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Sökning: WFRF:(Akhtar D)

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1.
  • 2021
  • swepub:Mat__t
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  • Niemi, MEK, et al. (författare)
  • 2021
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  • Glasbey, JC, et al. (författare)
  • 2021
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  • 2021
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  • Kanai, M, et al. (författare)
  • 2023
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  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Murari, A., et al. (författare)
  • A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
  • 2024
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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14.
  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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23.
  • Drake, Thomas M., et al. (författare)
  • Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction
  • 2019
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 45:12, s. 2319-2324
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Introduction: Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods: A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results: 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions: Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups.
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24.
  • Acciarresi, M., et al. (författare)
  • Prestroke CHA(2)DS(2)-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study
  • 2017
  • Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 26:6, s. 1363-1368
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS < 3 or >= 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.
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25.
  • Altavilla, R., et al. (författare)
  • Anticoagulation After Stroke in Patients With Atrial Fibrillation: To Bridge or Not With Low-Molecular-Weight Heparin?
  • 2019
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:8, s. 2093-2100
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
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26.
  • Paciaroni, M., et al. (författare)
  • Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: Time to initiation of oral anticoagulant therapy and outcomes
  • 2018
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background—In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results—HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions—In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. © 2018 The Authors.
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  • Paciaroni, M., et al. (författare)
  • Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema The ALESSA Score Study
  • 2017
  • Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 48:3, s. 726-732
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purposes-This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods-The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age 80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results-The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions-In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.
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  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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30.
  • ODonnell, Michael, et al. (författare)
  • Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
  • 2018
  • Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
  • Tidskriftsartikel (refereegranskat)abstract
    • Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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  • Paulus, A, et al. (författare)
  • Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells
  • 2016
  • Ingår i: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 6:11, s. e492-
  • Tidskriftsartikel (refereegranskat)abstract
    • The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation.
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32.
  • Akhtar, Farid, et al. (författare)
  • A new kind of age hardenable martensitic stainless steel with high strength and toughness
  • 2007
  • Ingår i: Ironmaking & steelmaking. - 0301-9233 .- 1743-2812. ; 34:4, s. 285-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Following analysis of typical age hardenable martensitic stainless steels, a new kind of maragingstainless was developed. The new maraging stainless steel showed high strength, ultimate tensilestrength (UTS) 5 1670 MPa, high toughness, K IC 5 83·9 MPa m1/2 and hardness as high as 478 HVin the age hardened condition. Microstructural study with an optical and transmission electron microscope revealed the typical microstructure of age hardenable stainless steel containing lathmartensite and precipitates. TixNi precipitates were identified by transmission electron microscopy, which were responsible for the increase in mechanical properties after age hardening. The results of natural salt spray test showed that the corrosion resistance of new maraging stainless steel approached to the corrosion resistance of 304L stainless steel.
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33.
  • Cumpstey, Ian, et al. (författare)
  • Amine-linked diglycosides : Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays
  • 2011
  • Ingår i: Beilstein Journal of Organic Chemistry. - : Beilstein Institut. - 2195-951X .- 1860-5397. ; 7, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Diglycose derivatives, consisting of two monosaccharides linked at non-anomeric positions by a bridging nitrogen atom, have been synthesised. Conversion of one of the precursor monosaccharide coupling components into an unsaturated derivative enhances its electrophilicity at the allylic position, facilitating coupling reactions. Mitsunobu coupling between nosylamides and 2,3-unsaturated-4-alcohols gave the 4-amino-pseudodisaccharides with inversion of configuration as single regio- and diastereoisomers. A palladium-catalysed coupling between an amine and a 2,3-unsaturated 4-trichloroacetimidate gave a 2-amino-pseudodisaccharide as the major product, along with other minor products. Derivatisation of the C=C double bond in pseudodisaccharides allowed the formation of Man(N4-6)Glc and Man(N4-6)Man diglycosides. The amine-linked diglycosides were found to show weak glycosidase inhibitory activity.
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34.
  • de Graaff, Anne M., et al. (författare)
  • Scalable psychological interventions for Syrian refugees in Europe and the Middle East : STRENGTHS study protocol for a prospective individual participant data meta-analysis
  • 2022
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The World Health Organization's (WHO) scalable psychological interventions, such as Problem Management Plus (PM+) and Step-by-Step (SbS) are designed to be cost-effective non-specialist delivered interventions to reduce symptoms of common mental disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD). The STRENGTHS consortium aims to evaluate the effectiveness, cost-effectiveness and implementation of the individual format of PM+ and its group version (gPM+), as well as of the digital SbS intervention among Syrian refugees in seven countries in Europe and the Middle East. This is a study protocol for a prospective individual participant data (IPD) meta-analysis to evaluate (1) overall effectiveness and cost-effectiveness and (2) treatment moderators of PM+, gPM+ and SbS with Syrian refugees. Methods and analysis Five pilot randomised controlled trials (RCTs) and seven fully powered RCTs conducted within STRENGTHS will be combined into one IPD meta-analytic dataset. The RCTs include Syrian refugees of 18 years and above with elevated psychological distress (Kessler Psychological Distress Scale (K10>15)) and impaired daily functioning (WHO Disability Assessment Schedule 2.0 (WHODAS 2.0>16)). Participants are randomised into the intervention or care as usual control group, and complete follow-up assessments at 1-week, 3-month and 12-month follow-up. Primary outcomes are symptoms of depression and anxiety (25-item Hopkins Symptom Checklist). Secondary outcomes include daily functioning (WHODAS 2.0), PTSD symptoms (PTSD Checklist for DSM-5) and self-identified problems (PSYCHLOPS). We will conduct a one-stage IPD meta-analysis using linear mixed models. Quality of evidence will be assessed using the GRADE approach, and the economic evaluation approach will be assessed using the CHEC-list. Ethics and dissemination Local ethical approval has been obtained for each RCT. This IPD meta-analysis does not require ethical approval. The results of this study will be published in international peer-reviewed journals.
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35.
  • De Nardis, L., et al. (författare)
  • Impact of mobility in cooperative spectrum sensing : Theory vs. simulation
  • 2012
  • Ingår i: Wireless Communication Systems (ISWCS), 2012 International Symposium on. - : IEEE. - 9781467307604 ; , s. 416-420
  • Konferensbidrag (refereegranskat)abstract
    • This work addresses the problem of cooperative spectrum sensing in cognitive radio networks, focusing on the impact of mobility on performance of cooperative sensing. First, a review of the most recent results on cooperative spectrum sensing is provided, resulting in the identification of measurement correlation and frame error rate in the reporting channel as the main parameters influencing the performance of cooperative sensing schemes. Next, the paper discusses the extension of the analysis to the case of mobile sensors, and determines the set of assumptions made in existing literature when taking into account mobility in sensing. The paper moves then to remove some of such assumptions, by presenting simulation results obtained in presence of realistic models for propagation in the considered area, as well as of a realistic mobility model. A comparison between theoretical derivation and simulation results shows that correlation among measurements taken by different sensors and the selected mobility model may significantly affect the sensing performance.
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39.
  • Larsson, K, et al. (författare)
  • The Saccharomyces cerevisiae SOP1 and SOP2 genes, which act in cation homeostasis, can be functionally substituted by the Drosophila lethal(2)giant larvae tumor suppressor gene.
  • 1998
  • Ingår i: The Journal of biological chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 273:50, s. 33610-8
  • Tidskriftsartikel (refereegranskat)abstract
    • By complementation of a salt-sensitive mutant of Saccharomyces cerevisiae, we cloned the SOP1 gene, encoding a 114.5-kDa protein of 1033 amino acids. Cells deleted for SOP1 exhibited sensitivity to sodium stress, but showed no sensitivity to general osmotic stress. Following exposure of sop1Delta cells to NaCl stress, the intracellular Na+ level and the Na+/K+ ratio rose to values significantly higher than in wild type cells. Deletion of SOP2, encoding a protein sharing 54% amino acid identity with Sop1p, produced only slight Na+ sensitivity. Cells carrying a sop1Deltasop2Delta double deletion became, however, hypersensitive to Na+ and exhibited increased sensitivity also to Li+ and K+, suggesting involvement of both SOP1 and SOP2 in cation homeostasis. The predicted amino acid sequences of Sop1p and Sop2p show significant homologies with the cytoskeletal-associated protein encoded by the Drosophila lethal(2)giant larvae tumor suppressor gene. Immunolocalization of Sop1p revealed a cytoplasmic distribution and cell fractionation studies showed that a significant fraction of Sop1p was recovered in a sedimentable fraction of the cytosolic material. Expression of a Drosophila l(2)gl cDNA in the sop1Deltasop2Delta strain partially restored the Na+ tolerance of the cells, indicating a functional relationship between the Sop proteins and the tumor suppressor protein, and a novel function in cell homeostasis for this family of proteins extending from yeast to human.
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40.
  • Li, Tongkuai, et al. (författare)
  • Kelvin-Helmholtz Waves and Magnetic Reconnection at the Earth's Magnetopause Under Southward Interplanetary Magnetic Field
  • 2023
  • Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 50:20
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Magnetospheric Multiscale (MMS) observations of a K-H wave event under southward IMF conditions, accompanied by ongoing magnetic reconnection. The nonlinear K-H waves are characterized by quasi-periodic fluctuations, the presence of low-density and high-speed ions, and variations in the boundary normal vectors at both the leading and trailing edges. Our observations reveal clear evidence of on-going magnetic reconnection through the identification of Alfvenic ion jets and the escape of energetic magnetospheric electrons. Among the 36 magnetopause current-sheet crossings in this event, 19 exhibit unambiguous signatures of reconnection at both the leading (7) and trailing (12) edges. Notably, the estimated current-sheet thicknesses at both edges are comparable to the ion-inertial scale, confirming the compression effect resulting from the large-scale evolution of the K-H waves. The reconnection jets potentially contribute to the suppression of K-H growth through boundary-layer broadening and the development of complex flow and magnetic field patterns.
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43.
  • Spaaij, J., et al. (författare)
  • The effect of a low-level psychological intervention (PM+) on post-migration living difficulties – Results from two studies in Switzerland and in the Netherlands
  • 2023
  • Ingår i: Comprehensive Psychiatry. - : Elsevier BV. - 0010-440X .- 1532-8384. ; 127
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims of the study: After arriving in host countries, most refugees are confronted with numerous post-migration stressors (e.g., separation from family, discrimination, and employment difficulties). Post-migration living difficulties (PMLDs) significantly contribute to the development and persistence of mental disorders. Effective treatment approaches focusing on reducing post-migration stress are urgently needed. The aim of the present study was to examine the effect of a brief psychological intervention, Problem Management Plus (PM+), on PMLDs among Syrian refugees in two European countries. Methods: We merged data from two single-blind feasibility trials with Syrian refugees experiencing elevated levels of psychological distress and impaired functioning in Switzerland (N = 59) and the Netherlands (N = 60). Participants were randomised to receive either five sessions of PM+ or an enhanced care-as-usual control condition. PMLDs were assessed at baseline and 3 months after the intervention. To estimate treatment effect on PMLD, linear mixed model analysis was performed. Results: Three months after the intervention, participants in the PM+ condition reported significantly fewer PMLDs compared to the control condition. Further analyses at item-level showed that interpersonal and family related PMLDs, such as “worries about family back home” significantly improved over time in the PM+ condition. Conclusions: This exploratory study suggests that brief psychological interventions have the potential to reduce PMLDs in refugees and asylum seekers. The reduction of post-migration stress in turn may subsequently lead to an overall reduction in psychological distress. Clinical Trial Numbers: BASEC Nr. 2017–0117 (Swiss trial) and NL61361.029.17, 7 September 2017 (Dutch trial). 
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44.
  • Tahir, M. J., et al. (författare)
  • Internet addiction and sleep quality among medical students during the COVID-19 pandemic : A multinational cross-sectional survey
  • 2021
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:11 November
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The emergence of the COVID-19 pandemic has affected the lives of many people, including medical students. The present study explored internet addiction and changes in sleep patterns among medical students during the pandemic and assessed the relationship between them. Methods A cross-sectional study was carried out in seven countries, the Dominican Republic, Egypt, Guyana, India, Mexico, Pakistan, and Sudan, using a convenience sampling technique, an online survey comprising demographic details, information regarding COVID-19, the Pittsburgh Sleep Quality Index (PSQI), and the Internet Addiction Test (IAT). Results In total, 2749 participants completed the questionnaire. Of the total, 67.6% scored above 30 in the IAT, suggesting the presence of an Internet addiction, and 73.5% scored equal and above 5 in the PSQI, suggesting poor sleep quality. Internet addiction was found to be significant predictors of poor sleep quality, causing 13.2% of the variance in poor sleep quality. Participants who reported COVID-19 related symptoms had disturbed sleep and higher internet addiction levels when compared with those who did not. Participants who reported a diagnosis of COVID-19 reported poor sleep quality. Those living with a COVID-19 diagnosed patient reported higher internet addiction and worse sleep quality compared with those who did not have any COVID-19 patients in their surroundings. Conclusion The results of this study suggest that internet addiction and poor sleep quality are two issues that require addressing amongst medical students. Medical training institutions should do their best to minimize their negative impact, particularly during the current COVID-19 pandemic.
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45.
  • Wang, Xin, et al. (författare)
  • The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells
  • 2016
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Inhibition of deubiquitinase (DUB) activity is a promising strategy for cancer therapy. VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Here we show that VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) in vitro, with comparatively weaker inhibitory activity towards UCHL5 (ubiquitin-C-terminal hydrolase-5). Exposure of multiple myeloma cells to VLX1570 resulted in thermostabilization of USP14 at therapeutically relevant concentrations. Transient knockdown of USP14 or UCHL5 expression by electroporation of siRNA reduced the viability of multiple myeloma cells. Treatment of multiple myeloma cells with VLX1570 induced the accumulation of proteasome-bound high molecular weight polyubiquitin conjugates and an apoptotic response. Sensitivity to VLX1570 was moderately affected by altered drug uptake, but was unaffected by overexpression of BCL2-family proteins or inhibitors of caspase activity. Finally, treatment with VLX1570 was found to lead to extended survival in xenograft models of multiple myeloma. Our findings demonstrate promising antiproliferative activity of VLX1570 in multiple myeloma, primarily associated with inhibition of USP14 activity.
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46.
  • Widenkvist, Erika, et al. (författare)
  • Intercalation and Ultrasonic Treatment of Graphite : a New Synthetic Route to Graphene
  • 2008
  • Konferensbidrag (refereegranskat)abstract
    • We will demonstrate that ultrasonic treatment of a graphite crystal in water can lead to the formation of small graphene-like flakes in solution. The delamination of the graphite can be increased dramatically by intercalation of bromine from a Br2-saturated water solution. After ultrasonic treatment, large amounts of graphene-like flakes with varying thickness are observed in SEM and TEM. They can be adsorbed onto a surface of a suitable substrate by a simple dipping technique. The effect of polar and non-polar solvents as well as adsorption of the graphene on hydrophobic and hydrophilic substrates will be demonstrated and compared. DFT calculations of the intercalation process have been carried out using the SIESTA package and the effect of bromine intercalation on cohesive energy and electronic structure will be discussed and compared with experimental data. Finally, the general approach of using ultrasonic treatment and intercalation as a facile route to graphene synthesis compared to other methods will be discussed.
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