| 1. |
- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 2. |
- Axfors, Cathrine, et al.
(author)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Research review (peer-reviewed)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 3. |
- Wang, Li-San, et al.
(author)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Journal article (peer-reviewed)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 4. |
- Bogachuk, Dmitry, et al.
(author)
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Perovskite Solar Cells with Carbon-Based Electrodes - Quantification of Losses and Strategies to Overcome Them
- 2022
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In: Advanced Energy Materials. - : John Wiley & Sons. - 1614-6832 .- 1614-6840. ; 12:10
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Journal article (peer-reviewed)abstract
- Carbon-based electrodes represent a promising approach to improve stability and up-scalability of perovskite photovoltaics. The temperature at which these contacts are processed defines the absorber grain size of the perovskite solar cell: in cells with low-temperature carbon-based electrodes (L-CPSCs), layer-by-layer deposition is possible, allowing perovskite crystals to be large (>100 nm), while in cells with high-temperature carbon-based contacts (H-CPSCs), crystals are constrained to 10-20 nm in size. To enhance the power conversion efficiency of these devices, the main loss mechanisms are identified for both systems. Measurements of charge carrier lifetime, quasi-Fermi level splitting (QFLS) and light-intensity-dependent behavior, supported by numerical simulations, clearly demonstrate that H-CPSCs strongly suffer from non-radiative losses in the perovskite absorber, primarily due to numerous grain boundaries. In contrast, large crystals of L-CPSCs provide a long carrier lifetime (1.8 mu s) and exceptionally high QFLS of 1.21 eV for an absorber bandgap of 1.6 eV. These favorable characteristics explain the remarkable open-circuit voltage of over 1.1 V in hole-selective layer-free L-CPSCs. However, the low photon absorption and poor charge transport in these cells limit their potential. Finally, effective strategies are provided to reduce non-radiative losses in H-CPSCs, transport losses in L-CPSCs, and to improve photon management in both cell types.
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| 5. |
- Woll, Petter S, et al.
(author)
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Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo.
- 2014
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In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 25:6, s. 794-808
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Journal article (peer-reviewed)abstract
- Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation.
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| 6. |
- Bowen, David E., et al.
(author)
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Learning from the pioneering founders of the service research field
- 2023
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In: Journal of Service Management. - : Emerald Group Publishing Limited. - 1757-5818 .- 1757-5826. ; 34:4, s. 605-630
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Journal article (peer-reviewed)abstract
- Purpose: A small group of pioneering founders led the creation and early evolution of the service research field. Decades later, this article shares timeless service wisdom from ten of those pioneering founders. Design/methodology/approach: Bowen and Fisk specified three criteria by which to identify a pioneering founder. In total, 11 founders met the criteria (Bateson, Berry, Bitner, Brown, Chase, Edvardsson, Grönroos, Gummesson, Parasuraman, Schneider and Zeithaml) and were invited to join Bowen and Fisk – founders that also met the criteria as coauthors. Ten founders then answered a set of questions regarding their careers as service scholars and the state of the field. Findings: Insightful reflections were provided by each of the ten pioneering founders. In addition, based on their synthesis of the reflections, Bowen and Fisk developed nine wisdom themes for service researchers to consider and to possibly act upon. Originality/value: The service research field is in its fifth decade. This article offers a unique way to learn directly from the pioneering founders about the still-relevant history of the field, the founders’ lives and contributions as service scholars and the founders’ hopes and concerns for the service research field.
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| 7. |
- Durrant, Abigail C., et al.
(author)
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Problems in Practice: Understanding Design Research by Critiquing Cases
- 2017
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In: CHI EA '17 Proceedings of the 2016 CHI Conference Extended Abstracts on Human Factors in Computing Systems Pages 636-643. - : ACM. - 9781450346566
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Conference paper (peer-reviewed)abstract
- Responding to challenges to better understand design research practice, its contributions to knowledge production and its value to HCI, our one-day workshop critically reflects on case examples of design research practice in interdisciplinary HCI projects. We invite position papers that offer personal perspectives on "critical incidents" in such projects, specifically focusing on problems, miscommunications, tensions and failures. We establish a supportive, discursive forum for constructive critical reflection, to deepen understanding about the nature and value of design practice as a form of research inquiry within HCI. The workshop also aims to develop conceptual resources for supporting design practice in interdisciplinary research.
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| 8. |
- Giagounidis, Aristoteles, et al.
(author)
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Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study
- 2014
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 93:5, s. 429-438
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Journal article (peer-reviewed)abstract
- ObjectiveA subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). MethodsPatients received lenalidomide 10mg/d (days 1-21; n=47) or 5mg/d (days 1-28; n=43) on 28-d cycles or placebo (n=45). From the placebo and lenalidomide 5mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10mg at 16wk, respectively. ResultsRates of red blood cell-transfusion independence (RBC-TI) 182d were higher in the lenalidomide 10mg (57.4%; P<0.0001) and 5mg (37.2%; P=0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major+minor responses) were 56.8% (P<0.0001), 23.1% (P=0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10mg, 5mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI 182d vs. non-responders (P=0.0072). The most common grade 3-4 adverse event was myelosuppression. ConclusionsThese data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q).
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| 9. |
- Gustafsson, Anders, 1964-, et al.
(author)
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The curious case of interdisciplinary research deficiency : Cause or symptom of what truly ails us?
- 2017
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In: Journal of Business Research. - New York : Elsevier BV. - 0148-2963 .- 1873-7978. ; 79, s. 212-218
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Journal article (peer-reviewed)abstract
- This article introduces some service research challenges and opportunities then comments on the articles in this special issue on emergent topics in service research. It is an exciting time for service research as the area is rapidly developing and growing on a global basis. Service research is also especially apt for interdisciplinary as service is not developed by any one function in a company; it is a purpose in some way for everyone across the organization regardless of where they are working. It is strange, then, that we have not advanced further on interdisciplinary research, particularly since it has been in focus for a long time in the field. In this opinion piece we take the opportunity to suggest ways forward that include goals of mastering paradoxical thinking and making a difference.
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| 10. |
- Kappos, Ludwig, et al.
(author)
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Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
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Journal article (peer-reviewed)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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