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- Menkveld, Albert J., et al.
(author)
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Nonstandard Errors
- 2024
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In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Journal article (peer-reviewed)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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- Ali, M, et al.
(author)
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Protocol for the development of the international population registry for aphasia after stroke (I-PRAISE)
- 2022
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In: Aphasiology. - : Informa UK Limited. - 0268-7038 .- 1464-5041. ; 36:4, s. 534-554
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Journal article (peer-reviewed)abstract
- Background: We require high-quality information on the current burden, the types of therapy and resources available, methods of delivery, care pathways and long-term outcomes for people with aphasia.Aim: To document and inform international delivery of post-stroke aphasia treatment, to optimise recovery and reintegration of people with aphasia.Methods & Procedures: Multi-centre, prospective, non-randomised, open study, employing blinded outcome assessment, where appropriate, including people with post-stroke aphasia, able to attend for 30 minutes during the initial language assessment, at first contact with a speech and language therapist for assessment of aphasia at participating sites. There is no study-mandated intervention. Assessments will occur at baseline (first contact with a speech and language therapist for aphasia assessment), discharge from Speech and Language Therapy (SLT), 6 and 12-months post-stroke. Our primary outcome is changed from baseline in the Amsterdam Nijmegen Everyday Language Test (ANELT/Scenario Test for participants with severe verbal impairments) at 12-months post-stroke. Secondary outcomes at 6 and 12 months include the Therapy Outcome Measure (TOMS), Subjective Index of Physical and Social Outcome (SIPSO), Aphasia Severity Rating Scale (ASRS), Western Aphasia Battery Aphasia Quotient (WAB-AQ), stroke and aphasia quality of life scale (SAQoL-39), European Quality of Life Scale (EQ-5D), lesion description, General Health Questionnaire (GHQ-12), resource use, and satisfaction with therapy provision and success. We will collect demography, clinical data, and therapy content. Routine neuroimaging and medication administration records will be accessed where possible; imaging will be pseudonymised and transferred to a central reading centre. Data will be collected in a central registry. We will describe demography, stroke and aphasia profiles and therapies available. International individual participant data (IPD) meta-analyses will examine treatment responder rates based on minimal detectable change & clinically important changes from baseline for primary and secondary outcomes at 6 and 12 months. Multivariable meta-analyses will examine associations between demography, therapy, medication use and outcomes, considering service characteristics. Where feasible, costs associated with treatment will be reported. Where available, we will detail brain lesion size and site, and examine correlations with SLT and language outcome at 12 months.Conclusion: International differences in care, resource utilisation and outcomes will highlight avenues for further aphasia research, promote knowledge sharing and optimise aphasia rehabilitation delivery. IPD meta-analyses will enhance and expand understanding, identifying cost-effective and promising approaches to optimise rehabilitation to benefit people with aphasia.
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- Gallud, A, et al.
(author)
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Cationic gold nanoparticles elicit mitochondrial dysfunction: a multi-omics study
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 4366-
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Journal article (peer-reviewed)abstract
- Systems biology is increasingly being applied in nanosafety research for observing and predicting the biological perturbations inflicted by exposure to nanoparticles (NPs). In the present study, we used a combined transcriptomics and proteomics approach to assess the responses of human monocytic cells to Au-NPs of two different sizes with three different surface functional groups, i.e., alkyl ammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated Au-NPs. Cytotoxicity screening using THP-1 cells revealed a pronounced cytotoxicity for the ammonium-terminated Au-NPs, while no cell death was seen after exposure to the carboxylated or PEG-modified Au-NPs. Moreover, Au-NR3+ NPs, but not the Au-COOH NPs, were found to trigger dose-dependent lethality in vivo in the model organism, Caenorhabditis elegans. RNA sequencing combined with mass spectrometry-based proteomics predicted that the ammonium-modified Au-NPs elicited mitochondrial dysfunction. The latter results were validated by using an array of assays to monitor mitochondrial function. Au-NR3+ NPs were localized in mitochondria of THP-1 cells. Moreover, the cationic Au-NPs triggered autophagy in macrophage-like RFP-GFP-LC3 reporter cells, and cell death was aggravated upon inhibition of autophagy. Taken together, these studies have disclosed mitochondria-dependent effects of cationic Au-NPs resulting in the rapid demise of the cells.
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- Boiesen, P, et al.
(author)
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Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group
- 2000
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 39:1, s. 41-45
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Journal article (peer-reviewed)abstract
- Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.
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- Brauner, S, et al.
(author)
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Augmented Th17 differentiation in Trim21 deficiency promotes a stable phenotype of atherosclerotic plaques with high collagen content
- 2018
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In: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 114:1, s. 158-167
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Journal article (peer-reviewed)abstract
- AimsPatients with hyperlipidemia are at risk of atherosclerosis, but not all develop cardiovascular disease, highlighting the importance of other risk factors such as inflammation. Both the innate and adaptive arms of the immune system have been suggested in the initiation and propagation of plaque formation. Tri-partite motif (TRIM) 21 is a regulator of tissue inflammation and pro-inflammatory cytokine production, and has been implicated in chronic inflammatory disease. Here, we investigate a potential role for TRIM21 in coronary artery disease.Methods and resultsTrim21-deficient or wild-type bone marrow was transplanted into Ldlr-/- mice fed a hypercholesterolemic diet. The Trim21-/-->Ldlr-/- mice developed larger atherosclerotic plaques, with significantly higher collagen content compared to mice transplanted with wild-type cells. High collagen content of the atheroma is stabilizing, and has recently been linked to IL-17. Interestingly, Trim21-/-->Ldlr-/- mice had elevated CD4 and IL-17 mRNA expression in plaques, and increased numbers of activated CD4+ T cells in the periphery. An increased differentiation of naïve T cells lacking Trim21 into Th17 cells was confirmed in vitro, with transcriptomic analysis revealing upregulation of genes of a non-pathogenic Th17 phenotype. Also, decreased expression of matrix metalloproteinases (MMPs) was noted in aortic plaques. Analysis of human carotid plaques confirmed that TRIM21 expression negatively correlates with the expression of key Th17 genes and collagen, but positively to MMPs also in patients, linking our findings to a clinical setting.ConclusionIn this study, we demonstrate that TRIM21 influences atherosclerosis via regulation of Th17 responses, with TRIM21 deficiency promoting IL-17 expression and a more fibrous, stable, phenotype of the plaques.
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- Frieler, K, et al.
(author)
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Assessing the impacts of 1.5° C global warming - simulation protocol of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2b)
- 2017
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In: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10, s. 4321-4345
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Journal article (peer-reviewed)abstract
- In Paris, France, December 2015, the Conference of the Parties (COP) to the United Nations Framework Con- vention on Climate Change (UNFCCC) invited the Inter- governmental Panel on Climate Change (IPCC) to provide a “special report in 2018 on the impacts of global warming of 1.5 â—ŠC above pre-industrial levels and related global green- house gas emission pathwaysâ€. In Nairobi, Kenya, April 2016, the IPCC panel accepted the invitation. Here we de- scribe the response devised within the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) to provide tailored, cross-sectorally consistent impact projections to broaden the scientific basis for the report. The simulation protocol is de- signed to allow for (1) separation of the impacts of histori- cal warming starting from pre-industrial conditions from im- pacts of other drivers such as historical land-use changes (based on pre-industrial and historical impact model simula- tions); (2) quantification of the impacts of additional warm- ing up to 1.5 â—ŠC, including a potential overshoot and long- term impacts up to 2299, and comparison to higher lev- els of global mean temperature change (based on the low- emissions Representative Concentration Pathway RCP2.6 and a no-mitigation pathway RCP6.0) with socio-economic conditions fixed at 2005 levels; and (3) assessment of the cli- mate effects based on the same climate scenarios while ac- counting for simultaneous changes in socio-economic con- ditions following the middle-of-the-road Shared Socioeco- nomic Pathway (SSP2, Fricko et al., 2016) and in particu- lar differential bioenergy requirements associated with the transformation of the energy system to comply with RCP2.6 compared to RCP6.0.With the aim of providing the scientific basis for an aggregation of impacts across sectors and anal- ysis of cross-sectoral interactions that may dampen or am- plify sectoral impacts, the protocol is designed to facilitate consistent impact projections from a range of impact mod- els across different sectors (global and regional hydrology, lakes, global crops, global vegetation, regional forests, global and regional marine ecosystems and fisheries, global and regional coastal infrastructure, energy supply and demand, temperature-related mortality, and global terrestrial biodiver- sity).
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- Ringberg, Anita, et al.
(author)
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Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast
- 2000
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 1532-2157 .- 0748-7983. ; 26:5, s. 444-451
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Journal article (peer-reviewed)abstract
- METHOD AND RESULTS: A standardized histopathological protocol has been designed, in which different histological characteristics of ductal carcinoma in situ (DCIS) are reported: nuclear grade (ng), growth pattern according to Andersen et al., necrosis, size of the lesion, resection margins and focality. Using this protocol a re-evaluation of a population-based consecutive series of 306 cases of DCIS has been done as well as a thorough clinical follow-up. After a median follow-up of 63 months, 13% have developed ipsilateral local recurrences, invasive and/or in situ. Ipsilateral local recurrence-free survival (IL-RFS) was significantly better for patients operated with mastectomy (ME) or breast conserving therapy (BCT) with radiotherapy (RT) than for patients operated with BCT without RT (5-year IL-RFS 96% vs 94% vs 79%, P<0.001). In the subgroup of BCT without RT there were significant differences in IL-RFS between histopathological subgroups: ng 1 + 2 (non-high grade) vs ng 3 (high grade; P=0.014), non-high-grade without comedo-type necrosis vs non-high-grade with comedo-type necrosis vs high-grade (the Van Nuys classification system; P=0.025). Growth pattern (not diffuse vs diffuse) and margins (free vs involved or not evaluated) showed a tendency (P=0.07 and 0.05, respectively) to be associated to IL-RFS. In contrast, no significant differences in IL-RFS were found in subgroups based on mode of detection, focality or size. Ninety-four per cent of the local recurrences after BCT appeared at the previous operation site. CONCLUSIONS: In the BCT without RT group, combinations of either non-high grade and not a diffuse growth pattern or non-high grade and free margins identified groups (constituting approximately 30% of the patients) were at low risk of developing ipsilateral recurrences (6-10%), compared to a 31-37% recurrence risk in the remaining groups during the observed follow-up time. The beneficial effect of post-operative RT for these low-risk groups can be questioned, and should be studied further.
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| 25. |
- Strombergsson, S, et al.
(author)
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Towards an Integrated Curriculum in a Speech and Language Pathology Education Programme: Development and Constituents' Initial Responses
- 2020
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In: Folia phoniatrica et logopaedica : official organ of the International Association of Logopedics and Phoniatrics (IALP). - : S. Karger AG. - 1421-9972. ; 72:1, s. 52-63
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> A traditional curricular structure may challenge integration between foundational and clinical sciences in speech and language pathology (SLP) education. This project aimed to increase curriculum integration at a Swedish SLP education programme. <b><i>Methods:</i></b> Learning outcomes in the existent curriculum were copied from their original courses and re-structured with reference to vertical tracks, in order to address them within and across years of study. A content analysis of interviews with teachers and students was conducted for the evaluation of curricular change. <b><i>Results:</i></b> Among the changes were earlier introduction to clinical science and revisiting of foundational sciences later in the education. Theme concepts were defined to scaffold horizontal integration, whereas revisited use of documented material was formalized to ensure vertical integration. In evaluation interviews, multiple examples were provided of how the new curriculum was perceived as being more integrated, with horizontal themes and vertical tracks providing structure. Concerns raised highlight the importance of appointing clear responsibilities. <b><i>Conclusions:</i></b> The concepts “gaps” and “overlaps” may guide remediation of areas where increased curricular integration is warranted. Serial child observations running through the curriculum may provide a platform for both horizontal and vertical integration. For maintenance of curricular integration, clear responsibilities are needed, stretching across course and semester boundaries.
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