| 1. |
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Solmi, M, et al.
(författare)
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- 2022
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Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 10. |
- Ahmed, A., et al.
(författare)
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Highly efficient composite electrolyte for natural gas fed fuel cell
- 2016
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Ingår i: International journal of hydrogen energy. - : Elsevier. - 0360-3199 .- 1879-3487. ; 41:16, s. 6972-6979
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Tidskriftsartikel (refereegranskat)abstract
- Solid oxide fuel cells (SOFCs) have the ability to operate with different variants of hydro carbon fuel such as biogas, natural gas, methane, ethane, syngas, methanol, ethanol, hydrogen and any other hydrogen rich gas. Utilization of these fuels in SOFC, especially the natural gas, would significantly reduce operating cost and would enhance the viability for commercialization of FC technology. In this paper, the performance of two indigenously manufactured nanocomposite electrolytes; barium and samarium doped ceria (BSDC-carbonate); and lanthanum and samarium doped ceria (co-precipitation method LSDC-carbonate) using natural gas as fuel is discussed. The nanocomposite electrolytes were synthesized using co-precipitation and wet chemical methods (here after referred to as nano electrolytes). The structure and morphology of the nano electrolytes were examined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The fuel cell performance (OCV) was tested at temperature (300-600 °C). The ionic conductivity of the nano electrolytes were measured by two probe DC method. The detailed composition analysis of nano electrolytes was performed with the help of Raman Spectroscopy. Electrochemical study has shown an ionic conductivity of 0.16 Scm-1 at 600 °C for BSDC-carbonate in hydrogen atmosphere, which is higher than conventional electrolytes SDC and GDC under same conditions. In this article reasonably good ionic conductivity of BSDC-carbonate, at 600 °C, has also been achieved in air atmosphere which is comparatively greater than the conventional SDC and GDC electrolytes.
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| 11. |
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| 12. |
- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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| 13. |
- Hassanin, Abdallah A., et al.
(författare)
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Emergence, evolution, and vaccine production approaches of SARS-CoV-2 virus : benefits of getting vaccinated and common questions
- 2022
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Ingår i: Saudi Journal of Biological Sciences. - : Elsevier. - 1319-562X. ; 29:4, s. 1981-1997
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Forskningsöversikt (refereegranskat)abstract
- The emergence of coronavirus disease 2019 (COVID-19) pandemic in Wuhan city, China at the end of 2019 made it urgent to identify the origin of the causal pathogen and its molecular evolution, to appropriately design an effective vaccine. This study analyzes the evolutionary background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS-2) in accordance with its close relative SARS-CoV (SARS-1), which was emerged in 2002. A comparative genomic and proteomic study was conducted on SARS-2, SARS-1, and Middle East respiratory syndrome coronavirus (MERS), which was emerged in 2012. In silico analysis inferred the genetic variability among the tested viruses. The SARS-1 genome harbored 11 genes encoding 12 proteins, while SARS-2 genome contained only 10 genes encoding for 10 proteins. MERS genome contained 11 genes encoding 11 proteins. The analysis also revealed a slight variation in the whole genome size of SARS-2 comparing to its siblings resulting from sequential insertions and deletions (indels) throughout the viral genome particularly ORF1AB, spike, ORF10 and ORF8. The effective indels were observed in the gene encoding the spike protein that is responsible for viral attachment to the angiotensin-converting enzyme 2 (ACE2) cell receptor and initiating infection. These indels are responsible for the newly emerging COVID-19 variants αCoV, βCoV, γCoV and δCoV. Nowadays, few effective COVID-19 vaccines developed based on spike (S) glycoprotein were approved and become available worldwide. Currently available vaccines can relatively prevent the spread of COVID-19 and suppress the disease. The traditional (killed or attenuated virus vaccine and antibody-based vaccine) and innovated vaccine production technologies (RNA- and DNA-based vaccines and viral vectors) are summarized in this review. We finally highlight the most common questions related to COVID-19 disease and the benefits of getting vaccinated.
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| 14. |
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| 15. |
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| 16. |
- Stoop, Thomas F., et al.
(författare)
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Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy
- 2024
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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| 17. |
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| 18. |
- Cheema, H. A., et al.
(författare)
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In-hospital mortality of COVID-19 patients hospitalized with ST-segment elevation myocardial infarction : A meta-analysis
- 2022
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Ingår i: IJC Heart & Vasculature. - : Elsevier BV. - 2352-9067. ; 43
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Coronavirus Disease 2019 (COVID-19) has been associated with an increased risk of adverse cardiovascular events including arteriovenous thrombosis, myocarditis and acute myocardial injury. Relevant literature to date has reported widely varying estimates of mortality, ranging from approximately 2 to 11 times higher odds of mortality in COVID-19-positive STEMI (ST-segment elevation myocardial infarction) patients. Hence, we conducted this meta-analysis to resolve these inconsistencies and assess the impact of COVID-19 infection on mortality and other clinical outcomes in patients presenting with STEMI. Methods: This meta-analysis was registered in PROSPERO (CRD42021297458) and performed according to the Cochrane Handbook for Systematic Reviews of Interventions. PubMed and Embase were searched from inception to November 2021 (updated on April 2022) using a search strategy consisting of terms relating to COVID-19, STEMI, and mortality. Results: We identified 435 studies through our initial search. After screening according to our eligibility criteria, a total of 11 studies were included. Compared with the non-COVID-19 STEMI patients, the in-hospital mortality rate was higher in COVID-19-positive STEMI patients. Similarly, the risk of cardiogenic shock was higher in the COVID-19-positive patients. Length of hospital stay was longer in STEMI patients with COVID-19. Conclusions: Our study highlights the necessity for early evaluation of COVID-19 status in all STEMI patients followed by risk stratification, prompt reperfusion and more aggressive management of COVID-19-positive patients. Further research is needed to elucidate the mechanisms behind poorer prognosis in such patients.
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| 19. |
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| 20. |
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| 21. |
- Javed, A., et al.
(författare)
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Study of Effect of Superstrate on Wideband Array Antenna
- 2019
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Ingår i: RAEE 2019 - International Symposium on Recent Advances in Electrical Engineering. - : Institute of Electrical and Electronics Engineers Inc.. - 9781728130729
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Konferensbidrag (refereegranskat)abstract
- This article presents a twelve-element based wideband microstrip linear array antenna. In the array design, the elements are studded with stubs to enhance the bandwidth. Resonances are achieved in the broader band by introducing the slotted ground. The design is equipped with superstrate at a specific distance from the array antenna to improve the gain and efficiency. The proposed work has a good percentage bandwidth of 43.28% with stable radiation characteristics. The introduction of superstrate causes the proposed structure to enhance its peak gain to 7.6 dBi and the efficiency to 77%. The presented array covers the high-frequency spectrum from 24.343 GHz to 37.79 GHz, thus making it a good choice for millimeter wave applications.
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| 22. |
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| 23. |
- Kantarelis, Efthymios, PhD, 1982-, et al.
(författare)
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Engineering the Catalytic Properties of HZSM5 by Cobalt Modification and Post-synthetic Hierarchical Porosity Development
- 2019
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Ingår i: Topics in catalysis. - : Springer Science and Business Media LLC. - 1022-5528 .- 1572-9028. ; 62:7, s. 773-785
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Tidskriftsartikel (refereegranskat)abstract
- Hierarchical zeolites have been identified as special catalytic materials with improved catalytic properties. In this study, hierarchical bifunctional ZSM5 based catalysts were prepared by desilication for controlled mesoporosity development and have been modified by Co doping. Their performance in the catalytic pyrolysis of oak in a lab scale reactor was evaluated. Desilicated counterparts were proven more active in deoxygenation of bio oil, while carbon deposition on the catalysts reduced compared to non-desilicated counterparts. Increased Lewis acidity favors decarboxylation reactions, while higher olefins as well as PAH content indicate easier diffusion within and from the porous network and interactions in the mesopores. The conversion of bulky lignin molecules (alkoxy phenols) is enhanced by the mesopores, while acidity is of secondary importance. Coke deposition inside the pores is more profound in the desilicated catalysts due to larger pore size. Carbon deposition on the catalysts is reduced in the following order: HZSM5 > Co/HZSM5 > Ds-HZSM5 > Co/Ds-HZSM5. GC–MS characterization of the CH2Cl2 soluble coke indicated that for the desilicated counterparts the main coke precursors are the bulky lignin molecules which are partially deoxygenated.
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| 24. |
- Khan, Muhammad Shahzeb, et al.
(författare)
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Leveraging electronic health records to streamline the conduct of cardiovascular clinical trials
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1890-1909
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Forskningsöversikt (refereegranskat)abstract
- Conventional randomized controlled trials (RCTs) can be expensive, time intensive, and complex to conduct. Trial recruitment, participation, and data collection can burden participants and research personnel. In the past two decades, there have been rapid technological advances and an exponential growth in digitized healthcare data. Embedding RCTs, including cardiovascular outcome trials, into electronic health record systems or registries may streamline screening, consent, randomization, follow-up visits, and outcome adjudication. Moreover, wearable sensors (i.e. health and fitness trackers) provide an opportunity to collect data on cardiovascular health and risk factors in unprecedented detail and scale, while growing internet connectivity supports the collection of patient-reported outcomes. There is a pressing need to develop robust mechanisms that facilitate data capture from diverse databases and guidance to standardize data definitions. Importantly, the data collection infrastructure should be reusable to support multiple cardiovascular RCTs over time. Systems, processes, and policies will need to have sufficient flexibility to allow interoperability between different sources of data acquisition. Clinical research guidelines, ethics oversight, and regulatory requirements also need to evolve. This review highlights recent progress towards the use of routinely generated data to conduct RCTs and discusses potential solutions for ongoing barriers. There is a particular focus on methods to utilize routinely generated data for trials while complying with regional data protection laws. The discussion is supported with examples of cardiovascular outcome trials that have successfully leveraged the electronic health record, web-enabled devices or administrative databases to conduct randomized trials.
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| 25. |
- Maisel, Alan, et al.
(författare)
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Effect of Spironolactone on 30-Day Death and Heart Failure Rehospitalization (from the COACH Study)
- 2014
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 114:5, s. 737-742
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Tidskriftsartikel (refereegranskat)abstract
- The aim of our study is to investigate the effect of spironolactone on 30-day outcomes in patients with acute heart failure (AHF) and the association between treatment and outcomes stratified by biomarkers. We conducted a secondary analysis of the biomarker substudy of the multicenter COACH (Co-ordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) trial involving 534 AHF patients for 30-day mortality and HF rehospitalizations. Spironolactone therapy was initiated and terminated at the discretion of the treating physician; 30-day outcomes were compared between patients who were treated with spironolactone and those who were not. Outcomes with spironolactone therapy. were explored based on N-terminal pro-B-type natriuretic peptide, ST2, galectin-3, and creatinine levels. Spironolactone was prescribed to 297 (55.6%) patients at discharge (158 new and 139 continued). There were 19 deaths and 30 HF rehospitalizations among 46 patients by 30 days. Patients discharged on spironolactone had significantly less 30-day event (hazard ratio 0.538, p = 0.039) after adjustment for multiple risk factors. Initiation of spironolactone in patients who were not on spironolactone before admission was associated with a significant reduction in event rate (hazard ratio 0.362, p = 0.027). The survival benefit of spironolactone was more prominent in patient groups with elevations of creatinine, N-terminal pro B-type natriuretic peptide, ST2, or galectin-3. In conclusion, AHF patients who received spironolactone during hospitalization had significantly fewer 30-day mortality and HF rehospitalizations, especially in high-risk patients.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Raza, Rizwan, et al.
(författare)
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Composite electrolyte with proton conductivity for low-temperature solid oxide fuel cell
- 2015
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Ingår i: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 107:18
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Tidskriftsartikel (refereegranskat)abstract
- In the present work, cost-effective nanocomposite electrolyte (Ba-SDC) oxide is developed for efficient low-temperature solid oxide fuel cells (LTSOFCs). Analysis has shown that dual phase conduction of O-2 (oxygen ions) and H+ (protons) plays a significant role in the development of advanced LTSOFCs. Comparatively high proton ion conductivity (0.19 s/cm) for LTSOFCs was achieved at low temperature (460°C). In this article, the ionic conduction behaviour of LTSOFCs is explained by carrying out electrochemical impedance spectroscopy measurements. Further, the phase and structure analysis are investigated by X-ray diffraction and scanning electron microscopy techniques. Finally, we achieved an ionic transport number of the composite electrolyte for LTSOFCs as high as 0.95 and energy and power density of 90% and 550 mW/cm2, respectively, after sintering the composite electrolyte at 800°C for 4 h, which is promising. Our current effort toward the development of an efficient, green, low-temperature solid oxide fuel cell with the incorporation of high proton conductivity composite electrolyte may open frontiers in the fields of energy and fuel cell technology.
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| 31. |
- Raza, Rizwan, et al.
(författare)
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Fuel cell technology for sustainable development in Pakistan - An over-view
- 2016
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Ingår i: Renewable & sustainable energy reviews. - : Elsevier. - 1364-0321 .- 1879-0690. ; 53, s. 450-461
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Tidskriftsartikel (refereegranskat)abstract
- Fuel cell technology holds the combination of benefits, which are barely offered by any other energy generating technology. Because the fuel used in this technology is found in abundance in nature and can also be renewed/sustained. Pakistan is blessed with renewable energy resources which are suitable for fuel cell technology. Therefore, fuel cell technology offers a great opportunity to meet the demand of energy and for the sustainable development of Pakistan. The energy research group at COMSATS Institute of Information Technology (CIIT), Lahore has made efforts to study the technical aspects of fuel cell technology and its commercial benefits. The research group is interested in finding ways and means of generating and storing the energy produced by using fuel cells. In this paper, the research activities on fuel cell technology in Pakistan have been reviewed and it is also discussed how this technology can resolve the current energy crises in Pakistan and can be the source of sustainable energy. It has been also reviewed that the country would greatly benefit from fuel cells and fuel cell hybrid system (environmental friendly technology), which could be the best solution for electricity production as well for automobile industry.
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| 32. |
- Smith, Gustav, et al.
(författare)
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Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure
- 2016
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
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| 33. |
- Ulfat, Intikhab, 1966, et al.
(författare)
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Estimation of solar energy potential for Islamabad, Pakistan
- 2012
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Ingår i: Energy Procedia. - : Elsevier. - 1876-6102. ; 18, s. 1496-1500
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Konferensbidrag (refereegranskat)abstract
- In order to design a solar energy system with optimized performance a thorough knowledge of solar radiation data for a considerably long period (20-25 years) is a pre-requisite. For developing countries like Pakistan, the need of empirical models to assess the feasibility of solar energy utilization seems inevitable due to the absence and scarcity of trustworthy solar radiation data. We present such models for the capital city of Pakistan, Islamabad to estimate global and diffuse solar radiation. It is found that with the exception of monsoon month, solar energy can be utilized very efficiently throughout the year. The models suggested could be used for most of the north-eastern areas of Pakistan, which are similar to Islamabad with respect to the climate and the availability of solar radiation but lack in the record of solar radiation data.
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| 34. |
- Usman, Muhammad Shariq, et al.
(författare)
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The need for increased pragmatism in cardiovascular clinical trials
- 2022
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Ingår i: Nature Reviews Cardiology. - : Springer Nature. - 1759-5002 .- 1759-5010. ; 19:11, s. 737-750
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Tidskriftsartikel (refereegranskat)abstract
- The majority of cardiovascular randomized controlled trials (RCTs) test interventions in selected patient populations under explicitly protocol-defined settings. Although these 'explanatory' trial designs optimize conditions to test the efficacy and safety of an intervention, they limit the generalizability of trial findings in broader clinical settings. The concept of 'pragmatism' in RCTs addresses this concern by providing counterbalance to the more idealized situation underpinning explanatory RCTs and optimizing effectiveness over efficacy. The central tenets of pragmatism in RCTs are to test interventions in routine clinical settings, with patients who are representative of broad clinical practice, and to reduce the burden on investigators and participants by minimizing the number of trial visits and the intensity of trial-based testing. Pragmatic evaluation of interventions is particularly important in cardiovascular diseases, where the risk of death among patients has remained fairly stable over the past few decades despite the development of new therapeutic interventions. Pragmatic RCTs can help to reveal the 'real-world' effectiveness of therapeutic interventions and elucidate barriers to their implementation. In this Review, we discuss the attributes of pragmatism in RCT design, conduct and interpretation as well as the general need for increased pragmatism in cardiovascular RCTs. We also summarize current challenges and potential solutions to the implementation of pragmatism in RCTs and highlight selected ongoing and completed cardiovascular RCTs with pragmatic trial designs.
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| 35. |
- Vaduganathan, Muthiah, et al.
(författare)
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Dronedarone for the treatment of atrial fibrillation with concomitant heart failure with preserved and mildly reduced ejection fraction : a post-hoc analysis of the ATHENA trial
- 2022
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:6, s. 1094-1101
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Limited therapeutic options are available for the management of atrial fibrillation/flutter (AF/AFL) with concomitant heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF). Dronedarone reduces the risk of cardiovascular events in patients with AF, but sparse data are available examining its role in patients with AF complicated by HFpEF and HFmrEF. Methods and results: ATHENA was an international, multicentre trial that randomized 4628 patients with paroxysmal or persistent AF/AFL and cardiovascular risk factors to dronedarone 400 mg twice daily versus placebo. We evaluated patients with (i) symptomatic HFpEF and HFmrEF (defined as left ventricular ejection fraction [LVEF] >40%, evidence of structural heart disease, and New York Heart Association class II/III or diuretic use), (ii) HF with reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVEF ≤40%), and (iii) those without HF. We assessed effects of dronedarone versus placebo on death or cardiovascular hospitalization (primary endpoint), other key efficacy endpoints, and safety. Overall, 534 (12%) had HFpEF or HFmrEF, 422 (9%) had HFrEF or left ventricular dysfunction, and 3672 (79%) did not have HF. Patients with HFpEF and HFmrEF had a mean age of 73 ± 9 years, 37% were women, and had a mean LVEF of 57 ± 9%. Over a mean follow-up of 21 ± 5 months, dronedarone consistently reduced risk of death or cardiovascular hospitalization (hazard ratio 0.76; 95% confidence interval 0.69–0.84) without heterogeneity based on HF status (pinteraction >0.10). This risk reduction in the primary endpoint was consistent across the range of LVEF (as a continuous function) in HF without heterogeneity (pinteraction = 0.71). Rates of death, cardiovascular hospitalization, and HF hospitalization each directionally favoured dronedarone versus placebo in HFpEF and HFmrEF, but these treatment effects were not statistically significant in this subgroup. Conclusions: Dronedarone is associated with reduced cardiovascular events in patients with paroxysmal or persistent AF/AFL and HF across the spectrum of LVEF, including among those with HFpEF and HFmrEF. These data support a rationale for a future dedicated and powered clinical trial to affirm the net clinical benefit of dronedarone in this population.
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| 36. |
- Armstrong, Paul W, et al.
(författare)
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Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:20, s. 1883-1893
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure.RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30).CONCLUSIONS: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received placebo. (Funded by Merck Sharp & Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).
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| 37. |
- Beier, Richard A., et al.
(författare)
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Validation of borehole heat exchanger models against multi-flow rate thermal response tests
- 2018
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Ingår i: Geothermics. - : Elsevier BV. - 0375-6505. ; 71, s. 55-68
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Tidskriftsartikel (refereegranskat)abstract
- A recently developed vertical borehole ground heat exchanger model that accounts for transit time effects and time-varying short-circuiting heat transfer has been validated against two multi-flow-rate thermal response tests (MFR-TRT). The MFR-TRT, when performed with a wide range of flow rates, results in significant changes in the borehole thermal resistance, the borehole internal thermal resistance, and the short-circuiting heat transfer between the two legs of a single U-tube. The model accounts for short-circuiting by an analytically computed weighting factor that is used to determine the mean fluid temperature. The weighting factor portion of the model can be readily utilized in other ground heat exchanger models that currently rely on a simple mean fluid temperature. Use of the weighting factor is shown to give significantly better estimations of entering and exiting fluid temperature than using the simple mean fluid temperature. The new model is also compared to an alternative approach using an effective borehole thermal resistance. While both the effective borehole thermal resistance model and the weighting factor give quite good results a few hours after a step change in flow rate, the weighting factor model gives much better results in the first few hours after a step change in flow rate.
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| 38. |
- Bournas, Iason, et al.
(författare)
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Energy renovation of an office building using a holistic design approach
- 2016
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Ingår i: Journal of Building Engineering. - : Elsevier BV. - 2352-7102. ; 7:September 2016, s. 194-206
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a holistic approach to perform energy renovations of office buildings. A real case study is used to demonstrate how different software can be used to facilitate the work of architects and engineers during different design stages. Initially, the moisture safety of the building is coupled to its energy performance to define the optimum insulation level. The new interior layout is based on an initial daylight study, rather than on architectural intuition. On a second stage, shading and natural ventilation are studied to eradicate any cooling demand, while the interdependence between heating energy and daylight is assessed for the use of light-wells. To demonstrate the trade-offs between visual control and electrical lighting, different shading systems are examined for a cellular office. Finally, two alternate HVAC systems are analyzed to investigate whether passive standards can be achieved with an all-air system and/or a hydronic system.
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| 39. |
- Goodwin, Nathan P., et al.
(författare)
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Morbidity and Mortality Associated With Heart Failure in Acute Coronary Syndrome : A Pooled Analysis of 4 Clinical Trials
- 2023
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Ingår i: Journal of Cardiac Failure. - : Elsevier. - 1071-9164 .- 1532-8414. ; 29:12, s. 1603-1614
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) may complicate acute coronary syndrome (ACS) and is associ-ated with a high burden of short-and long-term morbidity and mortality. Only limited data regarding future ischemic events and rehospitalization are available for patients who suffer HF before or during ACS.Methods: A secondary analysis of 4 large ACS trials (PLATO, APPRAISE-2, TRACER, and TRIL-OGY ACS) using Cox proportional hazards models was performed to investigate the associa-tion of HF status (no HF, chronic HF, de novo HF) at presentation for ACS with all-cause and cardiovascular death, major adverse cardiovascular event (MACE ), myocardial infarction, stroke, and hospitalization for heart failure (HHF) by 1 year. Cumulative incidence plots are presented at 30 days and 1 year.Results: A total of 11.1% of the 47,474 patients presenting with ACS presented with evidence of acute HF, 55.0% of whom presented with de novo HF. Patients with chronic HF presented with evidence of acute HF at a higher rate than those with no previous HF (40.3% vs 6.9%). Compared to those without HF, those with chronic and de novo HF had higher rates of all-cause mortality (adjusted hazard ratio [aHR] 2.01, 95% confidence interval [CI] 1.72-2.34 and aHR 1.47, 95% CI1.15-1.88, respectively), MACE (aHR 1.47, 95% CI1.31-1-.66 and aHR 1.38, 95% CI1.12-1.69), and HHF (aHR 2.29, 95% CI2.02-2.61 and aHR 1.48, 95% CI 1.20-1.82) at 1 year.Conclusion: In this large cohort of patients with ACS, both prior and de novo HF complicating ACS were associated with significantly higher risk-adjusted rates of death, ischemic events and HHF at 30 days and 1 year. Further studies examining the association between HF and out-comes in this high-risk population are warranted, especially given the advent of more contem-porary HF therapies.
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| 40. |
- Guezgouz, M., et al.
(författare)
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Optimal hybrid pumped hydro-battery storage scheme for off-grid renewable energy systems
- 2019
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Ingår i: Energy Conversion and Management. - : Elsevier Ltd. - 0196-8904 .- 1879-2227. ; 199
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Tidskriftsartikel (refereegranskat)abstract
- The development of energy storage systems paves the way towards a high integration of renewable energy sources in the electricity generation sector. Considering above, this paper introduces a new energy management strategy to efficiently coordinate a hybrid energy storage system based on pumped hydro storage (long term bulk storage) with batteries (short term, more flexible). For the purpose of this analysis, hourly time series of irradiation, wind speed, temperature and real measured load (characteristic for farmstead) covering one year were gathered for the selected site in Algeria. The optimal size of the system is determined based on a multi-objective optimization using a grey wolf optimizer implemented in MATLAB software. The results indicate that the hybrid storage system enables achieving higher reliability at lower cost in comparison to a system with single storage technology. The use of hybrid storage also reduces the curtailment of renewable generation. Further findings reveal that the cost of an optimal energy supply system with 97.5% reliability is 0.162 €/kWh, 0.207 €/kWh and 1.462 €/kWh for hybrid storage, battery and pumped storage, respectively. However, sensitivity analysis shows that the optimal hybrid storage configuration is less resilient when changes in irradiation/temperature/load are considered. This indicates that special actions (upscale of installed power) must be undertaken to avoid lower performance of hybrid storage systems. In summary, the hybrid storage system seems to be better sized for consideration in optimized solar/wind conditions, but by avoiding oversizing they are less resilient to future potential changes in renewable energy availability.
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| 41. |
- Harrington, Josephine, et al.
(författare)
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Acute Decompensated Heart Failure in the Setting of Acute Coronary Syndrome
- 2022
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Ingår i: JACC. Heart failure. - : Elsevier. - 2213-1779 .- 2213-1787. ; 10:6, s. 404-414
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Forskningsöversikt (refereegranskat)abstract
- Acute coronary syndrome (ACS) is frequently complicated by evidence of heart failure (HF). Those at highest risk for acute decompensated HF in the setting of ACS (ACS-HF) are older, female, and have preexisting heart disease, type 2 diabetes mellitus, hypertension, and/or kidney disease. The presence of ACS-HF is strongly associated with higher mortality and more frequent readmissions, especially for HF. Low implementation of guideline-directed medical therapy has further complicated the clinical care of this high-risk population. Improved utilization of current therapies, coupled with further investigation of strategies to manage ACS-HF, is desperately needed to improve outcomes in this vulnerable population, and the results of currently ongoing or recently concluded ACS-HF studies in this population are of great interest. In this review, we explore the pathophysiology, epidemiology, risk factors, and outcomes for patients with ACS-HF, and describe both existing evidence for management of this challenging condition and areas requiring further research. (J Am Coll Cardiol HF 2022;10:404-414) (c) 2022 by the American College of Cardiology Foundation.
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| 42. |
- Imran, Z, et al.
(författare)
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Fabrication of cadmium titanate nanofibers via electrospinning technique
- 2012
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Ingår i: Ceramics International. - : Elsevier. - 0272-8842 .- 1873-3956. ; 38:4, s. 3361-3365
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Tidskriftsartikel (refereegranskat)abstract
- Here we present an electrospinning technique for the fabrication of cadmium titanate/polyvinyl-pyrrolidone composite nanofibers. The composite nanofibers are then annealed at 600 degrees C to obtain ilmenite rhombohedral phase cadmium titanate nanofibers. The structure, composition, thermal stability and optical properties of as synthesized and annealed cadmium titanate nanofibers are characterized by X-ray diffraction, energy dispersive X-ray spectroscopy, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy. The average diameter and length of the nanofibers are found to be similar to 150-200 nm and similar to 100 mu m, respectively.
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| 43. |
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| 44. |
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| 45. |
- Javed, Muhammad Ahsan, et al.
(författare)
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Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe
- 2019
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 19:1, s. 97-104
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors.RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis.CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.
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| 46. |
- Javed, Muhammad Atif, et al.
(författare)
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Towards variant management and change impact analysis in safety-oriented process-product lines
- 2019
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Ingår i: Proceedings of the ACM Symposium on Applied Computing. - New York, NY, USA : Association for Computing Machinery. ; , s. 2372-2375
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Konferensbidrag (refereegranskat)abstract
- In safety-critical (software) systems, safety management embraces both processes and products, which due to e.g., product's upgrade, tend to be tailored, giving rise to safety-oriented product lines and corresponding safety-oriented process lines. To tailor these lines systematically, their inter-dependencies would have been taken into consideration. To date, however, no satisfying implemented solution is available on the shelf. Accordingly, this paper focuses on the co-engineering of process and product lines. At first, the process and product lines need to be established for which the integration between Eclipse Process Framework (EPF) Composer, Composition with Guarantees for High-integrity Embedded Software Components Assembly (CHESS) Tool and Base Variability Resolution (BVR) Tool is achieved; they are process engineering, product design and variant management solutions, respectively. After that, the process and product lines are integrated. This is done for cross-dimension variant management and change impact analysis. The applicability of the integrated lines is illustrated for the attitude and orbit control subsystem.
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| 47. |
- Javed, Muhammad Shahzad, et al.
(författare)
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Impact of multi-annual renewable energy variability on the optimal sizing of off-grid systems
- 2023
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Ingår i: Renewable & sustainable energy reviews. - : Elsevier Ltd. - 1364-0321 .- 1879-0690. ; 183
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Tidskriftsartikel (refereegranskat)abstract
- It remains a significant technical and economic challenge to fully power large-scale grids with intermittent renewable energy (RE). Meanwhile, due to the rapid decrease in the cost of RE power generation technologies in recent years, the number of real-world implementations and studies dedicated to the optimal capacity sizing of renewable off-grid systems has increased. However, a common approach in the literature is to rely on typical single-year meteorological and demand data. A negative effect of this assumption is that it does not consider the RE inter-annual variability, which might cause blackouts or oversizing the system and large curtailments. This study employs 43 years of hourly solar, wind, and demand data, coupled with different microgrid configurations, to evaluate the impact of diverse simulation periods on the total system cost, optimal RE mix, and system reliability. Our findings indicate that extended simulation periods considerably increased renewable energy systems (RES) reliability and that the resulting configurations can be up to 94% more robust than those obtained using a single year of data. Additionally, the optimal energy storage requirements increased when considering longer simulation periods, indicating that short simulation periods could underestimate energy storage capacities in off-grid systems. The overestimations or underestimations resulting from optimizations based on single-year data directly affect the long-term sustainability, reliability, and cost-effectiveness of the RES.
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| 48. |
- Ke, PC, et al.
(författare)
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Mitigation of Amyloidosis with Nanomaterials
- 2020
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Ingår i: Advanced materials (Deerfield Beach, Fla.). - : Wiley. - 1521-4095 .- 0935-9648. ; 32:18, s. e1901690-
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Tidskriftsartikel (refereegranskat)
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| 49. |
- Le, Nha, et al.
(författare)
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Real-world clinical practice of intensified chemotherapies for metastatic pancreatic cancer : results from a Pan-European questionnaire study
- 2016
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Ingår i: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 94:4, s. 222-229
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Recently, FOLFIRINOX and gemcitabine + nab-paclitaxel have been introduced as a novel intensified chemotherapy regimen for patients with metastasized pancreatic cancer. This study aims to analyze the real-world clinical practice with FOLFIRINOX and gemcitabine + nab-paclitaxel across Europe.Methods: Invitations to participate in an anonymous web-based questionnaire were sent via e-mail to 5,420 doctors in 19 European countries through the network of national gastroenterological, oncological, surgical and pancreatic societies as well as the European Pancreatic Club. The questionnaire consisted of 20 questions, 14 regarding the use of intensified chemotherapy, 4 regarding demographics of the participants, and 1 to verify the active involvement in the management of metastatic pancreatic cancer.Results: Two hundred and thirteen responses were received and 153 entries were valid for analysis. Of those, 63.4% came from an academic institution, 51% were oncologists, and 52% treated more than 25 cases per year. A majority of responses (71%) were from Italy (40%), Germany (23%), and Spain (8%). As first-line therapy, 11% used gemcitabine +/- erlotinib, 42% used FOLFIRINOX, and 47% used gemcitabine + nab-paclitaxel. Of the intensified regimens, both were applied to equal parts, but the likelihood of protocol deviation was higher when using FOLFIRINOX (p < 0.01). FOLFIRINOX was considered more toxic than gemcitabine + nab-paclitaxel (neutropenia 88 vs. 68%; polyneuropathy 42 vs. 41%; rapid deterioration 42 vs. 31%). FOLFIRINOX was rated to achieve longer survival with an acceptable quality of life (52 vs. 44%). Moreover, 57% of participants thought that gemcitabine + nab-paclitaxel should be the backbone for further clinical trials in pancreatic cancer.Conclusion: Intensified chemotherapy is widely used in pancreatic cancer patients in Europe following its recent clinical approval. Interestingly, nab-paclitaxel and FOLFIRINOX were used at comparable frequency although the latter had to be de-escalated more often.
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| 50. |
- Maggino, Laura, et al.
(författare)
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Reappraisal of a 2-Cm Cut-off Size for the Management of Cystic Pancreatic Neuroendocrine Neoplasms : A Multicenter International Study
- 2021
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 273:5, s. 973-981
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to characterize an international cohort of resected cystic pancreatic neuroendocrine neoplasms (cPanNENs) and identify preoperative predictors of aggressive behavior.BACKGROUND: The characteristics of cPanNENs are unknown and their clinical management remains unclear. An observational strategy for asymptomatic cPanNENs ≤2 cm has been proposed by recent guidelines, but evidence is scarce and limited to single-institutional series.METHODS: Resected cPanNENs (1995-2017) from 16 institutions worldwide were included. Solid lesions (>50% solid component), functional tumors, and MEN-1 patients were excluded. Aggressiveness was defined as lymph node (LN) involvement, G3 grading, distant metastases, and/or recurrence.RESULTS: Overall, 263 resected cPanNENs were included, among which 177 (63.5%) were >2 cm preoperatively. A preoperative diagnosis of cPanNEN was established in 162 cases (61.6%) and was more frequent when patients underwent endoscopic ultrasound [EUS, odds ratio (OR) 2.69, 95% confidence interval (CI) 1.52-4.77] and somatostatin-receptor imaging (OR 3.681, 95% CI 1.809-7.490), and for those managed in specialized institutions (OR 3.12, 95% CI 1.57-6.21). Forty-one cPanNENs (15.6%) were considered aggressive. In the whole cohort, LN involvement on imaging, age >65 years, preoperative size >2 cm, and pancreatic duct dilation were independently associated with aggressive behavior. In asymptomatic patients, older age and a preoperative size >2 cm remained independently associated with aggressiveness. Only 1 of 61 asymptomatic cPanNENs ≤2 cm displayed an aggressive behavior.CONCLUSIONS: The diagnostic accuracy of cPanNENs is increased by the use of EUS and somatostatin-receptor imaging and is higher in specialized institutions. Preoperative size >2 cm is independently associated with aggressive behavior. Consequently, a watch-and-wait policy for sporadic asymptomatic cPanNENs ≤2 cm seems justified and safe for most patients.
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