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Sökning: WFRF:(Fazel J.)

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1.
  • Valassi, E., et al. (författare)
  • High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
  • 2019
  • Ingår i: European Journal of Endocrinology. - 0804-4643. ; 181:5, s. 461-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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2.
  • Goodwin, G. M., et al. (författare)
  • Evidence-based guidelines for treating bipolar disorder : Revised third edition recommendations from the British Association for Psychopharmacology
  • 2016
  • Ingår i: Journal of Psychopharmacology. - : SAGE PUBLICATIONS LTD. - 0269-8811 .- 1461-7285. ; 30:6, s. 495-553
  • Forskningsöversikt (refereegranskat)abstract
    • The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.
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3.
  • Rosa, Isabel M. D., et al. (författare)
  • Multiscale scenarios for nature futures
  • 2017
  • Ingår i: Nature Ecology & Evolution. - 2397-334X. ; 1:10, s. 1416-1419
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Targets for human development are increasingly connected with targets for nature, however, existing scenarios do not explicitly address this relationship. Here, we outline a strategy to generate scenarios centred on our relationship with nature to inform decision-making at multiple scales.
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4.
  • Au, C. E., et al. (författare)
  • Compartmentalization of membrane trafficking, glucose transport, glycolysis, actin, tubulin and the proteasome in the cytoplasmic droplet/Hermes body of epididymal sperm
  • 2015
  • Ingår i: Open Biology. - 2046-2441. ; 5:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Discovered in 1909 by Retzius and described mainly by morphology, the cytoplasmic droplet of sperm (renamed here the Hermes body) is conserved among all mammalian species but largely undefined at the molecular level. Tandem mass spectrometry of the isolated Hermes body from rat epididymal sperm characterized 1511 proteins, 43 of which were localized to the structure in situ by light microscopy and two by quantitative electron microscopy localization. Glucose transporter 3 (GLUT-3) glycolytic enzymes, selected membrane traffic and cytoskeletal proteins were highly abundant and concentrated in the Hermes body. By electron microscope gold antibody labelling, the Golgi trafficking protein TMED7/p27 localized to unstacked flattened cisternae of the Hermes body, as did GLUT-3, the most abundant protein. Its biogenesis was deduced through the mapping of protein expression for all 43 proteins during male germ cell differentiation in the testis. It is at the terminal step 19 of spermiogenesis that the 43 characteristic proteins accumulated in the nascent Hermes body.
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5.
  • Au, C. E., et al. (författare)
  • Expression, sorting, and segregation of Golgi proteins during germ cell differentiation in the testis
  • 2015
  • Ingår i: Molecular Biology of the Cell. - 1059-1524. ; 26:22, s. 4015-4032
  • Tidskriftsartikel (refereegranskat)abstract
    • The molecular basis of changes in structure, cellular location, and function of the Golgi apparatus during male germ cell differentiation is unknown. To deduce cognate Golgi proteins, we isolated germ cell Golgi fractions, and 1318 proteins were characterized, with 20 localized in situ. The most abundant protein, GL54D of unknown function, is characterized as a germ cell-specific Golgi-localized type II integral membrane glycoprotein. TM9SF3, also of unknown function, was revealed to be a universal Golgi marker for both somatic and germ cells. During acrosome formation, several Golgi proteins (GBF1, GPP34, GRASP55) localize to both the acrosome and Golgi, while GL54D, TM9SF3, and the Golgi trafficking protein TMED7/p27 are segregated from the acrosome. After acrosome formation, GL54D, TM9SF3, TMED4/p25, and TMED7/p27 continue to mark Golgi identity as it migrates away from the acrosome, while the others (GBF1, GPP34, GRASP55) remain in the acrosome and are progressively lost in later steps of differentiation. Cytoplasmic HSP70.2 and the endoplasmic reticulum luminal protein-folding enzyme PDILT are also Golgi recruited but only during acrosome formation. This resource identifies abundant Golgi proteins that are expressed differentially during mitosis, meiosis, and postacrosome Golgi migration, including the last step of differentiation.
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7.
  • Chen, Qi, et al. (författare)
  • Predicting suicide attempt or suicide death following a visit to psychiatric specialty care : A machine learning study using Swedish national registry data
  • 2020
  • Ingår i: PLoS Medicine. - San Francisco : Public Library of Science. - 1549-1277 .- 1549-1676. ; 17:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Suicide is a major public health concern globally. Accurately predicting suicidal behavior remains challenging. This study aimed to use machine learning approaches to examine the potential of the Swedish national registry data for prediction of suicidal behavior.Methods and findings: The study sample consisted of 541,300 inpatient and outpatient visits by 126,205 Sweden-born patients (54% female and 46% male) aged 18 to 39 (mean age at the visit: 27.3) years to psychiatric specialty care in Sweden between January 1, 2011 and December 31, 2012. The most common psychiatric diagnoses at the visit were anxiety disorders (20.0%), major depressive disorder (16.9%), and substance use disorders (13.6%). A total of 425 candidate predictors covering demographic characteristics, socioeconomic status (SES), electronic medical records, criminality, as well as family history of disease and crime were extracted from the Swedish registry data. The sample was randomly split into an 80% training set containing 433,024 visits and a 20% test set containing 108,276 visits. Models were trained separately for suicide attempt/death within 90 and 30 days following a visit using multiple machine learning algorithms. Model discrimination and calibration were both evaluated. Among all eligible visits, 3.5% (18,682) were followed by a suicide attempt/death within 90 days and 1.7% (9,099) within 30 days. The final models were based on ensemble learning that combined predictions from elastic net penalized logistic regression, random forest, gradient boosting, and a neural network. The area under the receiver operating characteristic (ROC) curves (AUCs) on the test set were 0.88 (95% confidence interval [CI] = 0.87-0.89) and 0.89 (95% CI = 0.88-0.90) for the outcome within 90 days and 30 days, respectively, both being significantly better than chance (i.e., AUC = 0.50) (p < 0.01). Sensitivity, specificity, and predictive values were reported at different risk thresholds. A limitation of our study is that our models have not yet been externally validated, and thus, the generalizability of the models to other populations remains unknown.Conclusions: By combining the ensemble method of multiple machine learning algorithms and high-quality data solely from the Swedish registers, we developed prognostic models to predict short-term suicide attempt/death with good discrimination and calibration. Whether novel predictors can improve predictive performance requires further investigation. Author summary Why was this study done? Suicidal behavior is overrepresented in people with mental illness and contributes to the substantial public health burden of psychiatric conditions. Accurately predicting suicidal behavior has long been challenging. The potential of applying machine learning to linked national datasets to predict suicidal behavior remains unknown. What did the researchers do and find? We identified a sample of 541,300 inpatient and outpatient visits to psychiatric specialty care in Sweden during 2011 and 2012. The sample was then divided into a training dataset and a test dataset. We first trained prediction models separately for suicide attempt/death within 90 days and 30 days following a visit to psychiatric specialty care, using 4 different machine learning algorithms. We then used an ensemble method to combine the performance of the trained models with the intention to achieve an overall performance superior than each individual model. The final model based on the ensemble method achieved the best predictive performance. This model was applied to test dataset and showed good model discrimination and calibration for both the 90-day and 30-day outcomes. What do these findings mean? Our findings suggest that combining machine learning with registry data has the potential to accurately predict short-term suicidal behavior. An approach combining 4 machine learning methods showed an overall predictive performance slightly better than each individual model.
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8.
  • Gannon, J., et al. (författare)
  • ARFGAP1 Is Dynamically Associated with Lipid Droplets in Hepatocytes
  • 2014
  • Ingår i: Plos One. - 1932-6203. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ARF GTPase Activating Protein 1 (ARFGAP1) associates mainly with the cytosolic side of Golgi cisternal membranes where it participates in the formation of both COPI and clathrin-coated vesicles. In this study, we show that ARFGAP1 associates transiently with lipid droplets upon addition of oleate in cultured cells. Also, that addition of cyclic AMP shifts ARFGAP1 from lipid droplets to the Golgi apparatus and that overexpression and knockdown of ARFGAP1 affect lipid droplet formation. Examination of human liver tissue reveals that ARFGAP1 is found associated with lipid droplets at steady state in some but not all hepatocytes.
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9.
  • Mohammadi Fazel, A., et al. (författare)
  • A process for identifying national solutions to challenges faced in developing countries in reporting to environmental conventions : Insight from the facilitating national reporting to the rio conventions project
  • 2015
  • Ingår i: International Journal of Environmental Research. - : Graduate Faculty of Environment, University of Tehran. - 1735-6865. ; 9:4, s. 1163-1172
  • Tidskriftsartikel (refereegranskat)abstract
    • Almost all countries in the world are party to the Rio Conventions. This entails a number of responsibilities, including reporting periodically on aspects of environmental health and national implementation of the convention. These reports can cover hundreds of pages, so completing reports is often a significant undertaking. Since countries can be party to numerous Multilateral Environmental Agreements (MEAs), they may have several such reports to prepare at any one time, often using similar information. This article shares insights from a project that piloted nationally-driven, integrated approaches to reporting to the Rio Conventions and developed flexible methods for enhancing the national reporting process, in a way that is relevant for a particular country. The project found that a focus on collaborative institutional arrangements and building capacity as a nation, rather than as a series of departments, could enhance this reporting process. These lessons can inform decisions of United Nations agencies, MEA secretariats, Country Parties to these MEAs and the wider sustainability community to reduce the reporting burden and increase the synergistic implementation of environmental conventions.
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