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Sökning: WFRF:(Khoury D)

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  • 2021
  • swepub:Mat__t
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  • Terracciano, A, et al. (författare)
  • National character does not reflect mean personality trait levels in 49 cultures
  • 2005
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 310:5745, s. 96-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Most people hold beliefs about personality characteristics typical of members of their own and others' cultures. These perceptions of national character may be generalizations from personal experience, stereotypes with a "kernel of truth," or inaccurate stereotypes. We obtained national character ratings of 3989 people from 49 cultures and compared them with the average personality scores of culture members assessed by observer ratings and self-reports. National character ratings were reliable but did not converge with assessed traits. Perceptions of national character thus appear to be unfounded stereotypes that may serve the function of maintaining a national identity.
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  • Clark, K, et al. (författare)
  • Stigma, displacement stressors and psychiatric morbidity among displaced Syrian men who have sex with men (MSM) and transgender women: a cross-sectional study in Lebanon
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:5, s. e046996-
  • Tidskriftsartikel (refereegranskat)abstract
    • Displaced Syrians face psychiatric morbidity often resulting from displacement-related stressors (eg, resource scarcity). Both men who have sex with men (MSM) and transgender women among the displaced Syrians are particularly vulnerable to mental health challenges given that they also often face stigma-related stressors (eg, discrimination).MethodsBetween January and December 2019 in greater Beirut, 258 Lebanese-born MSM and transgender women and 230 displaced Syrian MSM and transgender women were recruited via respondent-driven sampling to complete an in-person survey assessing displacement-related stressors, stigma-related stressors, depression, anxiety and post-traumatic stress disorder. In the total sample, we first documented the prevalence of psychiatric morbidity among the displaced Syrians; we then assessed associations among displacement-related and stigma-related stressors and each psychiatric outcome.ResultsSixty-three per cent of Syrian participants met criteria for depression compared with 43.8% of Lebanese participants (p<0.001); 21.3% of Syrians met criteria for severe anxiety compared with 13.1% of Lebanese participants (p<0.05) and 33.0% of Syrians met criteria for post-traumatic stress disorder compared with 18.4% of Lebanese participants (p<0.001). Among Syrian MSM and transgender women, sociodemographic characteristics, displacement-related stressors and stigma-related stressors were uniquely associated with psychiatric morbidity.ConclusionDisplaced Syrian MSM and transgender women experience higher levels of psychiatric comorbidities than Lebanese MSM and transgender women in part due to compounding exposure to displacement-related stressors and stigma-related stressors. Informed by tenets of minority stress theory and intersectionality theory, we discuss mental health intervention implications and future directions.
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  • Eriksson, Kimmo, et al. (författare)
  • Perceptions of the appropriate response to norm violation in 57 societies
  • 2021
  • Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about peoples preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in peoples perception of the appropriateness of norm violations.
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  • Hautmann, R, et al. (författare)
  • Urinary diversion
  • 2006
  • Ingår i: Bladder Tumors. ; , s. 239-239
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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  • Khoury, J. D., et al. (författare)
  • The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
  • 2022
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36, s. 1703-1719
  • Tidskriftsartikel (refereegranskat)abstract
    • The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
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  • Macari, F., et al. (författare)
  • TRM6/61 connects PKCα with translational control through tRNAiMet stabilization : impact on tumorigenesis
  • 2016
  • Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 35:14, s. 1785-1796
  • Tidskriftsartikel (refereegranskat)abstract
    • Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C [alpha] (PKC[alpha]) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAiMet), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAiMet. In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAiMet-overexpressing cells, PKC[alpha] overexpression decreased tRNAiMet expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAiMet expression with decreased expression of PKC[alpha] mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKC[alpha] tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.
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  • Roemer, Frank W., et al. (författare)
  • Tibiofemoral Joint Osteoarthritis: Risk Factors for MR-depicted Fast Cartilage Loss over a 30-month Period in the Multicenter Osteoarthritis Study
  • 2009
  • Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 1527-1315 .- 0033-8419. ; 252:3, s. 772-780
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To assess baseline factors that may predict fast tibiofemoral cartilage loss over a 30-month period. Materials and Methods: The Multicenter Osteoarthritis (MOST) study is a longitudinal study of individuals who have or who are at high risk for knee osteoarthritis. The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all participants. Magnetic resonance (MR) images were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. Only knees with minimal baseline cartilage damage (WORMS <= 2.5) were included. Fast cartilage loss was defined as a WORMS of at least 5 (large full-thickness loss, less than 75% of the subregion) in any subregion at 30-month follow-up. The relationships of age, sex, body mass index (BMI), ethnicity, knee alignment, and several MR features (eg, bone marrow lesions, meniscal damage and extrusion, and synovitis or effusion) to the risk of fast cartilage loss were assessed by using a multivariable logistic regression model. Results: Of 347 knees, 90 (25.9%) exhibited cartilage loss, and only 20 (5.8%) showed fast cartilage loss. Strong predictors of fast cartilage loss were high BMI (adjusted odds ratio [OR], 1.11; 95% confidence interval [CI]: 1.01, 1.23), the presence of meniscal tears (adjusted OR, 3.19; 95% CI: 1.13, 9.03), meniscal extrusion (adjusted OR, 3.62; 95% CI: 1.34, 9.82), synovitis or effusion (adjusted OR, 3.36; 95% CI: 0.91, 12.4), and any high-grade MR-depicted feature (adjusted OR, 8.99; 95% CI: 3.23, 25.1). Conclusion: In participants with minimal baseline cartilage damage, the presence of high BMI, meniscal damage, synovitis or effusion, or any severe baseline MR-depicted lesions was strongly associated with an increased risk of fast cartilage loss. Patients with these risk factors may be ideal subjects for preventative or treatment trials. (C) RSNA, 2009
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  • Zabriskie, Matthew S., et al. (författare)
  • BCR-ABL1 Compound Mutations Combining Key Kinase Domain Positions Confer Clinical Resistance to Ponatinib in Ph Chromosome-Positive Leukemia
  • 2014
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 26:3, s. 428-442
  • Tidskriftsartikel (refereegranskat)abstract
    • Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph+) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph+ leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome.
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  • Carniato, S., et al. (författare)
  • Thomson-resonant interference effects in elastic x-ray scattering near the Cl K edge of HCl
  • 2012
  • Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 137:9, s. 094311-
  • Tidskriftsartikel (refereegranskat)abstract
    • We experimentally observed interference effects in elastic x-ray scattering from gas-phase HCl in the vicinity of the Cl Kedge. Comparison to theory identifies these effects as interference effects between non-resonant elastic Thomson scattering and resonant Raman scattering. The results indicate the non-resonant Thomson and resonant Raman contributions are of comparable strength. The measurements also exhibit strong polarization dependence, allowing an easy identification of the resonant and non-resonant contributions.
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  • Jacquot, F., et al. (författare)
  • Lysophophatidylcholine 16:0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3
  • 2022
  • Ingår i: Pain. - : International Association for the Study of Pain. - 0304-3959 .- 1872-6623. ; 163:10, s. 1999-2013
  • Tidskriftsartikel (refereegranskat)abstract
    • Rheumatic diseases are often associated to debilitating chronic pain, which remains difficult to treat and requires new therapeutic strategies. We had previously identified lysophosphatidylcholine (LPC) in the synovial fluids from few patients and shown its effect as a positive modulator of acid-sensing ion channel 3 (ASIC3) able to induce acute cutaneous pain in rodents. However, the possible involvement of LPC in chronic joint pain remained completely unknown. Here, we show, from 2 independent cohorts of patients with painful rheumatic diseases, that the synovial fluid levels of LPC are significantly elevated, especially the LPC16:0 species, compared with postmortem control subjects. Moreover, LPC16:0 levels correlated with pain outcomes in a cohort of osteoarthritis patients. However, LPC16:0 do not appear to be the hallmark of a particular joint disease because similar levels are found in the synovial fluids of a second cohort of patients with various rheumatic diseases. The mechanism of action was next explored by developing a pathology-derived rodent model. Intra-articular injections of LPC16:0 is a triggering factor of chronic joint pain in both male and female mice, ultimately leading to persistent pain and anxiety-like behaviors. All these effects are dependent on ASIC3 channels, which drive sufficient peripheral inputs to generate spinal sensitization processes. This study brings evidences from mouse and human supporting a role for LPC16:0 via ASIC3 channels in chronic pain arising from joints, with potential implications for pain management in osteoarthritis and possibly across other rheumatic diseases.
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  • Khoury, L, et al. (författare)
  • Management of Thoracic and Lumbar Spine Fractures: Is MRI Necessary in Patients without Neurological Deficits?
  • 2019
  • Ingår i: The American surgeon. - : SAGE Publications. - 1555-9823 .- 0003-1348. ; 85:3, s. 306-311
  • Tidskriftsartikel (refereegranskat)abstract
    • MRI after a CTscan for thoracolumbar spine (TLS) trauma has become commonplace because of the concerns for detection of posterior ligamentous complex injuries in the absence of substantial scientific evidence to support its use. We hypothesized that MRI scans were not necessary in the clinical management of TLS fractures. A prospective study was conducted at our Level I trauma center. A total of 39 neurologically intact patients with TLS fracture on CT were enrolled. The patients’ CT scan and neurological examination were reviewed by a senior neurosurgeon, who determined clinical management based on these data. Assessment was repeated after an MRI of the spine was performed, and a second clinical plan was devised. The two treatment schemes were then compared. MRI resulted in a change in clinical management in 15 per cent of patients. Ten per cent of patients changed from requiring a brace to no brace and merely observation alone. In no patient planned for nonoperative care was surgery deemed necessary after completion of MRI. Among five patients with initial plans for operative intervention, two avoided surgery after the MRI. MRI has little impact on the management of patients with CT-proven thoracic and lumbar spine fractures. Only when surgery is planned based on CT studies does an MRI seem to assist with determining optimal care.
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  • Kupari, J, et al. (författare)
  • Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1510-
  • Tidskriftsartikel (refereegranskat)abstract
    • Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.
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  • Nguyen, Thanh N, et al. (författare)
  • Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
  • 2023
  • Ingår i: Neurology. - 1526-632X. ; 100:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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  • Ohashi, Kenjirou, et al. (författare)
  • Diagnostic accuracy of 3D color volume-rendered CT images for peroneal tendon dislocation in patients with acute calcaneal fractures
  • 2015
  • Ingår i: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 56:2, s. 190-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Use of three-dimensional (3D) color volume-rendered (VR) images has been reported to be more time-efficient compared to that of cross-sectional computed tomography (CT) images for the diagnosis of peroneal tendon dislocation. However, the diagnostic performance of this technique has not been studied. Purpose: To test diagnostic accuracy of 3D color VR CT images of ankle for peroneal tendon dislocation in patients with acute calcaneal fractures. Material and Methods: The study consisted of 121 ankle CT studies from 105 consecutive patients (85 men, 20 women; mean age, 42 years; age range, 16-75 years) with acute calcaneal fractures. Peroneal tendon dislocation was diagnosed on multiplanar CT images by consensus of two experienced musculoskeletal radiologists, which served as the reference standard. Three other musculoskeletal radiologists independently reviewed 3D images alone on a work-station. The readers determined whether or not there was peroneal tendon dislocation using three degrees of certainty (definite, probable, and possible). Diagnostic performance of 3D images for peroneal tendon dislocation was evaluated by calculating the sensitivities, specificities, and area under the receiver-operating characteristic (ROC) curves. Results: Forty-eight (40%) out of 121 studies showed peroneal tendon dislocation based on the expert readings using multiplanar reformatted images. Sensitivities/specificities of 3D images measured 0.92/0.81, 0.88/0.90, and 0.81/0.92 for three readers, respectively. The area under the proper binormal ROC curve based on all three readers (0.93, 0.94, and 0.92) measured 0.93 with a 95% confidence interval of 0.89-0.98. Conclusion: Diagnostic accuracy of 3D images is comparable to, but not as good as that of MPR images for the diagnosis of peroneal tendon dislocation in patients with acute calcaneal fractures.
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  • Roemer, Frank W., et al. (författare)
  • The association between meniscal damage of the posterior horns and localized posterior synovitis detected on T1-weighted contrast-enhanced MRI-The MOST study
  • 2013
  • Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 42:6, s. 573-581
  • Forskningsöversikt (refereegranskat)abstract
    • Objective: Synovitis is thought to be a secondary phenomenon in the osteoarthritis (OA) process and the menisci might be triggers of localized synovitis. The aim was to assess the cross-sectional associations of posterior horn meniscal damage with perimeniscal synovitis, and with synovitis posterior to the posterior cruciate ligament (PCL) using contrast enhanced (CE) MRI. Design: The Multicenter Osteoarthritis (MOST) Study is a longitudinal observational study of subjects with or at risk for knee OA. Subjects are a subset of MOST who were examined with 1.5 T CE MRI and had semiquantitative synovitis (scored from 0 to 2 at 11 locations) and meniscal readings (scored with WORMS from 0 to 4) available. Logistic regression was used to assess the association of posterior meniscal damage and perimeniscal synovitis in the same compartment, and between posterior meniscal damage and synovitis posterior to the PCL. Results: Three hundred and seventy seven knees were included (mean age 61.1 years +/- 6.9, mean BMI 29.6 +/- 4.9, 44.3% women). The odds for ipsi-compartmental perimeniscal synovitis were increased for knees with medial posterior horn meniscal damage (adjusted odds ratio [aOR] 2.5, 95% confidence intervals [95% CI] 1.3,4.8), but not for lateral damage (aOR 1.7, 95% CI 0.4,6.6). No positive associations were found for meniscal damage and presence of synovitis posterior to the PCL (aOR 0.9, 95% CI 0.6,1.5). Conclusions: Meniscal damage of the posterior horns is associated with ipsi-compartmental perimensical synovitis. No associations were found for posterior horn meniscal damage with synovitis posterior to the PCL, which suggests that synovitis posterior to the PCL is likely to be triggered by different pathomechanisms. (C) 2013 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:573-581
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  • Ruifrok, Anneloes E, et al. (författare)
  • Study protocol : Differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: Individual patient data (IPD) meta-analysis and health economic evaluation
  • 2014
  • Ingår i: Systematic Reviews. - : Springer Science and Business Media LLC. - 2046-4053. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.Methods/designRandomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research.
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  • Signori, A, et al. (författare)
  • Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network
  • 2023
  • Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 94:1, s. 23-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.MethodsAll patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3–4.ResultsA total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria.ConclusionsContrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.
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  • Wiehager, Sara, et al. (författare)
  • Increased levels of cocaine and amphetamine regulated transcript in two animal models of depression and anxiety.
  • 2009
  • Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961 .- 1095-953X. ; 34, s. 375-380
  • Tidskriftsartikel (refereegranskat)abstract
    • The neurobiological bases of mood disorders remain elusive but both monoamines and neuropeptides may play important roles. The neuropeptide cocaine and amphetamine regulated transcript (CART) was shown to induce anxiety-like behavior in rodents, and mutations in the human CART gene are associated with depression and anxiety. We measured CART-like immunoreactivity (-LI) in genetic rat models of depression and anxiety, i.e. the Flinders Sensitive Line (FSL) and rats selected for High Anxiety-related Behavior (HAB) using a radioimmunoassay. CART-LI was significantly increased in the periaqueductal grey in FSL rats, whereas in the HAB strain it was increased in the hypothalamus, both compared with their respective controls. No line-dependent changes were found in the hippocampus, striatum or frontal cortex. Our results confirm human genetic studies indicating CART as a neurobiological correlate of depression and anxiety, and suggest that its differential regulation in specific brain regions may play a role for the behavioral phenotypes.
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