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| 3. |
- Mollenhauer, B., et al.
(författare)
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Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:11, s. 1999-2008
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Tidskriftsartikel (refereegranskat)abstract
- Background The objective of this study was to assess neurofilament light chain as a Parkinson's disease biomarker. Methods We quantified neurofilament light chain in 2 independent cohorts: (1) longitudinal cerebrospinal fluid samples from the longitudinal de novo Parkinson's disease cohort and (2) a large longitudinal cohort with serum samples from Parkinson's disease, other cognate/neurodegenerative disorders, healthy controls, prodromal conditions, and mutation carriers. Results In the Parkinson's Progression Marker Initiative cohort, mean baseline serum neurofilament light chain was higher in Parkinson's disease patients (13 +/- 7.2 pg/mL) than in controls (12 +/- 6.7 pg/mL),P= 0.0336. Serum neurofilament light chain increased longitudinally in Parkinson's disease patients versus controls (P< 0.01). Motor scores were positively associated with neurofilament light chain, whereas some cognitive scores showed a negative association. Conclusions Neurofilament light chain in serum samples is increased in Parkinson's disease patients versus healthy controls, increases over time and with age, and correlates with clinical measures of Parkinson's disease severity. Although the specificity of neurofilament light chain for Parkinson's disease is low, it is the first blood-based biomarker candidate that could support disease stratification of Parkinson's disease versus other cognate/neurodegenerative disorders, track clinical progression, and possibly assess responsiveness to neuroprotective treatments. However, use of neurofilament light chain as a biomarker of response to neuroprotective interventions remains to be assessed. (c) 2020 The Authors.Movement Disorderspublished by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.
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| 4. |
- Ruhle, S A, S A, et al.
(författare)
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“To work, or not to work, that is the question” : Recent trends and avenues for research on presenteeism
- 2020
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Ingår i: European Journal of Work and Organizational Psychology. - 1359-432X .- 1464-0643. ; 29:3, s. 344-363
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Tidskriftsartikel (refereegranskat)abstract
- This position paper brings together recent and emerging developments in the field of presenteeism. A critical synthesis of the evidence is needed due to persisting conceptual and methodological challenges as well as the increased volume of research in the field.This paper integrate semerging evidence and critical thinking into three areas: (1) concept, (2) measurement and methodological issues, and (3) the context of presenteeism. First, due to the variety of existing definitions, competing understandings, as well as the notion of positive presenteeism, it is important to reconsider the notion of presenteeism. Second, it is important to reflect on the measurement of the act of presenteeism and the productivity loss associated with that. Third,following the call to investigate presenteeism in specific contexts,it is important to explain the social, occupational, cross-cultural aspects, as well as the contemporary workplace changes. Based on this critical synthesis, we conclude by identifying recommendations for future research on presenteeism.
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| 5. |
- Eifert, S, et al.
(författare)
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Applying the Gender Lens to Risk Factors and Outcome after Adult Cardiac Surgery
- 2014
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Ingår i: Viszeralmedizin. - : S. Karger AG. - 1662-6664. ; 30:2, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background: </i></b>Applying the gender lens to risk factors and outcome after adult cardiac surgery is of major clinical interest, as the inclusion of sex and gender in research design and analysis may guarantee more comprehensive cardiovascular science and may consecutively result in a more effective surgical treatment as well as cost savings in cardiac surgery. <b><i>Methods: </i></b>We have reviewed classical cardiovascular risk factors (diabetes, arterial hypertension, hyperlipidemia, smoking) according to a gender-based approach. Furthermore, we have examined comorbidities such as depression, renal insufficiency, and hormonal influences in regard to gender. Gender-sensitive economic aspects have been evaluated, surgical outcome has been analyzed, and cardiovascular research has been considered from a gender perspective. <b><i>Results: </i></b>The influence of typical risk factors and outcome after cardiac surgery has been evaluated from a gender perspective, and the gender-specific distribution of these risk factors is reported on. The named comorbidities are listed. Economic aspects demonstrated a gender gap. Outcome after coronary and valvular surgeries as well as after heart transplantation are displayed in this regard. Results after postoperative use of intra-aortic balloon pump are shown. Gender-related aspects of clinical and biomedical cardiosurgical research are reported. <b><i>Conclusions: </i></b>Female gender has become an independent risk factor of survival after the majority of cardiosurgical procedures. Severely impaired left ventricular ejection fraction independently predicts survival in men, whereas age does in females.
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| 6. |
- Helmerson, C., et al.
(författare)
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Evidence of hybridization between genetically distinct Baltic cod stocks during peak population abundance(s)
- 2023
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Ingår i: Evolutionary Applications. - 1752-4571. ; 16:7, s. 1359-1376
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Tidskriftsartikel (refereegranskat)abstract
- Range expansions can lead to increased contact of divergent populations, thus increasing the potential of hybridization events. Whether viable hybrids are produced will most likely depend on the level of genomic divergence and associated genomic incompatibilities between the different entities as well as environmental conditions. By taking advantage of historical Baltic cod (Gadus morhua) otolith samples combined with genotyping and whole genome sequencing, we here investigate the genetic impact of the increased spawning stock biomass of the eastern Baltic cod stock in the mid 1980s. The eastern Baltic cod is genetically highly differentiated from the adjacent western Baltic cod and locally adapted to the brackish environmental conditions in the deeper Eastern basins of the Baltic Sea unsuitable for its marine counterparts. Our genotyping results show an increased proportion of eastern Baltic cod in western Baltic areas (Mecklenburg Bay and Arkona Basin)-indicative of a range expansion westwards-during the peak population abundance in the 1980s. Additionally, we detect high frequencies of potential hybrids (including F1, F2 and backcrosses), verified by whole genome sequencing data for a subset of individuals. Analysis of mitochondrial genomes further indicates directional gene flow from eastern Baltic cod males to western Baltic cod females. Our findings unravel that increased overlap in distribution can promote hybridization between highly divergent populations and that the hybrids can be viable and survive under specific and favourable environmental conditions. However, the observed hybridization had seemingly no long-lasting impact on the continuous separation and genetic differentiation between the unique Baltic cod stocks.
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| 7. |
- Jost, Stefanie T., et al.
(författare)
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Levodopa Dose Equivalency in Parkinson's Disease : Updated Systematic Review and Proposals
- 2023
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Ingår i: Movement Disorders. - 0885-3185. ; 38:7, s. 1236-1252
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Tidskriftsartikel (refereegranskat)abstract
- Background: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as ‘levodopa equivalent dose’ (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. Objectives: To update LED conversion formulae based on a systematic review. Methods: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. Results: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. Conclusions: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD.
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| 8. |
- Brovelli, M.A., et al.
(författare)
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Citizen Science in Support of Digital Earth
- 2020
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Ingår i: Manual of Digital Earth. - Singapore : Springer Verlag.
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Bokkapitel (refereegranskat)abstract
- Citizen science can be thought of as a tremendous catalyst for making Digital Earth a participation model of our world. This chapter presents a wide overview of the concept and practice of citizen science in terms of the technologies and social impact. Definitions of citizen science and various existing approaches to citizen involvement are described, from simple contributions to projects proposed by someone else to the design and planning of science as a bottom-up process. To illustrate these concepts, the relevant example of OpenStreetMap is described in detail, and other examples are mentioned and briefly discussed. Social innovation connected with citizen science is focused on to highlight different levels of direct citizen contributions to scientific research and indirect effects on academia, and studies driven by new questions that may support responsible research and innovation (RRI), governments and public administration in making better informed decisions. Despite its growth and success in relatively few years, citizen science has not fully overcome a number of persistent challenges related to quality, equity, inclusion, and governance. These themes and related complex facets are discussed in detail in the last section of the chapter.
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| 9. |
- Fassnacht, Martin, et al.
(författare)
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Combination chemotherapy in advanced adrenocortical carcinoma
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 366:23, s. 2189-2197
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment.METHODS:We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival.RESULTS:For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments.CONCLUSIONS:Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival.
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| 10. |
- Harrie, Lars, et al.
(författare)
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Some strategic national initiatives for the Swedish education in the geodata field
- 2014
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Ingår i: Proceedings of the AGILE'2014 International Conference on Geographic Information Science. - : AGILE Digital Editions. - 9789081696043
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Konferensbidrag (refereegranskat)abstract
- This paper describes national cooperation in Sweden launched by its universities and authorities, aimed at improving geodata education. These initiatives have been focused upon providing common access to geodata, the production of teaching materials in Swedish and organizing annual meetings for teachers. We argue that this type of cooperation is vital to providing high quality education for a poorly recognized subject in a country with a relatively small population.
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| 11. |
- Margolskee, Alison, et al.
(författare)
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IMI - oral biopharmaceutics tools project - evaluation of bottom-up PBPK prediction success part 1 : Characterisation of the OrBiTo database of compounds
- 2017
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 598-609
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Tidskriftsartikel (refereegranskat)abstract
- Predicting oral bioavailability (F-oral) is of importance for estimating systemic exposure of orally administered drugs. Physiologically-based pharmacokinetic (PBPK) modelling and simulation have been applied extensively in biopharmaceutics recently. The Oral Biopharmaceutical Tools (OrBiTo) project (Innovative Medicines Initiative) aims to develop and improve upon biopharmaceutical tools, including PBPK absorption models. A large-scale evaluation of PBPK models may be considered the first step. Here we characterise the OrBiTo active pharmaceutical ingredient (API) database for use in a large-scale simulation study. The OrBiTo database comprised 83 APIs and 1475 study arms. The database displayed a median logP of 3.60 (2.40-4.58), human blood-to-plasma ratio of 0.62 (0.57-0.71), and fraction unbound in plasma of 0.05 (0.01-0.17). The database mainly consisted of basic compounds (48.19%) and Biopharmaceutics Classification System class II compounds (55.81%). Median human intravenous clearance was 16.9 L/h (interquartile range: 11.6-43.6 L/h; n = 23), volume of distribution was 80.8 L (54.5-239 L; n = 23). The majority of oral formulations were immediate release (IR: 87.6%). Human Foral displayed a median of 0.415 (0.203-0.724; n = 22) for IR formulations. The OrBiTo database was found to be largely representative of previously published datasets. 43 of the APIs were found to satisfy the minimum inclusion criteria for the simulation exercise, and many of these have significant gaps of other key parameters, which could potentially impact the interpretability of the simulation outcome. However, the OrBiTo simulation exercise represents a unique opportunity to perform a large-scale evaluation of the PBPK approach to predicting oral biopharmaceutics.
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| 12. |
- Nucara, A., et al.
(författare)
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Hardening of the soft phonon in bulk SrTiO3 interfaced with LaAlO3 and SrRuO3
- 2016
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 93:22
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Tidskriftsartikel (refereegranskat)abstract
- The low-temperature softening of the TO1 phonon of SrTiO3 (STO), which determines its incipient ferroelectricity, is known to be partially hindered either in the bulk under strong electric fields, or in thin STO films. Here we show, by terahertz (THz) reflectivity measurements, that a similar effect is produced in bulk STO and at zero static field by ultrathin metallic films on its surface, like a 10-nm-thick film of SrRuO3 (SRO), or the two-dimensional electron system (2DES) present at the interface with LaAlO3. In SRO/STO, the observed hardening is well explained by the depolarizing action of the SRO free electrons which follow adiabatically the ion motion. In LAO/STO, a weaker TO1 hardening could be detected by patterning the 2DES in the form of microstripes and using a polarized THz field parallel (E-) or orthogonal (E-) to the stripes. At 10 K, when TO1 is excited together with the free electrons by E-, its absorbance is harder by about 7 cm-1 than that measured when TO1 is coupled to the plasmon-polariton confined within the stripes, being excited by E-.
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| 13. |
- Reischer, G. H., et al.
(författare)
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Performance Characteristics of qPCR Assays Targeting Human- and Ruminant-Associated Bacteroidetes for Microbial Source Tracking across Sixteen Countries on Six Continents
- 2013
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 47:15, s. 8548-8556
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Tidskriftsartikel (refereegranskat)abstract
- Numerous quantitative PCR assays for microbial fecal source tracking (MST) have been developed and evaluated in recent years. Widespread application has been hindered by a lack of knowledge regarding the geographical stability and hence applicability of such methods beyond the regional level. This study assessed the performance of five previously reported quantitative PCR assays targeting human-, cattle-, or ruminant-associated Bacteroidetes populations on 280 human and animal fecal samples from 16 countries across six continents. The tested cattle-associated markers were shown to be ruminant-associated. The quantitative distributions of marker concentrations in target and nontarget samples proved to be essential for the assessment of assay performance and were used to establish a new metric for quantitative source-specificity. In general, this study demonstrates that stable target populations required for marker-based MST occur around the globe. Ruminant-associated marker concentrations were strongly correlated with total intestinal Bacteroidetes populations and with each other, indicating that the detected ruminant-associated populations seem to be part of the intestinal core microbiome of ruminants worldwide. Consequently tested ruminant-targeted assays appear to be suitable quantitative MST tools beyond the regional level while the targeted human-associated populations seem to be less prevalent and stable, suggesting potential for improvements in human-targeted methods.
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| 16. |
- Weist, P., et al.
(författare)
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Assessing SNP-markers to study population mixing and ecological adaptation in Baltic cod
- 2019
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- Atlantic cod (Gadus morhua) is a species of great ecological and economical importance in the Baltic Sea. Here, two genetically differentiated stocks, the western and the eastern Baltic cod, display substantial mechanical mixing, hampering our understanding of cod ecology and impeding stock assessments and management. Based on whole-genome re-sequencing data from reference samples obtained from the study area, we designed two different panels of Single Nucleotide Polymorphisms markers (SNPs), which take into account the exceptional genome architecture of cod. A minimum panel of 20 diagnostic SNPs and an extended panel (20 diagnostic and 18 biologically informative SNPs, 38 in total) were developed and validated to distinguish unambiguously between the western and the eastern Baltic cod stocks and to enable studies of local adaptation to the specific environment in the Baltic Sea, respectively. We tested both panels on cod sampled from the southern Baltic Sea (n = 603) caught in 2015 and 2016. Genotyping results showed that catches from the mixing zone in the Arkona Sea, were composed of similar proportions of individuals of the western and the eastern stock. Catches from adjacent areas to the east, the Bornholm Basin and Gdansk Deep, were exclusively composed of eastern Baltic cod, whereas catches from adjacent western areas (Belt Sea and Oresund) were composed of western Baltic cod. Interestingly, the two Baltic cod stocks showed strong genetic differences at loci associated with life-history trait candidate genes, highlighting the species' potential for ecological adaptation even at small geographical scales. The minimum and the extended panel of SNP markers presented in this study provide powerful tools for future applications in research and fisheries management to further illuminate the mixing dynamics of cod in the Baltic Sea and to better understand Baltic cod ecology.
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| 17. |
- Wohlfahrt, G., et al.
(författare)
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An ecosystem-scale perspective of the net land methanol flux : synthesis of micrometeorological flux measurements
- 2015
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 15:13, s. 7413-7427
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Tidskriftsartikel (refereegranskat)abstract
- Methanol is the second most abundant volatile organic compound in the troposphere and plays a significant role in atmospheric chemistry. While there is consensus about the dominant role of living plants as the major source and the reaction with OH as the major sink of methanol, global methanol budgets diverge considerably in terms of source/sink estimates, reflecting uncertainties in the approaches used to model and the empirical data used to separately constrain these terms. Here we compiled micrometeorological methanol flux data from eight different study sites and reviewed the corresponding literature in order to provide a first cross-site synthesis of the terrestrial ecosystem-scale methanol exchange and present an independent data-driven view of the land-atmosphere methanol exchange. Our study shows that the controls of plant growth on production, and thus the methanol emission magnitude, as well as stomatal conductance on the hourly methanol emission variability, established at the leaf level, hold across sites at the ecosystem level. Unequivocal evidence for bi-directional methanol exchange at the ecosystem scale is presented. Deposition, which at some sites even exceeds methanol emissions, represents an emerging feature of ecosystem-scale measurements and is likely related to environmental factors favouring the formation of surface wetness. Methanol may adsorb to or dissolve in this surface water and eventually be chemically or biologically removed from it. Management activities in agriculture and forestry are shown to increase local methanol emission by orders of magnitude; however, they are neglected at present in global budgets. While contemporary net land methanol budgets are overall consistent with the grand mean of the micrometeorological methanol flux measurements, we caution that the present approach of simulating methanol emission and deposition separately is prone to opposing systematic errors and does not allow for full advantage to be taken of the rich information content of micrometeorological flux measurements.
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