| 1. |
|
|
| 2. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 4. |
- Breznau, Nate, et al.
(författare)
-
Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
|
|
| 5. |
- Sønderby, Ida E., et al.
(författare)
-
1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
-
Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
|
|
| 6. |
- van der Meer, Dennis, et al.
(författare)
-
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
-
Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
|
|
| 7. |
- Boen, Rune, et al.
(författare)
-
Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
-
Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
|
|
| 8. |
|
|
| 9. |
- da Bandeira, Diana Sa, et al.
(författare)
-
PDGFR beta(+) cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny
- 2022
-
Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 40:3
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell (HSC) generation in the aorta-gonad-mesonephros region requires HSC specification signals from the surrounding microenvironment. In zebrafish, PDGF-B/PDGFR beta signaling controls hematopoietic stem/progenitor cell (HSPC) generation and is required in the HSC specification niche. Little is known about murine HSPC specification in vivo and whether PDGF-B/PDGFR beta is involved. Here, we show that PDGFR beta is expressed in distinct perivascular stromal cell layers surrounding the mid-gestation dorsal aorta, and its deletion impairs hematopoiesis. We demonstrate that PDGFR beta(+) cells play a dual role in murine hematopoiesis. They act in the aortic niche to support HSPCs, and in addition, PDGFR beta(+) embryonic precursors give rise to a subset of HSPCs that persist into adulthood. These findings provide crucial information for the controlled production of HSPCs in vitro.
|
|
| 10. |
- Jones, Benedict C, et al.
(författare)
-
To which world regions does the valence-dominance model of social perception apply?
- 2021
-
Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
-
Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
|
|
| 11. |
- ODonnell, Michael, et al.
(författare)
-
Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
-
Ingår i: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
-
Tidskriftsartikel (refereegranskat)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
|
|
| 12. |
- Wiemhoefer, Anne, et al.
(författare)
-
Tripeptidyl Peptidase II Mediates Levels of Nuclear Phosphorylated ERK1 and ERK2
- 2015
-
Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 14:8, s. 2177-2193
-
Tidskriftsartikel (refereegranskat)abstract
- Tripeptidyl peptidase II (TPP2) is a serine peptidase involved in various biological processes, including antigen processing, cell growth, DNA repair, and neuropeptide mediated signaling. The underlying mechanisms of how a peptidase can influence this multitude of processes still remain unknown. We identified rapid proteomic changes in neuroblastoma cells following selective TPP2 inhibition using the known reversible inhibitor butabindide, as well as a new, more potent, and irreversible peptide phosphonate inhibitor. Our data show that TPP2 inhibition indirectly but rapidly decreases the levels of active, di-phosphorylated extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the nucleus, thereby down-regulating signal transduction downstream of growth factors and mitogenic stimuli. We conclude that TPP2 mediates many important cellular functions by controlling ERK1 and ERK2 phosphorylation. For instance, we show that TPP2 inhibition of neurons in the hippocampus leads to an excessive strengthening of synapses, indicating that TPP2 activity is crucial for normal brain function.
|
|
| 13. |
- Ahlgren, Ewa, 1959-
(författare)
-
Cerebral complications after cardiac surgery
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral injuty remains a major cause of morbidity and mortality after cardiac surgery. Previous studies have mainly focused on preoperative risk factors and intraoperative events but cerebral complications may also occur in the postoperative period. Cognitive impairment is common after cardiac surgery but the consequences of this complication for activities of daily life are less known. Safe driving involves a complex set of skills requiring preserved cognitive function. A substantial number of patients with heart disease are active drivers. The impact of postoperative cognitive dysfunction on driving performance, however, has not previously been investigated in this large patient group.In this thesis pre-, intra- and postoperative risk factors for focal cerebral complications were determined and the onset time of cerebral symptoms were evaluated in two cohorts of cardiac surgical patients, comprising 2480 and 3282 patients respectively. Data analysed were drafted from a clinical register and the surgical database of Linköping University Hospital Heart Center. Cerebral complication was delayed, i.e occurred after a free interval, in about one third of patients suggesting causes other than intraoperative events. Different risk factors were found for early and delayed cerebral complications suggesting different mechanisms of cerebral injury. Advanced age, preoperative hypertension, aortic surgery, prolonged cardiopulmonary bypass (CPB) time, intraoperative hypotension after completion of CPB, and arrhytlunia in the early postoperative period increased the risk for early cerebral complication. Female gender, diabetes, previous cerebrovascular disease, combined coronary artery bypass grafting (CABG) and valve surgery and arrhythmia on the thoracic ward increased the risk for delayed cerebral complication. Cognitive function and driving performance were evaluated in 27 patients before and 4-6 weeks after CABG. The patients underwent neuropsychological testing, an on-road driving test and a test in an advanced driving simulator. Twenty patients scheduled for percutaneous coronary intervention (PCI) served as controls. Complete data were obtained in 23 and 19 patients respectively. Furthermore cognitive function and driving performance in on-road driving of the 44 patients with complete tests before intervention were compared with controls of similar age without heart symptoms. Cognitive function and driving performance were already impaired in patients with coronary artery disease before intervention when compared with controls. After surgery 48% of the patients showed cognjtive decline compared to 10% after PCI. These patients also scored less in the on-road driving test to a greater extent than did patients without postoperative cognitive decline.
|
|
| 14. |
- Borowiec, Jan, et al.
(författare)
-
Heparin-coated cardiopulmonary bypass circuits and 25% reduction of heparin dose in coronary artery surgery : a clinical study
- 1992
-
Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 97:1, s. 55-66
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary bypass with systemic heparinization causes trauma to blood cells and coagulation defects. Artificial surfaces could be coated by end-linkage binding of heparin (Carmeda Bioactive Surface, CBAS). Use of such surfaces during cardiopulmonary bypass in animals resulted in less postoperative blood loss and better preservation of blood cells. In this study heparin-coated circuits were employed during coronary artery grafting in 7 patients (Group HC). Concomitantly, the heparin dose was reduced by 25% and an activated clotting time (ACT) of 300 sec was accepted. Additional 7 patients were operated with standard circuits (Group C), requiring ACT above 400 sec with normal doses of heparin. There were no thromboembolic complications in Group HC. The postoperative bleeding was generally low and without significant intergroup differences. Coagulation parameters displayed significantly lower ACT and anti-Factor Xa during bypass in Group HC. A tendency towards less blood cell trauma was observed with heparin-coated circuits. The protamine dose could be reduced by 50%, which significantly reduced the protamine/heparin quotient. This study indicates that routine cardiopulmonary bypass could be performed safely with heparin-coated circuits and reduced intravenous doses of heparin and protamine. It is suggested that the use of heparin-coated circuits may lead to less blood cell trauma.
|
|
| 15. |
- Cosyn, Jan, et al.
(författare)
-
Minimally Invasive Single Implant Treatment (MISIT) based on ridge preservation and contour augmentation in patients with a high aesthetic risk profile : one-year results
- 2015
-
Ingår i: Journal of Clinical Periodontology. - : John Wiley & Sons. - 0303-6979 .- 1600-051X. ; 42:4, s. 398-405
-
Tidskriftsartikel (refereegranskat)abstract
- AimTo evaluate the 1-year outcome of Minimally Invasive Single Implant Treatment (M.I.S.I.T.) based on ridge preservation and contour augmentation in patients with a high aesthetic risk profile. Materials and MethodsPeriodontally healthy non-smoking patients with a failing tooth in the anterior maxilla (15-25) were selected. All were in need of a single implant and demonstrated high risk for aesthetic complications given mid-facial recession at the failing tooth and/or a buccal bone dehiscence and/or a thin-scalloped gingival biotype. Patients without mid-facial recession (NRG) received flapless tooth extraction and ridge preservation using a collagen-enriched bovine-derived xenograft, flapless installation of a bone condensing implant with variable-thread design (4-6months later), a provisional screw-retained crown and connective tissue graft (CTG) inserted in the buccal mucosa (3months later) and a permanent crown (3months later). Patients with mid-facial recession (RG) were treated similarly, yet they received a CTG at the time of ridge preservation. All patients were treated by an experienced periodontist using a microsurgical approach. Primary outcome variables included papillary and mid-facial recession. Clinical parameters, pink (PES) and white aesthetic score (WES) were considered secondary outcome variables. ResultsFifty patients (25 females, 25 males; mean age 39, range 19-81; 42 in NRG and 8 in RG) met the selection criteria and consented to the treatment. Forty-seven could be examined at 12months and all implants survived. Mean bone loss amounted to 0.48mm (range 0.00-1.80) at 12months. Papillary recession was minimal in both groups at 12months (mean0.3mm), as was mid-facial recession in the NRG (mean 0.1mm). Twelve patients in the NRG even demonstrated coronal migration of the mucosal margin following CTG and needed adaptation of the provisional crown to induce soft tissue retraction. Due to CTG at the time of ridge preservation in the RG, mid-facial soft tissue gain amounted to 0.9mm at 12months, hereby eliminating 2/3rd of the initial recession. PES and WES were favourable pointing to 10.9/14 and 8.2/10 respectively. ConclusionThis short-term prospective study offers a proof of principle of M.I.S.I.T. in patients with a high aesthetic risk profile.
|
|
| 16. |
- Dutton, Edward, et al.
(författare)
-
The intelligence and personality of Finland's Swedish-speaking minority
- 2016
-
Ingår i: Personality and Individual Differences. - : Elsevier BV. - 0191-8869 .- 1873-3549. ; 97, s. 45-49
-
Tidskriftsartikel (refereegranskat)abstract
- There is evidence that Finland's Swedish-speaking minority (Finland-Swedes) may have a distinct intelligence-personality profile from the Finnish-speaking Finns (Finns). We test this through an examination of the two groups' PISA (Programme of International Student Assessment) scores (which assesses representative samples of 15 year olds from OECD countries) and their personality scores, drawing upon a representative Finnish sample. We found Finland-Swedes to have slightly lower average intelligence. However, when controlling for gender and age, the Finland-Swedes score significantly higher on Conscientiousness, Extraversion and Emotional Stability. Overall, we found a Jensen Effect whereby most of the personality differences between the two groups could be attributed to the General Factor of Personality (GFP), which reflects the shared variance of lower-order personality traits. The GFP is assumed to reflect general social effectiveness.
|
|
| 17. |
- Dutton, Edward, 1980-, et al.
(författare)
-
The myth of the stupid believer : The negative religiousness-IQ nexus is not on general intelligence (g) and is likely a product of the relations between IQ and Autism Spectrum traits
- 2020
-
Ingår i: Journal of religion and health. - : Springer. - 0022-4197 .- 1573-6571. ; 59:3, s. 1567-1579
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have found a negative relationship between religiousness and IQ. It is in the region of - 0.2, according to meta-analyses. The reasons for this relationship are, however, unknown. It has been suggested that higher intelligence leads to greater attraction to science, or that it helps to override evolved cognitive dispositions such as for religiousness. Either way, such explanations assume that the religion-IQ nexus is on general intelligence (g), rather than some subset of specialized cognitive abilities. In other words, they assume it is a Jensen effect. Two large datasets comparing groups with different levels of religiousness show that their IQ differences are not on g and must, therefore, be attributed to specialized abilities. An analysis of the specialized abilities on which the religious and non-religious groups differ reveals no clear pattern. We cautiously suggest that this may be explicable in terms of autism spectrum disorder traits among people with high IQ scores, because such traits are negatively associated with religiousness.
|
|
| 18. |
- Elfwen, Ludvig, et al.
(författare)
-
Direct or subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)-An initial pilot-study of a randomized clinical trial
- 2019
-
Ingår i: Resuscitation. - : ELSEVIER IRELAND LTD. - 0300-9572 .- 1873-1570. ; 139, s. 253-261
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the 'DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest' (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods: Resuscitated bystander witnessed OHCA patients > 18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results: In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion: In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.
|
|
| 19. |
|
|
| 20. |
- Hartmann, H., et al.
(författare)
-
Risk based testing for software product line engineering
- 2014
-
Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : ACM. ; 1, s. 227-231
-
Konferensbidrag (refereegranskat)abstract
- The variability of product lines increases over time thereby leading to an increasing effort for testing. Since the available time for test activities is limited an efficiency improvement is needed to ensure that products have sufficient quality. This paper introduces risk-based testing for software product lines. Our approach is based on risk based testing for single system engineering which is extended with a dimension that captures the percentage of product variants that use a particular development artifact. Based on the risk of development artifacts, the priorities for domain and application engineering are determined. We demonstrate our approach using a case study from an existing product line and discuss tool support. We conclude that the basic ideas behind risk-based testing for product lines are intuitive, pragmatic in nature, and provide the means for practitioners for guiding the test effort. Copyright 2014 ACM.
|
|
| 21. |
- Hedberg, Magnus, 1981-
(författare)
-
Stroke during cardiac surgery : risk factors, mechanisms and survival effects
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Neurological complications and stroke in association with cardiac surgery is a serious problem. The stroke event can occur during surgery (early stroke) or in the postoperative period with a symptom free interval (delayed stroke). Particle embolization due to aortic manipulation during surgery has been suspected as a mechanism for early stroke. The present thesis address mechanisms and survival effects of stroke both clinically (I-III) and experimentally (IV-V). Methods: Study I) Within a cohort of 2641 consecutive cases, a group of cardiac surgery patients with stroke and evaluated by computed tomography (CT) were studied (n=77). CT-findings were analyzed in relation to stroke symptoms. Study II) Data from 9122 patients undergoing coronary surgery were analyzed. Records of patients with any signs of neurological complications were reviewed to extract 149 subjects with stroke at extubation (early, 1.6%) versus 99 patients having a free interval (delayed, 1.1%). Early and delayed stroke were evaluated separately. Independent risk factors for stroke were analyzed by logistic regression and survival by Cox regression (9.3 years median follow-up). Study III) Patients with early (n=223) and delayed stroke (n=116) were identified among 10809 patients undergoing cardiac and aortic surgery, both groups exposed to cardiopulmonary bypass. Stroke patients were subdivided by the hemispheric location of lesions. Subgroups were compared and their associated pre- and peroperative variables and survival were analyzed. Study IV) Aortic cross-clamp manipulation was studied in a human cadaveric perfusion model. The pressurized aorta was repeatedly cross-clamped and washout samples were collected before and after clamp maneuvers. Particles in the washout samples were evaluated by microscopy and by digital image analysis. Study V) Pig aortas were pressurized and cannulated. Washout samples were collected before and after cannulation (n = 40). Particles were deposited onto a 10-μm filter to be evaluated by microscopy and digital image analysis. Results: Study I) In the group of patients exposed to routine cardiac surgery (i.e., clamping and cannulation) and with early stroke, right-hemispheric lesions were more frequent than of the contra-lateral side (P=0.005). Patients with aortic dissections had a strong dominance of bilateral findings, which was different from the unilateral pattern in the routine-surgery group (P<0.001). Study II) Early and delayed stroke did not share any risk factors. Both early and delayed stroke explained mortality in the early postoperative period (P<0.001, P<0.001 respectively) but also at long term follow-up (P=0.008, P<0.001 respectively). For patients surviving their first postoperative year, delayed but not early stroke influenced long-term mortality (P=0.001 and P=0.695, respectively). Study III) Stroke lesions in association to cardiac surgery were near exclusively ischemic. Early stroke had a preponderance for right-hemispheric lesions (P=0.009). In contrast, patients with early stroke that had undergone surgery of the aorta with circulatory arrest showed a pattern with more bilateral lesions compared to ‘cardiac-type’ operations (P<0.001). Patients with bilateral lesions had a dramatically impaired survival compared to those with unilateral lesions (P<0.001). Study IV) In the cadaveric perfusion model, cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (P=0.002 to P=0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification (P =0.002 to P=0.025). Study V) At cannulation of the pig aorta, more particles were noted after cannulation compared to before the maneuver (P<0.001). This increase included small (<0.1 mm, P<0.001) and intermediate-size particles (0.1-0.5 mm, P< 0.001). Particles above 0.5 mm were few and were not associated with cannulation. Conclusions: The influence of stroke on mortality was devastating, for both early and delayed stroke. These two stroke groups had obvious differences in both their risk factors and their hemispheric distribution. It is here emphasized that early and delayed stroke should be considered as two separate entities with suggested mechanistic differences. Ischemic lesions accounted for near all stroke events seen in association to cardiac surgery. For early stroke, these were mostly located within the right hemisphere. Results from the experimental studies underscore microembolic risks associated with aortic manipulation.
|
|
| 22. |
- Holm, Jonas, 1971-
(författare)
-
Markers of hemodynamic state and heart failure as predictors for outcome in cardiac surgery : with special reference to mixed venous oxygen saturation and natriuretic peptides
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Postoperative heart failure or low cardiac output syndrome is the major cause for morbidity and mortality in cardiac surgery. Unfortunately commonly used methods to assess hemodynamic state and heart failure are not well documented with regard to outcome. The aim for this dissertation was to study the predictive values of postoperative Mixed Venous Oxygen saturation (SvO2) and preoperative NT-proBNP for outcomes related to postoperative heart failure.SvO2 was studied retrospectively in two cohorts of patients, one cohort operated with isolated Aortic Valve Replacement (AVR) for aortic stenosis, (n=396) and one operated with isolated Coronary Artery Bypass Grafting (CABG), (n=2755). SvO2 measured early after surgery, on admission to the intensive care unit (ICU), predicted postoperative morbidity and mortality. Our results suggest that, on admission to ICU SvO2 < 55 - 60% after AVR and SvO2 < 60% after CABG merits increased attention.Preoperative NT-proBNP was studied in a cohort of patients with acute coronary syndrome (ACS) undergoing CABG with or without concomitant procedure. These patients (n=383) were included prospectively and evaluated with regard to mortality and severe circulatory failure postoperatively by an end-points committee blinded to NT-proBNP results. Preoperative NT-proBNP ≥ 1028 ng/L independently predicted increased risk for severe circulatory failure postoperatively in patients with ACS undergoing isolated CABG. Preoperative NT-proBNP provided additional prognostic information to EuroSCORE II in this cohort, particularly in patients at intermediate risk. Preoperative NT-proBNP appears to be markedly higher in patients having CABG with concomitant procedures than in patients undergoing isolated CABG. Further studies are warranted to identify preoperative NTproBNP risk thresholds for different heart conditions and surgery-specific cohorts.In conclusion this dissertation shows that:Postoperative SvO2 on admission to ICU is a prognostic marker for morbidity and mortality after AVR and CABG.Preoperative NT-proBNP ≥ 1028 ng/L independently predicts severe circulatory failure postoperatively in patients undergoing isolated CABG and provides additional prognostic information to EuroSCORE II.The high negative predictive value of the identified cutoff levels for preoperative NTproBNP and postoperative SvO2 could be useful for pre and postoperative decisionmaking.
|
|
| 23. |
- Jurga, Juliane, et al.
(författare)
-
Does Coronary Angiography and Percutaneous Coronary Intervention Affect Cognitive Function?
- 2016
-
Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 118:10, s. 1437-1441
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebral microemboli are frequently observed during coronary angiography (CA) and percutaneous coronary intervention (PCI), and their numbers have been related to the vascular access site used. Although cerebral microemboli can cause silent cerebral lesions, their clinical impact is debated. To study this, 93 patients referred for CA or PCI underwent serial cognitive testing using the Montreal Cognitive Assessment (MoCA) test to detect postprocedural cognitive impairment. Patients were randomized to radial or femoral access. In a subgroup of 35 patients, the number of cerebral microemboli was monitored with transcranial Doppler technique. We found the median precatheterization result of the MoCA test to be 27, and it did not change significantly 4 and 31 days, respectively, after the procedure. There was no significant correlation between the number of cerebral microemboli and the difference between preprocedural and postprocedural MoCA tests. The test results did not differ between vascular access sites. One-third of the patients had a precatheterization median MoCA test result <26 corresponding to mild cognitive impairment. In conclusion, using the MoCA test, we could not detect any cognitive impairment after CA or PCI, and no significant correlations were found between the results of the MoCA test and cerebral microemboli or vascular access site, respectively. In patients with suspected coronary heart disease, mild cognitive impairment was common.
|
|
| 24. |
- Kjellberg, Gunilla, et al.
(författare)
-
Calculation Algorithm Reduces Protamine Doses Without Increasing Blood Loss or the Transfusion Rate in Cardiac Surgery : Results of a Randomized Controlled Trial
- 2019
-
Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:4, s. 985-992
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of the study was to investigate whether the HeProCalc algorithm affects heparin and protamine dosage, postoperative blood loss, and transfusion rate.Design: Randomized controlled trial.Setting: University hospital.Participants: The study comprised 210 cardiac surgery patients undergoing cardiac surgery with cardiopulmonary bypass. Twenty patients were excluded because of re-exploration for localized surgical bleeding (n = 9), violation of protocol (n = 2), aprotinin use (n = 3 and nadir body temperature <32 degrees C (n = 6).Interventions: Study participants were randomly assigned to either traditional heparin and protamine dosage based on body weight only (control group) or dosage based on the HeProCalc algorithm (intervention group).Measurements and Main Results: The initial median heparin dose was 32,500 IU (interquartile range [IQR] 30,000-35,000) in the intervention group compared with 35,000 IU (IQR 30,000-37,500) (p = 0.025) in the control group. The total heparin dose in the intervention group was 40,000 IU (1QR 32,500-47,500) compared with 42,500 IU (IQR 35,000-50,000) in the control group (p = 0.685). The total protamine dose was 210 mg (IQR 190-240) in the intervention group compared with 350 mg (IQR 300-380) (p < 0.001) in the control group. The ratio of total protamine to initial dose of heparin in the intervention group was 0.62 compared with 1.0 (p < 0.001). The amount of chest tube bleeding after 12 postoperative hours was 320 mL (IQR 250-460) in the intervention group compared with 350 mL (IQR 250-450) (p = 0.754) in the control group. Neither the transfusion rate nor postoperative blood loss differed significantly between the 2 groups.Conclusion: Use of the HeProCalc algorithm reduced protamine dosage and the protamine/heparin ratio after cardiopulmonary bypass compared with conventional dosage based on weight without significant effect on postoperative blood loss or the transfusion rate.
|
|
| 25. |
|
|
| 26. |
- Olsson, Christian, 1973-
(författare)
-
Thoracic Aortic Surgery : Epidemiology, Outcomes, and Prevention of Cerebral Complications
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mortality of thoracic aortic diseases (mainly aneurysms and dissections) is high, even with surgical treatment. Epidemiology and long-term outcomes are incompletely investigated. Stroke is a major complication contributing to mortality, morbidity, and possibly to reduced quality of life. Study I Increasing incidence of thoracic aortic diseases 1987 – 2002 was demonstrated (n=14229). Annual number of operations increased eight-fold. Overall long-time survival was 92%, 77%, and 57% at 1, 5, and 10 years. Risk of operative and long-term mortality was reduced across time. Study II 2634 patients operated on the proximal thoracic aorta (Swedish Heart Surgery register) were examined. Aortic valve replacement, coronary revascularization, emergency operation, and age were independently associated with surgical death. Long-term mortality was similar for aneurysms and dissections. Operative mortality was reduced (13.7% vs 7.2%) for aneurysms but remained unchanged (22.3% vs 22.4%) for dissections across time. Study III 65 patients underwent selective antegrade cerebral perfusion (SACP) uni- or bilaterally. Stroke was significantly more common after unilateral SACP (29% vs 8%, p=0.045), confirmed by propensity score-matched analysis. Subclavian artery cannulation with Seldinger-technique entailed vascular complication in one case (1.5%). Study IV Near-infrared spectroscopy (NIRS) was used to monitor cerebral tissue saturation (rSO2) during SACP in 46 patients. Lower rSO2 were encountered (1) in patients suffering a stroke (2) with unilateral SACP, and (3) in the affected hemisphere of stroke victims. A decrease of rSO2 by 14 – 21% from baseline increased the risk of stroke significantly. Study V Quality of life (QoL) in 76 survivors of thoracic aortic surgery was examined with the SF-36 health questionnaire. Except for pain, QoL was reduced in all dimensions. QoL was not affected by acuity of operation. Tendencies of lower QoL after descending aortic operations, after major complications, and with persistent dysfunction were non-significant.
|
|
| 27. |
- Ortgies, Robert, et al.
(författare)
-
CHORUS Deliverable 3.3: Vision Document - Intermediate version
- 2008. - 1
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The goal of the CHORUS vision document is to create a high level vision on audio-visual search engines in order to give guidance to the future R&D work in this area (in line with the mandate of CHORUS as a Coordination Action). This current intermediate draft of the CHORUS vision document (D3.3) is based on the previous CHORUS vision documents D3.1 to D3.2 and on the results of the six CHORUS Think-Tank meetings held in March, September and November 2007 as well as in April, July and October 2008, and on the feedback from other CHORUS events. The outcome of the six Think-Thank meetings will not just be to the benefit of the participants which are stakeholders and experts from academia and industry – CHORUS, as a coordination action of the EC, will feed back the findings (see Summary) to the projects under its purview and, via its website, to the whole community working in the domain of AV content search. A few subjections of this deliverable are to be completed after the eights (and presumably last) Think-Tank meeting in spring 2009.
|
|
| 28. |
- van der Linden, Helma, et al.
(författare)
-
Generic Screen Representations for Future Proof Systems - Is It Possible? : Two-Model Approach to a Generic GUI
- 2007
-
Ingår i: MEDINFO 2007: Proceedings of the 12th World Congress on Health (Medical) Informatics, Pts 1 and 2. - : IOS Press. - 9781586037741 ; , s. 1122-1126
-
Konferensbidrag (refereegranskat)abstract
- Semantic interoperability should not only cover system interpretation of incoming information, but should be extended to include screen representation. This article describes a two-model approach to generate a screen representation for archetype-based information, which is inspired by the two-model approach used by openEHR for their archetypes. It provides a separation between software-related display knowledge and domain-related display knowledge and is designed with reuse of components in mind. This approach leads to a flexible GUI that can adapt not only to information structures that are not predefined within the receiving system and display them in a meaningful way, but also to novel ways of displaying the information.We are working on a proof of concept implementation to validate the approach.
|
|
| 29. |
|
|
