold ischemia over 30 h, did not appear viable and was excluded. In the remaining pancreases, blood flow and pH were maintained throughout perfusion. Insulin secretion was observed in all four pancreases, but was lowest in an older donation after cardiac death pancreas. Amylase levels were highest in a gland with significant fat infiltration. This is the first study to assess the perfusion, injury, as measured by amylase, and exocrine function of human pancreases using EVNP and demonstrates the feasibility of the approach, although further refinements are required.


Assuntos
Tomada de Decisão Clínica , Função Retardada do Enxerto/prevenção & controle , Seleção do Doador , Preservação de Órgãos , Transplante de Pâncreas , Perfusão/métodos , Coleta de Tecidos e Órgãos , Adolescente , Adulto , Amilases/metabolismo , Função Retardada do Enxerto/diagnóstico , Função Retardada do Enxerto/metabolismo , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Temperatura
12.
Am J Transplant ; 15(3): 754-63, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25639995

RESUMO

Histological assessment of baseline chronic kidney injury may discriminate kidneys that are suitable for transplantation, but has not been validated for appraisal of donation after circulatory death (DCD) kidneys. 'Time-zero' biopsies for 371 consecutive, solitary, deceased-donor kidneys transplanted at our center between 2006 and 2010 (65.5% DCD, 34.5% donation after brain death [DBD]) were reviewed and baseline chronic degenerative injury scored using Remuzzi's classification. High scores correlated with donor age and extended criteria donors (42% of donors), but the spectrum of scores was similar for DCD and DBD kidneys. Transplant outcomes for kidneys scoring from 0 to 4 were comparable (1 and 3 year graft survival 95% and 92%), but were much poorer for kidneys scoring ≥5, with 1 year graft survival only 73%, and 12.5% suffering primary nonfunction. Critically, high Remuzzi scores conferred the same survival disadvantage for DCD and DBD kidneys. On multi-variable regression analysis, time-zero biopsy score was the only independent predictor for graft survival, whereas one-year graft estimated glomerular filtration rate (eGFR) correlated with donor age and biopsy score. In conclusion, the relationship between severity of chronic kidney injury and transplant outcome is similar for DCD and DBD kidneys. Kidneys with Remuzzi scores of ≤4 can be implanted singly with acceptable results.


Assuntos
Transplante de Rim , Rim/lesões , Doadores de Tecidos , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
13.
Am J Transplant ; 15(6): 1632-43, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25707303

RESUMO

Early graft loss (EGL) after kidney transplantation is a catastrophic outcome that is assumed to be more likely after the use of kidneys from suboptimal donors. We therefore examined its incidence, risk factors and consequences in our center in relation to different donor types. Of 801 recipients who received a kidney-only transplant from deceased donors, 50 (6.2%) suffered EGL within 30 days of transplantation. Significant risks factors for EGL were donation after circulatory death (DCD) (odds ratio [OR] 2.88; p = 0.006), expanded criteria donor (ECD) transplantation (OR 4.22; p = 0.010), donor age (OR 1.03; p = 0.044) and recipient past history of thrombosis (OR 4.91; p = 0.001). Recipients with EGL had 12.28 times increased risk of death within the first year, but long-term survival was worse for patients remaining on the waiting list. In comparison with patients on the waiting list but not transplanted, and with all patients on the waiting list, the risk of death after EGL decreased to baseline 4 and 23 months after transplantation, respectively. Our findings suggest that DCD and ECD transplantation are significant risk factors for EGL, which is a major risk factor for recipient death. However, long-term mortality is even greater for those remaining on the waiting list.


Assuntos
Cadáver , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim , Doadores de Tecidos , Adulto , Idoso , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Listas de Espera/mortalidade
14.
Bone Marrow Transplant ; 50(4): 540-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25621806

RESUMO

We determined whether assessment of the immunogenicity of individual donor-recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n=171) and 10/10 HLA-A-, -B-, -C-, -DRB1- and -DQB1-matched grafts (n=168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of ⩾grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLA-mismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT.


Assuntos
Bases de Dados Factuais , Doença Enxerto-Hospedeiro , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Adolescente , Adulto , Algoritmos , Aloenxertos , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Antígenos HLA/química , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Incidência , Masculino , Países Baixos , Fatores de Risco
15.
Curr Opin Organ Transplant ; 19(4): 420-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24977436

RESUMO

PURPOSE OF REVIEW: The immunogenic capacity of donor human leukocyte antigen (HLA) to induce humoral immune responses is not an intrinsic property of the mismatched alloantigen but depends on the HLA phenotype of the recipient. In recent years, advances in molecular sequence technology and information from X-ray crystallography have enabled structural comparison of donor and recipient HLA type providing an opportunity for a more rational approach for determining HLA compatibility. In this article, we review studies investigating the molecular basis of antibody-antigen interactions and present computational approaches to determine the complex physiochemical and structural properties of B-cell epitopes. RECENT FINDINGS: The relative immunogenicity of individual HLA mismatches may be predicted from analysis of polymorphic amino acids at continuous and discontinuous HLA sequence positions. The use of alloantigen sequence information alone, however, provides limited insight into key determinants of B-cell epitope immunogenicity, such as the orientation, accessibility and physiochemical properties of amino acid side chains. Advances in computational molecular modelling techniques now enable assessment of HLA-alloantibody interactions at the atomic level. Recent evidence supports a strong link between HLA B-cell epitope surface electrostatic potential and their immunogenicity. SUMMARY: Assessment of the surface electrostatic properties of HLA alloantigens and computational analyses of HLA-alloantibody interactions represent a promising area for future research into the molecular basis of HLA immunogenicity and antigenicity.


Assuntos
Epitopos de Linfócito B/imunologia , Antígenos HLA/imunologia , Formação de Anticorpos/imunologia , Antígenos HLA/química , Antígenos HLA/genética , Humanos , Imunidade Inata , Isoantígenos/imunologia , Eletricidade Estática
17.
Br J Anaesth ; 113(1): 83-90, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24335581

RESUMO

BACKGROUND: The UK has implemented a national strategy for organ donation that includes a centrally coordinated network of specialist nurses in organ donation embedded in all intensive care units and a national organ retrieval service for deceased organ donors. We aimed to determine whether despite the national approach to donation there is significant regional variation in deceased donor kidney donation rates. METHODS: The UK prospective audit of deaths in critical care was analysed for a cohort of patients who died in critical care between April 2010 and December 2011. Multivariate logistic regression was used to identify the factors associated with kidney donation. The logistic regression model was then used to produce risk-adjusted funnel plots describing the regional variation in donation rates. RESULTS: Of the 27 482 patients who died in a critical care setting, 1528 (5.5%) became kidney donors. Factors found to influence donation rates significantly were: type of critical care [e.g. neurointensive vs general intensive care: OR 1.53, 95% confidence interval (CI) 1.34-1.75, P<0.0001], patient ethnicity (e.g. 'Asian' vs 'white': OR 0.17, 95% CI 0.11-0.26, P<0.0001), age (e.g. age >69 vs age 18-39 yr: OR 0.2, 0.15-0.25, P<0.0001), and cause of death [e.g. 'other' (excluding 'stroke' and 'trauma') vs 'trauma': OR 0.04, 95% CI 0.03-0.05, P<0.0001]. Despite correction for these variables, kidney donation rates for the 20 UK kidney donor regions showed marked variation. The overall standardized donation rate ranged from 3.2 to 7.5%. Four regions had donation rates of >2 standard deviations (sd) from the mean (two below and two above). Regional variation was most marked for donation after circulatory death (DCD) kidney donors with 9 of the 20 regions demonstrating donation rates of >2 sd from the mean (5 below and 4 above). CONCLUSIONS: The marked regional variation in kidney donation rates observed in this cohort after adjustment for factors strongly associated with donation rates suggests that there is considerable scope for further increasing kidney donation rates in the UK, particularly DCD.


Assuntos
Transplante de Rim/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Causas de Morte , Estudos de Coortes , Enfermagem de Cuidados Críticos/organização & administração , Etnicidade/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/organização & administração , Pessoa de Meia-Idade , Estudos Prospectivos , Coleta de Tecidos e Órgãos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/normas , Reino Unido/epidemiologia , Adulto Jovem
18.
Rev Sci Instrum ; 84(8): 083908, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24007080

RESUMO

We present design and performance details for a polycapillary-coupled x-ray spectrometer that provides very high collection efficiency at a moderate energy resolution suitable for many studies of nonresonant x-ray emission spectroscopy, especially for samples of heavy elements under high pressures. Using a single Bragg analyzer operating close to backscattering geometry so as to minimize the effect of the weak divergence of the quasicollimated exit beam from the polycapillary optic, this instrument can maintain a typical energy resolution of 5 eV over photon energies from 5 keV to 10 keV. We find dramatically improved count rates as compared to a traditional higher-resolution instrument based on a single spherically bent crystal analyzer.

20.
Curr Opin Organ Transplant ; 18(2): 133-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23425786

RESUMO

PURPOSE: Controlled donation after circulatory death (DCD) donors make an important contribution to organ transplantation but there is considerable scope for further increasing the conversion of potential to actual DCD organ donors. The period between withdrawal of life-supporting treatment and death (the withdrawal period) is a major determinant of whether organ donation proceeds and it is therefore timely to review recent relevant studies in this area. RECENT FINDINGS: The duration and haemodynamic nature of the withdrawal period is extremely variable, and clinical guidelines for management of the potential donor during this period differ widely. Recent evidence suggests that kidneys from DCD donors with a prolonged withdrawal period can be used to increase the number of transplants performed and provide satisfactory graft function, suggesting that it is not the duration but the haemodynamic profile of the donor during this phase that are important. This suggestion questions the relevance of clinical indices predicting death within 1 h of treatment withdrawal. SUMMARY: Future studies should aim to define clinical and physiological variables during the withdrawal period that can be used to maximize well tolerated use of organs from potential DCD donors; these thresholds are likely to differ according to organ type.


Assuntos
Morte , Parada Cardíaca/etiologia , Obtenção de Tecidos e Órgãos , Suspensão de Tratamento , Seleção do Doador , Humanos , Transplante de Órgãos , Fatores de Tempo , Doadores de Tecidos
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