Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.638
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
Nature ; 555(7695): 237-241, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29516998

RESUMO

Laboratory experiments and seismology data have created a clear theoretical picture of the most abundant minerals that comprise the deeper parts of the Earth's mantle. Discoveries of some of these minerals in 'super-deep' diamonds-formed between two hundred and about one thousand kilometres into the lower mantle-have confirmed part of this picture. A notable exception is the high-pressure perovskite-structured polymorph of calcium silicate (CaSiO3). This mineral-expected to be the fourth most abundant in the Earth-has not previously been found in nature. Being the dominant host for calcium and, owing to its accommodating crystal structure, the major sink for heat-producing elements (potassium, uranium and thorium) in the transition zone and lower mantle, it is critical to establish its presence. Here we report the discovery of the perovskite-structured polymorph of CaSiO3 in a diamond from South African Cullinan kimberlite. The mineral is intergrown with about six per cent calcium titanate (CaTiO3). The titanium-rich composition of this inclusion indicates a bulk composition consistent with derivation from basaltic oceanic crust subducted to pressures equivalent to those present at the depths of the uppermost lower mantle. The relatively 'heavy' carbon isotopic composition of the surrounding diamond, together with the pristine high-pressure CaSiO3 structure, provides evidence for the recycling of oceanic crust and surficial carbon to lower-mantle depths.

2.
Anal Bioanal Chem ; 415(22): 5403-5420, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37452840

RESUMO

Synthetic cathinones, one of the most prevalent categories of new psychoactive substances, have been posing a serious threat to public health. Methylmethcathinones (MMCs), notably 3-MMC, have seen an alarming increase in their use in the last decade. The metabolism and toxicology of a large majority of synthetic cathinones, including 3-MMC and 2-MMC, remain unknown. Traditionally, male-derived liver materials have been used as in vitro metabolic incubations to investigate the metabolism of xenobiotics, including MMCs. Therefore, little is known about the metabolism in female-derived in vitro models and the potential sex-specific differences in biotransformation. In this study, the metabolism of 2-MMC, 3-MMC, and 4-MMC was investigated using female rat and human liver microsomal incubations, as well as male rat and human liver microsomal incubations. A total of 25 phase I metabolites of MMCs were detected and tentatively identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Seven sex-specific metabolites were detected exclusively using pooled male rat liver microsomal incubations. In addition, the metabolites generated from the sex-dependent in vitro metabolic incubations that were present in both male and female rat liver microsomal incubations showed differences in relative abundance. Yet, neither sex-specific metabolites nor significant differences in relative abundance were observed from pooled human liver microsomal incubations. This is the first study to report the phase I metabolic pathways of MMCs using in vitro metabolic incubations for both male and female liver microsomes, and the relative abundance of the metabolites observed from each sex.


Assuntos
Alcaloides , Espectrometria de Massas em Tandem , Ratos , Masculino , Humanos , Feminino , Animais , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Alcaloides/análise , Fígado/química , Microssomos Hepáticos/metabolismo
3.
Clin Radiol ; 78(5): 333-339, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36710122

RESUMO

The aim of this review is to discuss end-stage renal disease (ESRD) and renal transplant complications and present the nuclear medicine imaging findings. The conditions discussed are renal osteodystrophy, metastatic calcification, and renal transplant complications, such as vascular occlusion and acute tubular necrosis. A total of eight nuclear medicine imaging scintigraphy primarily of bone and renal scintigraphy were selected and the imaging features of the complications are discussed. This article highlights the role of nuclear medicine imaging in diagnosis, quantitative and qualitative assessment of renal function, and monitoring of complications associated with ESRD and renal transplant.


Assuntos
Falência Renal Crônica , Transplante de Rim , Cintilografia , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-37812319

RESUMO

PURPOSE: The use of angiography in postmortem CT angiography (PMCTA) has several advantages. In adults, femoral vascular access is well established. Due to the small and specific anatomy in fetuses and infants, the technique has to be adapted, especially regarding the vascular access. The aim of this study was to evaluate vascular access for pediatric PMCTA (pedPMCTA). MATERIALS AND METHODS: Ten pedPMCTAs were performed in stillbirths, babies, and one toddler. A femoral approach by cannulation of the femoral artery and vein, an umbilical approach by cannulation of the umbilical vessels, and an intraosseous approach by an intraosseous needle were evaluated by handling and resulting imaging. RESULTS: The insertion of a cannula with a size of 18-20 G in the femoral vessels was possible in babies. An umbilical access with peripheral venous cannulas with a size of 14-20 G was feasible in stillbirths and newborns. An intraosseous access is advisable as equal alternative to umbilical and in cases where a femoral access is not possible. The most significant problem with the vascular access is the extravasation of contrast media, but this can be reduced significantly with practice. CONCLUSION: When performing pedPMCTA, an umbilical vascular access is recommended if an umbilical cord with open vessels is still present. Otherwise, a bone marrow access should be preferred in the presence of an arteriovenous shunt or if only the venous system needs to be shown. If that is not the case, the femoral access with the possibility to separate venous and arterial scan should be used.

5.
BJOG ; 129(2): 256-266, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34735736

RESUMO

BACKGROUND: Pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, but little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. METHODS: We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT-qPCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. FINDINGS: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co-express the two proteins across the second trimester or at term. INTERPRETATION: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. TWEETABLE ABSTRACT: This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS-CoV-2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19 , Perfilação da Expressão Gênica , Placenta/metabolismo , Serina Endopeptidases/genética , Adulto , COVID-19/epidemiologia , COVID-19/genética , COVID-19/transmissão , Bases de Dados de Ácidos Nucleicos , Suscetibilidade a Doenças/metabolismo , Feminino , Pesquisa Fetal , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Testes Genéticos/métodos , Idade Gestacional , Humanos , Imuno-Histoquímica , Transmissão Vertical de Doenças Infecciosas , Gravidez , Fatores de Proteção , Ribonucleoproteínas Citoplasmáticas Pequenas/análise , SARS-CoV-2/fisiologia
6.
J Dairy Sci ; 105(8): 7036-7046, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35787326

RESUMO

Mitochondria are central to metabolism and are the primary energy producers for all biosynthesis, including lactation. The objectives of this study were to determine if high- and low-producing dairy cows exhibit differences in peripheral blood mononuclear cell mitochondrial enzyme activities of citrate synthase, complex I, complex IV, and complex V during early lactation and, thus, to determine whether those differences were related to differences in lactation performance in the dairy cow. Fifty-six Holstein cows were assigned to 1 of 4 groups: (1) primiparous high, (2) primiparous low, (3) multiparous high, or (4) multiparous low. Primiparous and multiparous cows were analyzed separately. Then, cows were divided into high or low production groups for each production parameter [peak milk, average milk, energy-corrected milk (ECM), fat-corrected milk (FCM), milk lactose, milk fat, milk protein, total solids (TS), solids-not-fat, feed efficiency, and somatic cell count (SCC)]. For all data analysis, production parameters are expressed as yields (kg/d) and SCC (103 cells/mL). High and low production groups were defined by their respective mean production parameters for the 56 cows, with below average cows defined as low and above average cows defined as high. Whole blood samples were collected at one time point, approximately 70 d in milk at 0800 h, and processed for crude mitochondrial extracts from peripheral blood mononuclear cells to determine the activity rates of mitochondrial enzymes. Milk samples were collected 9 times (3 d, 3 times per d) during the week of blood collection and analyzed for major components (fat, protein, lactose, TS, and SCC). Multiparous cows had lower citrate synthase activity than primiparous cows across all production parameters. High-producing cows had greater complex I activity for peak milk, milk yield, ECM, FCM, milk fat, TS, and feed efficiency, and greater complex V activity for ECM, FCM, milk lactose, milk fat, and TS across parities. These findings imply that the most influential respiratory chain enzymes on the level of milk production are those responsible for electron transport chain initialization and ATP production.


Assuntos
Lactose , Leucócitos Mononucleares , Animais , Bovinos , Citrato (si)-Sintase , Dieta/veterinária , Feminino , Lactação , Mitocôndrias , Paridade , Gravidez
7.
Pediatr Surg Int ; 37(9): 1281-1286, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34235545

RESUMO

INTRODUCTION: The aetiology and management of ovarian pathology in children differs between antenatal and postnatal lesions. However, all lesions may present acutely due to adnexal torsion. In this setting, opportunities to preserve fertility with ovary-sparing surgery (OSS) may be missed. Some studies suggest that pediatric and adolescent gynaecology (PAG) input in care is associated with OSS. METHODS: A retrospective cohort study of children undergoing surgery for ovarian pathology at a tertiary pediatric surgery centre over an 8-year period (2011-2018). Patient factors, lesion characteristics and PAG involvement were examined for association with OSS using multivariate logistic regression. RESULTS: Thirty-five patients with ovarian pathology managed surgically were included. Ten were infants with lesions detected antenatally; all were managed by pediatric surgeons (PS) alone at median age 2 weeks (1 day-25 weeks). Twenty-five patients presented postnatally at median age 11 (0.75-15) years. In total, there were 16 cases of adnexal torsion, each managed primarily by PS. Twelve underwent oophorectomy and six (50%) of these cases had viable ovarian tissue on histology. Furthermore, two infants with large simple cysts were similarly managed by unnecessary oophorectomy based on histology. Overall rate of OSS was 46% and PAG involvement was the only factor associated with ovarian salvage. CONCLUSION: Differences in surgical management between PAGs and PS may be attributable to the different patient populations they serve. We recommend improving the knowledge of PS trainees in OSS approaches for adnexal torsion and large benign lesions.


Assuntos
Cistos Ovarianos , Neoplasias Ovarianas , Adolescente , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Cistos Ovarianos/cirurgia , Ovariectomia , Gravidez , Estudos Retrospectivos , Anormalidade Torcional
8.
Br J Surg ; 107(9): 1199-1210, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32304225

RESUMO

BACKGROUND: High-output enterostomies and enteroatmospheric fistulas are common causes of intestinal failure, and may necessitate parenteral nutrition and prolonged hospital stay. Reinfusing lost chyme into the distal gut is known to be beneficial, but implementation has been limited because manual reinfusion is unpleasant and labour-intensive, and no devices are available. A new device is presented for reinfusing chyme easily and efficiently, with first-in-human data. METHODS: The device comprises a compact centrifugal pump that fits inside a standard stoma appliance. The pump is connected to an intestinal feeding tube inserted into the distal intestinal limb. The pump is activated across the appliance by magnetic coupling to a hand-held driver unit, effecting intermittent bolus reinfusion while avoiding effluent contact. Safety, technical and clinical factors were evaluated. RESULTS: Following microbiological safety testing, the device was evaluated in ten patients (median duration of installation 39·5 days; total 740 days). Indications included remediation of high-output losses (8 patients), dependency on parenteral nutrition (5), and gut rehabilitation before surgery (10). Reinfusion was well tolerated with use of regular boluses of approximately 200 ml, and no device-related serious adverse events occurred. Clinical benefits included resumption of oral diet, cessation of parenteral nutrition (4 of 5 patients), correction of electrolytes and liver enzymes, and hospital discharge (6 of 10). Of seven patients with intestinal continuity restored, one experienced postoperative ileus. CONCLUSION: A novel chyme reinfusion device was developed and found to be safe, demonstrating potential benefits in remediating high-output losses, improving fluid and electrolyte balance, weaning off parenteral nutrition and improving surgical recovery. Pivotal trials and regulatory approvals are now in process.


ANTECEDENTES: Las ostomías y las fístulas entero-atmosféricas de alto débito son causas frecuentes de insuficiencia intestinal y pueden precisar nutrición parenteral (NP) y una hospitalización prolongada. Se sabe que la reinfusión del quimo perdido en el intestino distal es beneficiosa, pero su práctica se ha visto limitada porque la reinfusión manual es desagradable, laboriosa y no hay dispositivos disponibles. Se presenta un nuevo dispositivo para reinfundir el quimo de forma fácil y eficiente, junto con los primeros datos en humanos. MÉTODOS: El dispositivo constaba de una bomba centrífuga compacta que cabe dentro de una bolsa de ostomía estándar. Esta bomba iba conectada a una sonda intestinal colocada en el intestino distal. La bomba se activa manualmente mediante el acoplamiento magnético de una manivela, que evita el contacto con el efluente y permite efectuar la reinfusión de bolos discontinuos. Se evaluaron factores de seguridad, técnicos y clínicos. RESULTADOS: Después de las pruebas de seguridad microbiológica, se evaluó el dispositivo en 10 pacientes (mediana de tiempo de funcionamiento 39,5 días; total 740 días). Las indicaciones abarcaron la paliación de pérdidas cuantiosas (n = 8), la dependencia de NP (n = 5) y la rehabilitación intestinal antes de la cirugía (n = 10). La reinfusión se toleró bien utilizando bolos repetidos de ~200 ml, y no hubo efectos adversos graves relacionados con el dispositivo. Los beneficios clínicos incluyeron la reanudación de la dieta oral, el cese de la NP (4/5 pacientes), la corrección de trastornos electrolitos y de las enzimas hepáticas y el alta hospitalaria (6/10). De los 7 pacientes en los que se reconstruyó el tránsito digestivo, uno experimentó un íleo postoperatorio. CONCLUSIÓN: Se ha desarrollado un nuevo dispositivo de reinfusión de quimo que ha demostrado su seguridad y beneficios potenciales para paliar pérdidas cuantiosas, restaurar el equilibrio hidroelectrolítico, retirar la NP y mejorar la recuperación quirúrgica. Están en marcha los ensayos clínicos pivotales y el proceso para obtener los permisos reglamentarios.


Assuntos
Fístula Gástrica/cirurgia , Conteúdo Gastrointestinal , Bombas de Infusão , Fístula Intestinal/cirurgia , Estomas Cirúrgicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Diabet Med ; 37(2): 256-266, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31365765

RESUMO

AIMS: Both fasting (FPG) and postprandial plasma glucose (PPG) contribute to HbA1c levels. We investigated the relationship between achievement of American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) recommended FPG and/or PPG targets and glycaemic efficacy outcomes in two trials. METHODS: In this post hoc analysis, data from participants with Type 2 diabetes in the phase 3 LixiLan-O (NCT02058147) and LixiLan-L (NCT02058160) trials were evaluated to compare the relationship between achievement of society-recommended FPG and/or PPG targets and efficacy (HbA1c change, HbA1c goal attainment, weight change) and safety outcomes in the treatment groups. RESULTS: Across treatment arms, iGlarLixi achieved the highest proportion of participants meeting both ADA- and AACE-recommended FPG and PPG targets at study end in both trials. A higher proportion of participants in the iGlarLixi (fixed-ratio combination of insulin glargine and lixisenatide) vs. insulin glargine alone or lixisenatide alone treatment arms achieved HbA1c goals (P < 0.001 for overall comparisons), irrespective of ADA- or AACE-defined targets. Hypoglycaemia rates [any, documented symptomatic (plasma glucose ≤ 3.9 mmol/l), and clinically important (plasma glucose < 3.0 mmol/l)] were low across all groups. Participants treated with iGlarLixi tended to show weight loss or less weight gain compared with participants receiving insulin glargine alone. No differences were observed in average daily basal insulin dose at week 30 between the two treatment arms or across the different FPG and PPG target groups. CONCLUSION: Insulin glargine and lixisenatide as a fixed-ratio combination resulted in more participants reaching both FPG and PPG targets, leading to better HbA1c target attainment.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Peptídeos/uso terapêutico , Período Pós-Prandial , Idoso , Diabetes Mellitus Tipo 2/metabolismo , Combinação de Medicamentos , Feminino , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
Lupus ; 29(5): 474-481, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233733

RESUMO

BACKGROUND: Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15-20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. METHODS: Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years) and adolescent (14-18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. RESULTS: A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4-20] vs. 7(3-13] vs. 7(3-14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous (p = 0.025), musculoskeletal (p = 0.029), renal (p = 0.027) and cardiorespiratory (p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive (p = 0.034) and exhibited higher anti-dsDNA titres (p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia (p = 0.002), thrombocytopenia (p = 0.004) or low complement (p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. CONCLUSIONS: Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and "classic" autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.


Assuntos
Progressão da Doença , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Índice de Gravidade de Doença , Adolescente , Idade de Início , Criança , Técnicas de Laboratório Clínico , Estudos de Coortes , Feminino , Humanos , Masculino , Fatores Sexuais , Reino Unido
11.
Public Health ; 182: 110-115, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32251876

RESUMO

OBJECTIVES: Contact tracing following identification of tuberculosis (TB) is well established. However, evaluation of this activity, particularly for laryngeal TB, is limited. We compare contact tracing and outcomes in response to laryngeal TB with sputum-smear-positive pulmonary TB (ss + pTB) and consider the public health response in light of our findings. STUDY DESIGN: This study is a comparative secondary analysis of retrospective data, extracted from TB surveillance systems, to determine differences in contact tracing process and outcomes between two groups. METHODS: Cases of laryngeal TB (without ss + pTB) notified in England between 2012 and 2016 were selected and matched to ss + pTB controls. Number of contacts identified and screened, along with screening outcomes were gathered from local databases. RESULTS: There were 44 laryngeal TB cases who met inclusion criteria. The median number of contacts identified per case was 3 and 4 for controls (P = 0.04). Median number of contacts screened was 3 for cases and 4 for controls. The percentage of contacts with TB was 9.7 for cases and 20.3 for controls (P < 0.01). CONCLUSION: We observed a small difference, between case and control groups, in number of contacts identified but not number screened, indicative of a broadly similar approach to contact tracing. Conversely, the difference in screening outcomes between the groups was significant. These findings highlight a potential need to further understand infectivity of laryngeal TB; and consider possible implications for public health practice.


Assuntos
Busca de Comunicante/métodos , Tuberculose Laríngea/epidemiologia , Adulto , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Saúde Pública , Prática de Saúde Pública , Estudos Retrospectivos , Escarro/microbiologia , Tuberculose Pulmonar/epidemiologia
12.
Radiology ; 293(2): 405-411, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31526255

RESUMO

Background Detection of vertebral fractures (VFs) aids in management of osteoporosis and targeting of fracture prevention therapies. Purpose To determine whether convolutional neural networks (CNNs) can be trained to identify VFs at VF assessment (VFA) performed with dual-energy x-ray absorptiometry and if VFs identified by CNNs confer a similar prognosis compared with the expert reader reference standard. Materials and Methods In this retrospective study, 12 742 routine clinical VFA images obtained from February 2010 to December 2017 and reported as VF present or absent were used for CNN training and testing. All reporting physicians were diagnostic imaging specialists with at least 10 years of experience. Randomly selected training and validation sets were used to produce a CNN ensemble that calculates VF probability. A test set (30%; 3822 images) was used to assess CNN agreement with the human expert reader reference standard and CNN prediction of incident non-VFs. Statistical analyses included area under the receiver operating characteristic curve, two-tailed Student t tests, prevalence- and bias-adjusted κ value, Kaplan-Meier curves, and Cox proportional hazard models. Results This study included 12 742 patients (mean age, 76 years ± 7; 12 013 women). The CNN ensemble demonstrated an area under the receiver operating characteristic curve of 0.94 (95% confidence interval [CI]: 0.93, 0.95) for VF detection that corresponded to sensitivity of 87.4% (534 of 611), specificity of 88.4% (2838 of 3211), and prevalence- and bias-adjusted κ value of 0.77. On the basis of incident fracture data available for 2813 patients (mean follow up, 3.7 years), hazard ratios adjusted for baseline fracture probability were 1.7 (95% CI: 1.3, 2.2) for CNN versus 1.8 (95% CI: 1.3, 2.3) for expert reader-detected VFs for incident non-VF and 2.3 (95% CI: 1.5, 3.5) versus 2.4 (95% CI: 1.5, 3.7) for incident hip fracture. Conclusion Convolutional neural networks can identify vertebral fractures on vertebral fracture assessment images with high accuracy, and these convolutional neural network-identified vertebral fractures predict clinical fracture outcomes. © RSNA, 2019 Online supplemental material is available for this article.


Assuntos
Absorciometria de Fóton , Fraturas do Quadril/diagnóstico por imagem , Redes Neurais de Computação , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos
13.
Lupus ; 28(5): 613-620, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30871425

RESUMO

BACKGROUND: Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC). METHODS: UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann-Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis. RESULTS: Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4-8 and 10-14 months post-renal biopsy and last follow-up, in terms of renal British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141-390) days after MMF treatment, and 151 (117-305) days following IVCYC ( p = 0.17). Time to renal flare was 451 (157-1266) days for MMF, and 343 (198-635) days for IVCYC ( p = 0.47). CONCLUSION: This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Administração Intravenosa , Adolescente , Idade de Início , Criança , Estudos de Coortes , Feminino , Humanos , Rim/patologia , Masculino , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Reino Unido
14.
J Dairy Sci ; 102(7): 6555-6558, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31128868

RESUMO

Precision dairy monitoring technologies have become increasingly popular for recording rumination and feeding behaviors in dairy cattle. The objective of this study was to validate the rumination and feeding time functions of the CowManager SensOor (Agis, Harmelen, the Netherlands) against visual observation in dairy heifers. The study took place over a 44-d period beginning June 1, 2016. Holstein heifers equipped with CowManager SensOor tags attached according to manufacturer specifications (n = 49) were split into 2 groups based on age, diet, and housing type. Group 1 heifers (n = 24) were calves (mean ± SD) 2.0 ± 2.7 mo in age, fed hay and calf starter, and housed on a straw-bedded pack. Group 2 heifers (n = 25) were 17.0 ± 1.3 mo in age, fed a TMR, confirmed pregnant, and housed in freestalls. Visual observation shifts occurred at 1500, 1700, 1900, and 2100 h. Each heifer was observed for 2 hour-long periods, with both observation periods occurring on the same day. Visual observations were collected using a synchronized watch, and "start" and "stop" times were recorded for each rumination and feeding event. For correlations, data from CowManager SensOor tags and observations were averaged, so a single 1-h observation was provided per animal, reducing the potential for confounding repeated measures being collected for each animal. Concordance correlations (CCC; epiR package; R Foundation for Statistical Computing, Vienna, Austria) and Pearson correlations (r; CORR procedure; SAS Institute Inc., Cary, NC) were used to calculate association between visual observations and technology-recorded behaviors. Visually observed rumination time was correlated with the CowManager SensOor (r = 0.63, CCC = 0.55). Visually observed feeding time was also correlated with the CowManager SensOor (r = 0.88, CCC = 0.72). The difference between technology-recorded data and visual observation was treated as the dependent variable in a mixed linear model (MIXED procedure of SAS). Time of day, age in months, and group were treated as fixed effects. Individual heifers were treated as random and repeated effects. The effects of time of day, age, and group on rumination and feeding times were not significant. The CowManager SensOor was more effective at recording feeding behavior than rumination behavior in dairy heifers. The CowManager SensOor can be used to provide relatively accurate measures of feeding time in heifers, but its rumination time function should be used with caution.


Assuntos
Bovinos/fisiologia , Comportamento Alimentar , Rúmen/metabolismo , Ração Animal/análise , Animais , Feminino
15.
Support Care Cancer ; 26(9): 3055-3061, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29564621

RESUMO

BACKGROUND: The most commonly used antibacterial prophylaxis during autologous stem cell transplants (ASCT) for multiple myeloma (MM) involves a fluoroquinolone, such as ciprofloxacin or levofloxacin. We assessed the impact of adding doxycycline to ciprofloxacin as routine antibacterial prophylaxis in these patients. METHODS: We retrospectively reviewed electronic medical records and our ASCT database to analyze rates and types of bacterial infections in MM patients who underwent ASCT in our institution. RESULTS: Among 419 patients, 118 received ciprofloxacin alone (cipro group), and 301 ciprofloxacin and doxycycline (cipro-doxy group). Neutropenic fever (NF) developed in 63 (53%) and 108 (36%) patients of the cipro and cipro-doxy groups, respectively (p = 0.010). The number of documented bacteremic episodes was 13 (11%) and 14 (4.7%) in the two groups, respectively (p = 0.017). Antimicrobial resistance and Clostridium difficile infections were uncommon. Transplant-related mortality was 1% in both groups. CONCLUSIONS: The addition of doxycycline to standard prophylaxis with ciprofloxacin seems to reduce the number of NF episodes and documented bacterial infections in patients with MM undergoing ASCT, without increasing rate of serious complications.


Assuntos
Infecções Bacterianas/prevenção & controle , Ciprofloxacina/uso terapêutico , Doxiciclina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo
16.
Lupus ; 26(12): 1285-1290, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28361566

RESUMO

Objectives The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients' classification criteria evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period). Results A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012. Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Reumatologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino
17.
J Fish Dis ; 40(5): 649-659, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27594170

RESUMO

Asian shrimp farming industry has experienced massive production losses due to a disease caused by toxins of Vibrio bacteria, known as early mortality syndrome/acute hepatopancreatic necrosis disease (EMS/AHPND) for the last 5 years. The disease can cause up to 100% cumulative pond mortality within a week. The objective of this study was to identify factors associated with AHPND occurrence on shrimp farms. A case-control study was carried out on shrimp farms in four provinces of Thailand. Factors related to farm characteristics, farm management, pond and water preparation, feed management, post-larvae (PL) shrimp and stock management were evaluated. Multivariable logistic regression analysis identified factors affecting AHPND occurrence at the pond level. Chlorine treatment, reservoir availability, use of predator fish in the water preparation, culture of multiple shrimp species in one farm and increased PL stocking density contributed to an increased risk of AHPND infection, while delayed first day of feeding, polyculture and water ageing were likely to promote outbreak protection. Additionally, the source of PL was found to be associated with AHPND occurrence in shrimp ponds, which requires further study at the hatchery level. Identification of these factors will facilitate the development of effective control strategies for AHPND on shrimp farms.


Assuntos
Aquicultura/métodos , Penaeidae/microbiologia , Penaeidae/fisiologia , Vibrio/fisiologia , Animais , Longevidade , Penaeidae/crescimento & desenvolvimento , Tailândia , Qualidade da Água
18.
Thorax ; 71(12): 1110-1118, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27516225

RESUMO

INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity.


Assuntos
Bronquiectasia/diagnóstico , Índice de Gravidade de Doença , Idoso , Bronquiectasia/mortalidade , Bronquiectasia/fisiopatologia , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Qualidade de Vida , Medição de Risco/métodos
20.
Diabetes Obes Metab ; 18(7): 725-8, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26936426

RESUMO

The aim of the present analysis was to evaluate the efficacy of the glucagon-like peptide-1 receptor agonist liraglutide in Latino/Hispanic individuals with type 2 diabetes, in addition to comparing its treatment effects with those observed in non-Latino/Hispanic individuals. Analyses were performed on patient-level data from a subset of individuals self-defined as Latino/Hispanic from four phase III studies, the LEAD-3, LEAD-4, LEAD-6 and 1860-LIRA-DPP-4 trials. Endpoints included change in glycated haemoglobin (HbA1c) and body weight from baseline. In Latino/Hispanic patients (n = 505; 323 treated with liraglutide) after 26 weeks, mean HbA1c reductions were significantly greater with both liraglutide 1.2 and 1.8 mg versus comparator or placebo in the LEAD-3 and LEAD-4 studies, and with 1.8 mg liraglutide in the 1860-LIRA-DPP-4 trial. In LEAD-3 both doses led to significant differences in body weight change among Latino/Hispanic patients versus the comparator. With 1.8 mg liraglutide, difference in weight change was significant only in the 1860-LIRA-DPP-4 trial versus sitagliptin. For both endpoints Latino/Hispanic and non-Latino/Hispanic patients responded to liraglutide similarly. In summary, liraglutide is efficacious for treatment of type 2 diabetes in Latino/Hispanic patients, with a similar efficacy to that seen in non-Latino/Hispanic patients.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hispânico ou Latino , Hipoglicemiantes/administração & dosagem , Liraglutida/administração & dosagem , Glicemia/metabolismo , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 2/etnologia , Método Duplo-Cego , Esquema de Medicação , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Liraglutida/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA