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1.
Occup Med (Lond) ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970463

RESUMO

BACKGROUND: The high prevalence of burnout among Swedish physicians may have several possible effects on individuals and society. However, further investigations of work-related factors associated with the risk of burnout among Swedish physicians are needed. AIMS: We aimed to study the associations between psychosocial work factors, based on the effort-reward imbalance (ERI) model, and the risk of burnout among Swedish physicians. METHODS: A representative sample of 7200 Swedish physicians was invited in 2021. Data were gathered through questionnaires, with a response rate of 41%. Logistic regression models were used to study the associations between exposure to ERI and the risk of burnout. RESULTS: Approximately 62% of Swedish physicians were exposed to a high ERI. Exposure to a high ERI was associated with 11 times increased risk (95% confidence interval 6.5-20.0) of burnout in adjusted models. Large variations in the prevalence of ERI and risk of burnout across sociodemographic and occupational factors were identified, particularly across different clinical specialties. CONCLUSIONS: A majority of Swedish physicians were exposed to high levels of work-related stress, strongly associated with an increased risk of burnout. This population-based cross-sectional study underlines the need to further study variations of work-related stress across clinical specialties and to monitor occupational health among physicians longitudinally.

2.
Occup Med (Lond) ; 73(5): 243-248, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37210591

RESUMO

BACKGROUND: Despite a high prevalence of mental health problems among physicians, the rate of help-seeking behaviour is low. Instead, physicians tend to self-treat. This can have a negative impact on individual physicians and society. AIMS: The aim was to explore the relationship between self-rated depression, the use of psychotropic medication, and the extent of self-treatment across gender and hierarchical position among Swedish physicians. In addition, the aim was to investigate whether social support can buffer against self-treatment. METHODS: This study draws on data from the Longitudinal Occupational Health for Health Care in Sweden 2021 study, comprising a representative sample of physicians. Descriptive statistics and logistic regressions were carried out. RESULTS: The present study showed that approximately 60% of the physicians using narcotic or non-narcotic psychotropic medication were self-prescribing. Male and more senior physicians self-treated to a greater extent. Physicians without depression were self-treating to a greater extent than those with depression. Those who used non-narcotic psychotropic medication intermittently were more likely to self-treat than those who used these medications regularly. The frequency of use was insignificant in relation to self-treatment with narcotic psychotropic medication. No buffering effect from social support at work was found. CONCLUSIONS: Self-treatment was common among physicians in Sweden, particularly among those who reported mild or no symptoms of depression. This may have negative long-term effects on an individual level and for Swedish health care at large.


Assuntos
Saúde Mental , Médicos , Humanos , Masculino , Feminino , Suécia/epidemiologia , Psicotrópicos/uso terapêutico
3.
Trials ; 23(1): 577, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854370

RESUMO

BACKGROUND: Systematic reviews suggest that preschool environmental/organizational changes may be effective in increasing physical activity (PA) levels of preschool children, but evidence is scarce regarding feasible, effective, and equitable interventions that can be scaled up. Specifically, it is essential to understand whether introducing a multicomponent organizational change in terms of policy in the preschool context may be beneficial for children's PA levels and concomitant health outcomes. To bridge this knowledge gap, our main aim is to examine the feasibility and effectiveness of a policy package in increasing PA levels in preschool children, using a large-scale pragmatic cluster-randomized controlled trial. METHODS: This proposed study is a pragmatic cluster-randomized controlled trial with two conditions (intervention and control with a 1:1 ratio) with preschools as clusters and the unit of randomization. We aim to recruit approximately 4000 3-5-year-old children from 90 preschools and retain more than 2800 children from 85 preschools to provide adequate statistical power for the analyses. The intervention to implement is a co-created, multicomponent policy package running for 6 months in preschools randomized to intervention. Change in accelerometer measured PA levels in children between intervention and control from pre- and post-intervention will be the primary outcome of the study, while secondary outcomes include health outcomes such as musculoskeletal fitness, psychosocial functioning, and absence due to illness in children among others. Implementation will be studied carefully using both quantitative (dose, fidelity) and qualitative (interview) methodologies. The change in primary and secondary outcomes, from pre- to post-intervention, will be analyzed with linear mixed-effect models (to allow both fixed and random effects) nested on a preschool level. DISCUSSION: This is a large-scale co-creation project involving the City of Stockholm, childcare stakeholders, preschool staff, and the research group with the potential to influence more than 30,000 preschool children within the Stockholm area. The study will add reliable evidence for the implementation of PA policies at the organizational level of preschools and clarify its potential effect on objectively measured PA and health markers in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT04569578 . Prospectively registered on September 20, 2020.


Assuntos
Exercício Físico , Promoção da Saúde , Criança , Saúde da Criança , Pré-Escolar , Promoção da Saúde/métodos , Humanos , Políticas , Ensaios Clínicos Pragmáticos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Instituições Acadêmicas
4.
Nature ; 600(7890): 621-624, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34937892

RESUMO

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.


Assuntos
Astros Celestes , Atmosfera
5.
Ultrasound Obstet Gynecol ; 57(1): 155-163, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142359

RESUMO

OBJECTIVES: To develop and test the performance of computerized ultrasound image analysis using deep neural networks (DNNs) in discriminating between benign and malignant ovarian tumors and to compare its diagnostic accuracy with that of subjective assessment (SA) by an ultrasound expert. METHODS: We included 3077 (grayscale, n = 1927; power Doppler, n = 1150) ultrasound images from 758 women with ovarian tumors, who were classified prospectively by expert ultrasound examiners according to IOTA (International Ovarian Tumor Analysis) terms and definitions. Histological outcome from surgery (n = 634) or long-term (≥ 3 years) follow-up (n = 124) served as the gold standard. The dataset was split into a training set (n = 508; 314 benign and 194 malignant), a validation set (n = 100; 60 benign and 40 malignant) and a test set (n = 150; 75 benign and 75 malignant). We used transfer learning on three pre-trained DNNs: VGG16, ResNet50 and MobileNet. Each model was trained, and the outputs calibrated, using temperature scaling. An ensemble of the three models was then used to estimate the probability of malignancy based on all images from a given case. The DNN ensemble classified the tumors as benign or malignant (Ovry-Dx1 model); or as benign, inconclusive or malignant (Ovry-Dx2 model). The diagnostic performance of the DNN models, in terms of sensitivity and specificity, was compared to that of SA for classifying ovarian tumors in the test set. RESULTS: At a sensitivity of 96.0%, Ovry-Dx1 had a specificity similar to that of SA (86.7% vs 88.0%; P = 1.0). Ovry-Dx2 had a sensitivity of 97.1% and a specificity of 93.7%, when designating 12.7% of the lesions as inconclusive. By complimenting Ovry-Dx2 with SA in inconclusive cases, the overall sensitivity (96.0%) and specificity (89.3%) were not significantly different from using SA in all cases (P = 1.0). CONCLUSION: Ultrasound image analysis using DNNs can predict ovarian malignancy with a diagnostic accuracy comparable to that of human expert examiners, indicating that these models may have a role in the triage of women with an ovarian tumor. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Análisis de imágenes ecográficas utilizando redes neurales profundas para distinguir entre tumores ováricos benignos y malignos: comparación con la evaluación subjetiva de expertos OBJETIVOS: Desarrollar y probar el desempeño del análisis de imágenes ecográficas computarizadas utilizando redes neurales profundas (RNP) para distinguir entre tumores ováricos benignos y malignos y comparar su precisión en el diagnóstico con la de la evaluación subjetiva (ES) por especialistas expertos en ecografía. MÉTODOS: Se incluyeron 3077 (escala de grises, n=1927; power Doppler, n=1150) imágenes de ultrasonido de 758 mujeres con tumores ováricos, que fueron clasificadas prospectivamente por examinadores especialistas en ecografía, de acuerdo con los términos y definiciones de la IOTA (Análisis Internacional de Tumores Ováricos). El resultado histológico de la cirugía (n=634) o el seguimiento a largo plazo (≥3 años) (n=124) sirvieron como el estándar de referencia. El conjunto de datos se dividió en un subconjunto de formación (n=508; 314 benignos y 194 malignos), un subconjunto de validación (n=100; 60 benignos y 40 malignos) y un subconjunto de pruebas (n=150; 75 benignos y 75 malignos). Se utilizó el aprendizaje de transferencia en tres RNP pre-formadas: VGG16, ResNet50 y MobileNet. Cada modelo fue formado primero mediante escalas de temperatura, al igual que los la calibración de los outputs. A continuación, se utilizó una combinación de los tres modelos para estimar la probabilidad de que el tumor fuera maligno con base en la totalidad de las imágenes de un caso determinado. La combinación de RNP permitió clasificar los tumores como benignos o malignos (modelo Ovry-Dx1); o como benignos, no concluyentes o malignos (modelo Ovry-Dx2). Se comparó el desempeño para el diagnóstico de los modelos de RNP, en términos de sensibilidad y de especificidad, con el de la ES para la clasificación de los tumores ováricos en el subconjunto de formación. RESULTADOS: Con una sensibilidad del 96,0%, Ovry-Dx1 tuvo una especificidad similar a la de la ES (86,7% frente a 88,0%; P=1,0). Ovry-Dx2 tuvo una sensibilidad del 97,1% y una especificidad del 93,7%, y designaron un 12,7% de las lesiones como no concluyentes. Cuando se complementó Ovry-Dx2 con ES en los casos no concluyentes, la sensibilidad general (96,0%) y la especificidad (89,3%) no fueron significativamente diferentes de la utilización de ES en todos los casos (P=1,0). CONCLUSIÓN: El análisis de imágenes ecográficas mediante RNP puede predecir el cáncer de ovario con una precisión en el diagnóstico igual a la de los especialistas expertos humanos, lo que indica que estos modelos pueden jugar un papel en el triaje de mujeres con un tumor de ovario. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Doenças dos Anexos/diagnóstico , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Ovarianas/diagnóstico , Doenças dos Anexos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Ovarianas/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Ultrassonografia Doppler
6.
Sci Rep ; 10(1): 18813, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33110241

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

7.
Sci Rep ; 9(1): 8981, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222088

RESUMO

Food-provisioning of wildlife can facilitate reliable up-close encounters desirable by tourists and, consequently, tour operators. Food-provisioning can alter the natural behavior of an animal, encouraging adverse behavior (e.g. begging for food handouts), and affect the reproductive success and the viability of a population. Studies linking food-provisioning to reproductive success are limited due to the lack of long-term datasets available, especially for long-lived species such as marine mammals. In Bunbury, Western Australia, a state-licensed food-provisioning program offers fish handouts to a limited number of free-ranging bottlenose dolphins (Tursiops aduncus). Coupled with long-term historical data, this small (<200 individuals), resident dolphin population has been extensively studied for over ten years, offering an opportunity to examine the effect of food-provisioning on the reproductive success of females (ntotal = 63; nprovisioned females = 8). Female reproductive success was estimated as the number of weaned calves produced per reproductive years and calf survival at year one and three years old was investigated. The mean reproductive success of provisioned and non-provisioned females was compared using Bayes factor. We also used generalized linear models (GLMs) to examine female reproductive success in relation to the occurrence of food-provisioning, begging behavior and location (within the study area). Furthermore, we examined the influence of these variables and birth order and climatic fluctuations (e.g. El Niño Southern Oscillation) on calf survival. Bayes factor analyses (Bayes factor = 6.12) and results from the best fitting GLMs showed that female reproductive success and calf survival were negatively influenced by food-provisioning. The negative effects of food-provisioning, although only affecting a small proportion of the adult females' population (13.2%), are of concern, especially given previous work showing that this population is declining.


Assuntos
Ração Animal , Animais Selvagens , Golfinho Nariz-de-Garrafa , Reprodução , Animais , Feminino , Humanos , Atividades de Lazer , Masculino , Fatores Sexuais , Taxa de Sobrevida , Austrália Ocidental
8.
Tissue Antigens ; 79(4): 263-71, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22320834

RESUMO

The frequency of the killer-cell immunoglobulin-like receptor (KIR) genes and transmembrane alleles of KIR2DL4 were studied in coastal (Mugil community) and inland (Ilaita community) communities in Papua New Guinea. Linkage disequilibria between KIR genes and between alleles of KIR2DL4 and the KIR genes were similar to those found in other populations suggesting conservation of the usual gene order in Papua New Guinean haplotypes. Significant differences in the frequency of KIR genes were found between the two populations despite being separated by only 300 km. Examples of individuals who lacked the KIR2DL4 gene and others whose KIR2DL4 allele appeared to have 11 adenines in the polyadenine tract in exon 6 were identified. A relatively low frequency of the KIR A haplotype was found in both populations and particularly in the inland community. The KIR gene frequencies were consistent with the inland Ilaita community being closely related to Australian Aborigines and southern Indians, whereas the KIR gene frequencies of the coastal Mugil community appeared to have been influenced either by recent or ancient admixture from populations with a higher frequency of the KIR A haplotype.


Assuntos
Frequência do Gene , Genética Populacional , Receptores KIR/genética , Adolescente , Criança , Pré-Escolar , Feminino , Ligação Genética , Genótipo , Humanos , Lactente , Masculino , Papua Nova Guiné , Reação em Cadeia da Polimerase , Receptores KIR2DL4/genética
9.
Am J Transplant ; 11(2): 272-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21070601

RESUMO

We developed and tested a new computer program to match maximal sets of incompatible live donor/recipient pairs from a national paired kidney donation (PKD) registry. Data of 32 incompatible pairs included ABO and 4 digit-high-resolution donor and recipient HLA antigens and recipient's HLA antibodies. Three test runs were compared, in which donors were excluded from matching to recipients with either donor-specific antibodies (DSA) >8000MFI (mean fluorescent intensity) at low-resolution (Run 1) or >8000MFI at high-resolution (Run 2) or >2000MFI and high-resolution (Run 3). Run 1 identified 22 703 possible combinations, with 20 pairs in the top ranked, Run 2 identified 24 113 combinations, with 19 pairs in the top ranked and Run 3 identified 8843 combinations, with 17 pairs in the top ranked. Review of DSA in Run 1 revealed that six recipients had DSA 2000-8000MFI causing a possible positive crossmatch resulting in breakdown of two 3-way and three 2-way chains. In Run 2, four recipients had DSA 2000-8000MFI, also potentially causing breakdown of three 2-way chains. The more prudent approach of excluding from matching recipients with DSA with >2000MFI reduces the probability of matched pairs having a positive crossmatch without significantly decreasing the number of possible transplants.


Assuntos
Doação Dirigida de Tecido/estatística & dados numéricos , Teste de Histocompatibilidade/métodos , Teste de Histocompatibilidade/estatística & dados numéricos , Transplante de Rim/imunologia , Transplante de Rim/métodos , Interface Usuário-Computador , Algoritmos , Humanos , Doadores Vivos/estatística & dados numéricos , Software , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Austrália Ocidental
10.
J Anim Sci ; 88(11): 3522-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20656975

RESUMO

Quantitative trait loci for milk production traits in Danish Jersey cattle were mapped by a genome-wide association analysis using a mixed model. The analysis incorporated 1,039 bulls and 33,090 SNP and resulted in 98 detected combinations of QTL and traits on 27 BTA. These QTL comprised 30 for milk index, 50 for fat index, and 18 for protein index. The evidence presents 33 genome-wide QTL on 14 BTA. Of these, 7 had effects on milk index, 21 on fat index, and 5 on protein index. Among the genome-wide QTL, 26 have been previously reported, 2 on BTA4 and BTA5 were new for milk index, and 5 on BTA4, BTA5, BTA13, BTA20, and BTA29 were new QTL for fat index. We found 7 pleiotropic or very closely linked QTL. Most of the QTL were associated with polymorphisms within narrow regions and several may represent the effects of polymorphisms of genes: DGAT1, casein, ARFGAP3, CYP11B1, and CDC-like kinase 4. By a chromosome-wide threshold, 65 additional QTL were detected. Many of them are likely to represent QTL. The results are interesting from a breeding perspective and contribute to the search for the genes causing the polymorphisms important for milk production traits.


Assuntos
Lactação/genética , Polimorfismo de Nucleotídeo Único , Animais , Bovinos , Mapeamento Cromossômico/veterinária , Feminino , Marcadores Genéticos , Genoma , Lactação/fisiologia , Masculino , Locos de Características Quantitativas
11.
Clin Exp Immunol ; 159(1): 65-72, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19860744

RESUMO

Low-level alloreactivity between mother and fetus may provide stimulation for fetal T helper type 1 (Th1) cell immune maturation. This study explored the effects of human leucocyte antigen (HLA) mismatch on materno-fetal interactions detected as cytokine responses and lymphoproliferation in mixed lymphocyte reactions, and whether this was altered in allergic women (n = 62) who have a Th2 propensity compared with non-allergic women (n = 65). HLA-DRbeta1 mismatch was associated with significantly increased Th1 interferon (IFN)-gamma, Th2 interleukin (IL)-13 and lymphoproliferative responses by both mothers and fetuses. Allergic women showed significantly lower IFN-gamma Th1 production in response to HLA-DRbeta1 mismatch. The infants of these women also showed significantly lower IL-10 and lower IFN-gamma production relative to IL-13. Both HLA-DRbeta1 mismatch and maternal allergy had significant independent effects on maternal IFN-gamma Th1 responses. Maternal allergy modifies HLA-mediated alloreactivity between the mother and the fetus, reducing Th1 activation. This may affect the cytokine milieu at the materno-fetal interface and could be implicated in the attenuated Th1 responses observed commonly in infants of atopic mothers.


Assuntos
Feto/imunologia , Antígenos HLA/imunologia , Hipersensibilidade/imunologia , Isoantígenos/imunologia , Células Th1/imunologia , Adolescente , Adulto , Proliferação de Células , Feminino , Número de Gestações/imunologia , Antígenos HLA/genética , Antígenos HLA-C/genética , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Teste de Histocompatibilidade , Humanos , Hipersensibilidade/genética , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-6/metabolismo , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/imunologia , Teste de Cultura Mista de Linfócitos , Gravidez , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Adulto Jovem
12.
Mol Hum Reprod ; 15(8): 489-97, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19509110

RESUMO

Natural killer (NK) cells are the predominant leukocyte in first trimester decidua and play a role in vascular remodelling through interferon gamma (IFNgamma) secretion. Membrane expression of the killer immunoglobulin-like receptor (KIR) KIR2DL4 on peripheral blood NK (pNK) cells is controlled by the 9A/10A transmembrane genetic polymorphism. On peripheral NK cells (pNK), KIR2DL4 can only be detected on the membrane of cells from individuals with at least one copy of the 10A allele and ligation of KIR2DL4 results in IFNgamma secretion. In this study, we assessed KIR2DL4 expression and IFNgamma secretion as a result of KIR2DL4 ligation, by decidual NK (dNK) cells. The 9A/10A transmembrane polymorphism was shown to control KIR2DL4 expression by dNK, as previously shown for pNK cells. Freshly isolated dNK cells from subjects with at least one 10A allele expressed KIR2DL4 whereas those from 9A homozygous subjects did not. Although freshly isolated dNK did not secrete IFNgamma in response to KIR2DL4 ligation regardless of KIR2DL4 genotype, activation by in vitro culture with IL-2 enabled dNK cells from individuals with at least one 10A allele, but not those without a 10A allele, to secrete IFNgamma in response to KIR2DL4 ligation. This study confirms that expression of KIR2DL4 by dNK is dependent on the 9A/10A polymorphism and that this polymorphism influences IFNgamma secretion by dNK cells.


Assuntos
Decídua/citologia , Interferon gama/metabolismo , Células Matadoras Naturais/metabolismo , Receptores KIR2DL4/genética , Receptores KIR2DL4/metabolismo , Anticorpos Monoclonais/metabolismo , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Genótipo , Humanos , Gravidez
13.
J Neurol Neurosurg Psychiatry ; 79(9): 1056-60, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18258695

RESUMO

BACKGROUND AND AIMS: There have been few studies of the variability in the clinical phenotype in sporadic inclusion body myositis (sIBM) and it is not known whether the human leucocyte antigen (HLA) haplotype influences the phenotype and course of the disease. We studied a large cohort of patients with sIBM in order to determine the degree of phenotypic variability and different modes of presentation, as well as the influence of HLA haplotypes. METHOD: A cross-sectional study of 57 biopsy-proven sIBM cases from three Australian centres was performed. Patients were interviewed and examined by a single investigator, and had HLA typing and autoantibody studies. RESULTS: Although the initial symptoms in the majority of cases were attributable to quadriceps weakness (79%), a proportion of patients presented due to finger weakness (12%), foot drop (7%) or dysphagia (1.8%). Although the majority had the classic combination of quadriceps and forearm muscle involvement, some patients had predominantly forearm weakness with sparing of the quadriceps, or severe involvement of the anterior tibial muscles. Asymmetrical involvement was common (82%), particularly of the forearm muscles, with the non-dominant side being more severely affected in most cases. Carriage of the HLA-DRB1*0301 (DR3) allele was associated with lower quadriceps muscle strength and a more rapid decline in strength. CONCLUSIONS: The findings emphasise the variability in the mode of presentation, patterns of muscle involvement and clinical course of sIBM in this population, and indicate that the HLA-DRB1*0301 (DR3) allele may influence the rate of progression as well as susceptibility to the disease.


Assuntos
Variação Antigênica/genética , Antígeno HLA-DR3/genética , Antígeno HLA-DR3/imunologia , Miosite de Corpos de Inclusão/genética , Fenótipo , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Austrália/epidemiologia , Autoanticorpos/imunologia , Estudos Transversais , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Demografia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fadiga Muscular , Debilidade Muscular/diagnóstico , Debilidade Muscular/epidemiologia , Debilidade Muscular/fisiopatologia , Miosite de Corpos de Inclusão/epidemiologia , Miosite de Corpos de Inclusão/fisiopatologia , Prevalência , Músculo Quadríceps/fisiopatologia
14.
Tissue Antigens ; 69 Suppl 1: 56-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17445165

RESUMO

The Royal Perth Hospital laboratory has been using sequencing-based typing for all HLA loci since 2002. In the period to October 2005, approximately 12,000 HLA A and HLA B, 5000 HLA C and DQB1, and 17,000 DRB1 requests have been processed. Twenty nine novel alleles have been identified in that time. These comprise 10 HLA-A (including one null allele), five HLA-B, six HLA-C, six DRB1 (including a null allele), and one DQB1 novel allele. (At the time of identifying the DRB1 null allele, there were no other reported examples.) In addition, we have seen one example of a blast-specific HLA-A null allele. One HLA-A allele (HLA-A*0264) and one HLA-B allele (HLA-B*400104) were subsequently identified in other laboratories and submitted to the international ImMunoGeneTics project (IMGT) database.


Assuntos
Antígenos HLA/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Alelos , Sequência Conservada , Haplótipos/genética , Haplótipos/imunologia , Humanos , Dados de Sequência Molecular
15.
Tissue Antigens ; 69 Suppl 1: 58-60, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17445166

RESUMO

Since the introduction of DNA-based human leukocyte antigen (HLA) typing a number of discrepancies with serological typing have been documented. At the time of submission of this abstract (July 2005 ImMunoGeneTics project (IMGT) project database release) 42 HLA class I and II null alleles had been described characterised by a lack of expression of cell surface antigen. These null alleles can be accounted for by a number of demonstrated molecular mechanisms including insertion, deletion and point mutation and may lead to a nonsense codon, splicing defect or premature stop codon.


Assuntos
Alelos , Doença Celíaca/genética , Antígenos HLA-DR/genética , Sequência de Bases , Doença Celíaca/imunologia , Cadeias HLA-DRB1 , Humanos , Dados de Sequência Molecular , Homologia de Sequência do Ácido Nucleico
16.
Tissue Antigens ; 69 Suppl 1: 85-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17445174

RESUMO

During the last few years many laboratories have developed a keen interest in detecting killer immunoglobulin-like receptor (KIR) receptor genes in various populations, diseases and in stem cell transplantation. At the 14th International Histocompatibility Workshop held in Melbourne in December 2006, many of these laboratories presented their findings at a special session. To introduce this work, we provide an introduction to KIR receptors and an outline of previous applications of KIR receptor typing prior to the Workshop.


Assuntos
Antígenos HLA/genética , Imunogenética , Células Matadoras Naturais/imunologia , Receptores Imunológicos/genética , Humanos , Receptores Imunológicos/metabolismo , Receptores KIR
17.
Tissue Antigens ; 69 Suppl 1: 174-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17445195

RESUMO

An international collaborative study of 45 transplant centers was undertaken at the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop to see if HLA antibodies detected posttransplant are predictive of chronic graft failure. With the newly developed assay, MICA (major histocompatibility complex class I-related chain A) antibodies were also measured and their effect analyzed. Total of 5219 sera from patients who were more than 6 months posttransplant with functioning graft were tested for HLA antibodies by enzyme-linked immunosorbent assay, flow cytometry, or Luminex. HLA antibodies were found in 27.2% of kidney patients, 23.6% in the liver, 52.7% in the heart, and 21.7% in the lung. The method of antibody testing did not have a marked influence on the frequency of antibodies detected. MICA antibodies were detected in 15% of kidney patients, 30% of heart patients, and 31% of liver patients. Among 948 kidney patients who had HLA antibodies, 7.3% had rejected their graft within 1 year of testing, compared with 1.7% in 2615 patients without HLA antibodies (P= 0.8 x 10(-17)). Death occurred in 1.4% of total kidney patients and did not correlate to the presence of antibodies. We conclude that patients with posttransplant HLA antibodies indeed have a higher rate of chronic graft failure and that posttransplant antibodies are predictive of chronic rejection.


Assuntos
Rejeição de Enxerto/etiologia , Antígenos HLA/imunologia , Transplante de Coração/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Imunogenética , Transplante de Rim/imunologia , Imunologia de Transplantes , Doença Crônica , Sobrevivência de Enxerto , Transplante de Coração/efeitos adversos , Teste de Histocompatibilidade , Humanos , Transplante de Rim/efeitos adversos
18.
Am J Transplant ; 7(4): 847-56, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17391128

RESUMO

HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p < 0.0001) when detected by ELISA, and a HR of 6.0 (p < 0.0001) when detected by Luminex. A high post-transplant sCD30 level >or=100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p < 0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.


Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA-D/imunologia , Isoanticorpos/sangue , Antígeno Ki-1/sangue , Transplante de Rim/imunologia , Adolescente , Adulto , Antígenos CD/sangue , Feminino , Seguimentos , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
19.
Clin Transpl ; : 255-60, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18642456

RESUMO

The three-year follow-up of 4,144 patients of the 14th International Workshop Prospective Chronic Rejection study has reinforced the evidence that post-transplant HLA antibodies are predictive of long-term graft loss. Three years after a single testing for HLA antibodies, 10% of kidney recipients who were antibody-positive had lost their grafts, in contrast to only 5% of antibody-negative patients (p<0.0001). The adverse effect of post-transplant antibodies on graft survival was also observed in lung, heart, and liver transplants. Donor-specific antibodies and 'strong' non-DSA had stronger association with graft loss than 'moderate' non-DSA. Periodic antibody monitoring, combined with specificity and strength analysis, would help in the early identification of allograft recipients who are at high risk of graft failure.


Assuntos
Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade , Transplante de Órgãos/estatística & dados numéricos , Doença Crônica , Educação , Seguimentos , Antígenos HLA/imunologia , Transplante de Coração/imunologia , Transplante de Coração/estatística & dados numéricos , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Estimativa de Kaplan-Meier , Transplante de Rim/imunologia , Transplante de Rim/estatística & dados numéricos , Transplante de Pulmão/imunologia , Transplante de Pulmão/estatística & dados numéricos , Estudos Prospectivos
20.
Hum Immunol ; 67(3): 238-46, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16698448

RESUMO

Genetic testing of the MHC is required for selection of donors for bone marrow transplantation. The outcome of related bone marrow transplantation is usually superior to that of unrelated bone marrow transplantation. This may be the result of inaccurate or incomplete genetic testing employed for selection of donor for transplantation. Based on MHC haplotype matching, MHC block matching has been developed for selection of potential unrelated donor. Block matching has been shown previously to improve outcome when added to the conventional method of human leukocyte antigen (HLA) typing for selection of donors. In this study, we have retrospectively analyzed 44 donor recipient pairs from the Australian Bone Marrow Donor Registry Repository with respect to matching of HLA-B and HLA-Cw by sequence-based typing and MICA and MICB by polymerase chain reaction-sequence specific primer and MHC beta block matching and correlated these results with survival. Beta block matching was correlated with MIC matching (p < 0.005) and with HLA-B and HLA-Cw matching. Patients who were HLA-B and -Cw matched had significantly improved survival when they were additionally matched for MHC beta block (p(c) = 0.04) or MIC (p(c) = 0.05).


Assuntos
Transplante de Medula Óssea/imunologia , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Adolescente , Adulto , Transplante de Medula Óssea/mortalidade , Criança , Seleção do Doador , Feminino , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Tolerância ao Transplante
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