| 1. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)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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| 2. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 3. |
- Löbel, Martin, et al.
(författare)
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Microstructure and Corrosion Properties of AlCrFeCoNi High-Entropy Alloy Coatings Prepared by HVAF and HVOF
- 2022
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Ingår i: Journal of thermal spray technology (Print). - : Springer. - 1059-9630 .- 1544-1016. ; :1-2, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- High-entropy alloys (HEAs) represent an innovative development approach for new alloy systems. These materials have been found to yield promising properties, such as high strength in combination with sufficient ductility as well as high wear and corrosion resistance. Especially for alloys with a body-centered cubic (bcc) structure, advantageous surface properties have been revealed. However, typical HEA systems contain high contents of expensive or scarce elements. Consequently, applying them as coatings where their use is limited to the surface represents an exciting pathway enabling economical exploitation of their superior properties. Nevertheless, processing conditions strongly influence the resulting microstructure and phase formation, which in turn has a considerable effect on the functional properties of HEAs. In the presented study, microstructural differences between high-velocity oxygen fuel (HVOF) and high-velocity air fuel (HVAF) sprayed coatings of the alloy AlCrFeCoNi are investigated. A metastable bcc structure is formed in both coating processes. Precipitation reactions are suppressed by the rapid solidification during atomization and by the relatively low thermal input during spraying. The coating resistance to corrosive media was investigated in detail, and an improved passivation behavior was observed in the HVAF coatings.
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| 4. |
- Widemann, Thomas, et al.
(författare)
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Venus Evolution Through Time : Key Science Questions, Selected Mission Concepts and Future Investigations
- 2023
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Ingår i: Space Science Reviews. - : SPRINGER. - 0038-6308 .- 1572-9672. ; 219:7
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Forskningsöversikt (refereegranskat)abstract
- In this work we discuss various selected mission concepts addressing Venus evolution through time. More specifically, we address investigations and payload instrument concepts supporting scientific goals and open questions presented in the companion articles of this volume. Also included are their related investigations (observations & modeling) and discussion of which measurements and future data products are needed to better constrain Venus' atmosphere, climate, surface, interior and habitability evolution through time. A new fleet of Venus missions has been selected, and new mission concepts will continue to be considered for future selections. Missions under development include radar-equipped ESA-led EnVision M5 orbiter mission (European Space Agency 2021), NASA-JPL's VERITAS orbiter mission (Smrekar et al. 2022a), NASA-GSFC's DAVINCI entry probe/flyby mission (Garvin et al. 2022a). The data acquired with the VERITAS, DAVINCI, and EnVision from the end of this decade will fundamentally improve our understanding of the planet's long term history, current activity and evolutionary path. We further describe future mission concepts and measurements beyond the current framework of selected missions, as well as the synergies between these mission concepts, ground-based and space-based observatories and facilities, laboratory measurements, and future algorithmic or modeling activities that pave the way for the development of a Venus program that extends into the 2040s (Wilson et al. 2022).
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| 5. |
- Abgrall, N., et al.
(författare)
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The large enriched germanium experiment for neutrinoless double beta decay (LEGEND)
- 2017
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Ingår i: AIP Conference Proceedings. - : Author(s). - 1551-7616 .- 0094-243X. ; 1894
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Konferensbidrag (refereegranskat)abstract
- The observation of neutrinoless double-beta decay (0νββ) would show that lepton number is violated, reveal that neu-trinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of ∼0.1 count /(FWHM·t·yr) in the region of the signal. The current generation 76Ge experiments GERDA and the Majorana Demonstrator, utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0νββ signal region of all 0νββ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale 76Ge experiment. The collaboration aims to develop a phased 0νββ experimental program with discovery potential at a half-life approaching or at 1028 years, using existing resources as appropriate to expedite physics results.
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| 6. |
- Akhmedov, Evgeny K., et al.
(författare)
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Series expansions for three-flavor neutrino oscillation probabilities in matter
- 2004
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Ingår i: Journal of High Energy Physics (JHEP). - : IOP Publishing. - 1126-6708 .- 1029-8479. ; 2004:04, s. 078-
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Tidskriftsartikel (refereegranskat)abstract
- We present a number of complete sets of series expansion formulas for neutrino oscillation probabilities in matter of constant density for three flavors. In particular, we study expansions in the mass hierarchy parameter alpha = Deltam(21)(2)/Deltam(31)(2) and mixing parameter s(13) = sin theta(13) up to second order and expansions only in alpha and only in s(13) up to first order. For each type of expansion we also present the corresponding formulas for neutrino oscillations in vacuum. We perform a detailed analysis of the accuracy of the different sets of series expansion formulas and investigate which type of expansion is most accurate in different regions of the parameter space spanned by the neutrino energy E, the baseline length L, and the expansion parameters alpha and s(13). We also present the formulas for series expansions in alpha and in s(13) up to first order for the case of arbitrary matter density profiles. Furthermore, it is shown that in general all the 18 neutrino and antineutrino oscillation probabilities can be expressed through just two independent probabilities.
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| 7. |
- Buehligen, Franziska, et al.
(författare)
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Analysis of aging in lager brewing yeast during serial repitching
- 2014
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 187, s. 60-70
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Tidskriftsartikel (refereegranskat)abstract
- Serial repitching of brewing yeast inoculates is an important economic factor in the brewing industry, as their propagation is time and resource intensive. Here, we investigated whether replicative aging and/or the population distribution status changed during serial repitching in three different breweries with the same brewing yeast strain but different abiotic backgrounds and repitching regimes with varying numbers of reuses. Next to bud scar numbers the DNA content of the Saccharomyces pastorianus HEBRU cells was analyzed. Gene expression patterns were investigated using low-density microarrays with genes for aging, stress, storage compound metabolism and cell cycle. Two breweries showed a stable rejuvenation rate during serial repitching. In a third brewery the fraction of virgin cells varied, which could be explained with differing wort aeration rates. Furthermore, the number of bud scars per cell and cell size correlated in all 3 breweries throughout all runs. Transcriptome analyses revealed that from the 6th run on, mainly for the cells positive gene expression could be seen, for example up-regulation of trehalose and glycogen metabolism genes. Additionally, the cells' settling in the cone was dependent on cell size, with the lowest and the uppermost cone layers showing the highest amount of dead cells. In general, cells do not progressively age during extended serial repitching.
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| 8. |
- Bölükbas, Deniz, et al.
(författare)
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Organ-Restricted Vascular Delivery of Nanoparticles for Lung Cancer Therapy
- 2020
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Ingår i: Advanced Therapeutics. - : Wiley. - 2366-3987. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticle-based targeted drug delivery holds promise for treatment of cancers. However, most approaches fail to be translated into clinical success due to ineffective tumor targeting in vivo. Here, the delivery potential of mesoporous silica nanoparticles (MSN) functionalized with targeting ligands for epidermal growth factor receptor and C─C chemokine receptor type 2 is explored in lung tumors. The addition of active targeting ligands on MSNs enhances their uptake in vitro but fails to promote specific delivery to tumors in vivo, when administered systemically via the blood or locally to the lung into immunocompetent murine lung cancer models. Ineffective tumor targeting is due to efficient clearance of the MSNs by the phagocytic cells of the liver, spleen, and lung. These limitations, however, are successfully overcome using a novel organ-restricted vascular delivery (ORVD) approach. ORVD in isolated and perfused mouse lungs of Kras-mutant mice enables effective nanoparticle extravasation from the tumor vasculature into the core of solid lung tumors. In this study, ORVD promotes tumor cell-specific uptake of nanoparticles at cellular resolution independent of their functionalization with targeting ligands. Organ-restricted vascular delivery thus opens new avenues for optimized nanoparticles for lung cancer therapy and may have broad applications for other vascularized tumor types.
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| 9. |
- Cam, Henrik, et al.
(författare)
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The complexities of communication at hospital discharge of older patients : a qualitative study of healthcare professionals' views
- 2023
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Ingår i: BMC Health Services Research. - : BioMed Central (BMC). - 1472-6963. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hospital discharge of older patients is a high-risk situation in terms of patient safety. Due to the fragmentation of the healthcare system, communication and coordination between stakeholders are required at discharge. The aim of this study was to explore communication in general and medication information transfer in particular at hospital discharge of older patients from the perspective of healthcare professionals (HCPs) across different organisations within the healthcare system.Methods: We conducted a qualitative study using focus group and individual or group interviews with HCPs (physicians, nurses and pharmacists) across different healthcare organisations in Sweden. Data were collected from September to October 2021. A semi-structured interview guide including questions on current medication communication practices, possible improvements and feedback on suggestions for alternative processes was used. The data were analysed thematically, guided by the systematic text condensation method.Results: In total, four focus group and three semi-structured interviews were conducted with 23 HCPs. Three main themes were identified: 1) Support systems that help and hinder describes the use of support systems in the discharge process to compensate for the fragmentation of the healthcare system and the impact of these systems on HCPs' communication; 2) Communication between two separate worlds depicts the difficulties in communication experienced by HCPs in different healthcare organisations and how they cope with them; and 3) The large number of medically complex patients disrupts the communication reveals how the highly pressurised healthcare system impacts on HCPs' communication at hospital discharge.Conclusions: Communication at hospital discharge is hindered by the fragmented, highly pressurised healthcare system. HCPs are at risk of moral distress when coping with communication difficulties. Improved communication methods at hospital discharge are needed for the benefit of both patients and HCPs.
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| 10. |
- Carsten, Hobohm, et al.
(författare)
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Land Use Change and the Future of Biodiversity
- 2021
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Ingår i: Perspectives for Biodiversity and Ecosystems. - Cham : Springer. - 2214-2827 .- 2214-2835. - 9783030577094 ; , s. 451-483
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This synthesis report is a meta-analysis of perspectives for biodiversity and ecosystems, with a strong focus on human impacts on the environment, and a work order to enable and manage the protection, survival and evolution of all species on Earth. The goal is to protect nature without any further species loss (Zero Extinction). With this report, we assess alarming signals from the environment; determine the needs of threatened biota and the required actions to manage and protect landscapes and ecosystems; and identify some inescapable tendencies, challenges but also possibilities. The story of humans on Earth is at a critical juncture. Human behaviour is inherently dependent on physical and societal relations, including orientation and positioning within the physical environment. There is no single cultural benefit that is independent of provisioning through ecosystem services. Humans are part of the environment, acquire all needs from it and, as such, depend on its integrity and management for life and well-being. Moreover, if human impacts to the environment continue to increase the risk of rebound effects impacting human life and health will increase as well. Whenever a biome, ecosystem, habitat or species is heavily impacted or threatened with irreversible transformation or extinction, prevailing environmental conditions are relevant and should be observed, analysed and remedied as necessary and where possible. Ecology examines the evolutionary, historical and more recent interplay between biological life and the abiotic environment, while the role of social science and the humanities is to question the physical and social landscape, and how and why it should be protected or influenced, e.g. by nature conservation measures under political and economic, ethical and legal considerations. Thus, for all inter-relationships between natural and sociocultural processes, a joint venture in the form of social-ecological thinking is necessary to combine natural sciences and the humanities. With this contribution, we combine ecological knowledge with social science knowledge (s.l.) through the participation of scientists of many different disciplines. We analyse history and current processes to assess risks, threats and possibilities, and call for an array of regulations and measures that can contribute to halting of biodiversity loss and that assist in achieving a sustainable future. Regulations comprise creativity, cultural incentives, social norms, environmental education and economic investments—such as payments for sustainable agriculture, forestry, and fishery; investments in water, soil and air purity; and much clearer and stronger legal restrictions and consequences around waste streams and environmental degradation. Moreover, a gradual change from profit-oriented economies in the short-run to environmentally-sensitive policies that include systematic environmental programmes in the long term might help to decrease pressure on ecosystems and biota. Such economics might also include the real costs of consumerism, including the impacts of particular products on the environment and on human health. The greatest hurdle for the continued existence of many critically endangered species is the impact of widespread anthropogenic-driven change in the usage of water, air and land, and industry intensification in agriculture, aquaculture, forestry, urbanisation, transportation and mining sectors. However, there is not one simple solution to solve these issues. We conclude that many of the current developments have to be adjusted or gradually altered in a step-wise manner, especially with respect to existing sociocultural behaviours. Therefore, various concepts, decisions and measures should be discussed and implemented at all scales from local to supranational and among researchers, practitioners and politicians.
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| 11. |
- Chien, Yin-Hsiu, et al.
(författare)
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Mudd's disease (MAT I/III deficiency) : a survey of data for MAT1A homozygotes and compound heterozygotes
- 2015
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper summarizes the results of a group effort to bring together the worldwide available data on patients who are either homozygotes or compound heterozygotes for mutations in MAT1A. MAT1A encodes the subunit that forms two methionine adenosyltransferase isoenzymes, tetrameric MAT I and dimeric MAT III, that catalyze the conversion of methionine and ATP to S-adenosylmethionine (AdoMet). Subnormal MAT I/III activity leads to hypermethioninemia. Individuals, with hypermethioninemia due to one of the MAT1A mutations that in heterozygotes cause relatively mild and clinically benign hypermethioninemia are currently often being flagged in screening programs measuring methionine elevation to identify newborns with defective cystathionine beta-synthase activity. Homozygotes or compound heterozygotes for MAT1A mutations are less frequent. Some but not all, such individuals have manifested demyelination or other CNS abnormalities. Purpose of the study: The goals of the present effort have been to determine the frequency of such abnormalities, to find how best to predict whether they will occur, and to evaluate the outcomes of the variety of treatment regimens that have been used. Data have been gathered for 64 patients, of whom 32 have some evidence of CNS abnormalities (based mainly on MRI findings), and 32 do not have such evidence. Results and Discussion: The results show that mean plasma methionine concentrations provide the best indication of the group into which a given patient will fall: those with means of 800 mu M or higher usually have evidence of CNS abnormalities, whereas those with lower means usually do not. Data are reported for individual patients for MAT1A genotypes, plasma methionine, total homocysteine (tHcy), and AdoMet concentrations, liver function studies, results of 15 pregnancies, and the outcomes of dietary methionine restriction and/or AdoMet supplementation. Possible pathophysiological mechanisms that might contribute to CNS damage are discussed, and tentative suggestions are put forth as to optimal management.
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| 12. |
- Gibaud, Thomas, et al.
(författare)
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New routes to food gels and glasses
- 2012
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Ingår i: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1364-5498 .- 1359-6640. ; 158, s. 267-284
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Tidskriftsartikel (refereegranskat)abstract
- We describe the possibility to create solid-like protein samples whose structural and mechanical properties can be varied and tailored over an extremely large range in a very controlled way through an arrested spinodal decomposition process. We use aqueous lysozyme solutions as a model globular protein system. A combination of video microscopy, small-angle neutron and X-ray scattering and reverse Monte Carlo modeling is used to characterize the structure of the bicontinuous network with two coexisting phases of a dilute protein solution and a glassy or arrested dense protein backbone at all relevant length scales. Rheological measurements are then used to determine the complex mechanical response of these protein gels as a function of protein concentration and quench temperature. While in particular the origin of the dependence of the mechanical properties on quench depth and concentration is not well understood currently, it seems ultimately connected to the particular bicontinuous structure of the arrested spinodal network created by the interplay between the early stage of a spinodal decomposition and the position of the glass line. We then generalize this behavior and discuss how this could open up new routes to prepare gel-like food systems with adjustable structural and mechanical properties. We present results from a first feasibility study where we use a depletion interaction caused by the addition of small non-adsorbing polymers to suspensions of casein micelles in order to create food gels with tunable structural and mechanical properties through an arrested spinodal decomposition process.
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| 13. |
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| 14. |
- Iaccarino, Corrado, et al.
(författare)
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Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel
- 2024
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Ingår i: Brain & spine. - : Elsevier. - 2772-5294. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance.RESEARCH QUESTION: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems.METHODS: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction."RESULTS: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain."DISCUSSION AND CONCLUSION: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.
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| 15. |
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| 16. |
- Kempen, Thomas, et al.
(författare)
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Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients' Use of Health Care : A Cluster Randomized Clinical Trial
- 2021
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Suboptimal use of medications is a leading cause of health care–related harm. Medication reviews improve medication use, but evidence of the possible benefit of inpatient medication review for hard clinical outcomes after discharge is scarce.Objective: To study the effects of hospital-based comprehensive medication reviews (CMRs), including postdischarge follow-up of older patients’ use of health care resources, compared with only hospital-based reviews and usual care.Design, Setting, and Participants: The Medication Reviews Bridging Healthcare trial is a cluster randomized crossover trial that was conducted in 8 wards with multiprofessional teams at 4 hospitals in Sweden from February 6, 2017, to October 19, 2018, with 12 months of follow-up completed December 6, 2019. The study was prespecified in the trial protocol. Outcome assessors were blinded to treatment allocation. In total, 2644 patients aged 65 years or older who had been admitted to 1 of the study wards for at least 1 day were included. Data from the modified intention-to-treat population were analyzed from December 10, 2019, to September 9, 2020.Interventions: Each ward participated in the trial for 6 consecutive 8-week periods. The wards were randomized to provide 1 of 3 treatments during each period: CMR, CMR plus postdischarge follow-up, and usual care without a clinical pharmacist.Main Outcomes and Measures: The primary outcome measure was the incidence of unplanned hospital visits (admissions plus emergency department visits) within 12 months. Secondary outcomes included medication-related admissions, visits with primary care clinicians, time to first unplanned hospital visit, mortality, and costs of hospital-based care.Results: Of the 2644 participants, 7 withdrew after inclusion, leaving 2637 for analysis (1357 female [51.5%]; median age, 81 [interquartile range, 74-87] years; median number of medications, 9 [interquartile range, 5-13]). In the modified intention-to-treat analysis, 922 patients received CMR, 823 received CMR plus postdischarge follow-up, and 892 received usual care. The crude incidence rate of unplanned hospital visits was 1.77 per patient-year in the total study population. The primary outcome did not differ between the intervention groups and usual care (adjusted rate ratio, 1.04 [95% CI, 0.89-1.22] for CMR and 1.15 [95% CI, 0.98-1.34] for CMR plus postdischarge follow-up). However, CMR plus postdischarge follow-up was associated with an increased incidence of emergency department visits within 12 months (adjusted rate ratio, 1.29; 95% CI, 1.05-1.59) compared with usual care. There were no differences between treatment groups regarding other secondary outcomes.Conclusions and Relevance: In this study of older hospitalized patients, CMR plus postdischarge follow-up did not decrease the incidence of unplanned hospital visits. The findings do not support the performance of hospital-based CMRs as conducted in this trial. Alternative forms of medication reviews that aim to improve older patients’ health outcomes should be considered and subjected to randomized clinical trials.
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| 17. |
- Kempen, Thomas, et al.
(författare)
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Intervention fidelity and process outcomes of medication reviews including post-discharge follow-up in older hospitalized patients : Process evaluation of the MedBridge trial.
- 2020
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Ingår i: Journal of Clinical Pharmacy and Therapeutics. - : Hindawi Limited. - 0269-4727 .- 1365-2710. ; 45:5, s. 1021-1029
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Tidskriftsartikel (refereegranskat)abstract
- WHAT IS KNOWN AND OBJECTIVE: Drug-related problems (DRPs) are a growing healthcare burden worldwide. In an ongoing cluster-randomized controlled trial in Sweden (MedBridge), comprehensive medication reviews (CMRs) including post-discharge follow-up have been conducted in older hospitalized patients to prevent and solve DRPs. As part of a process evaluation of the MedBridge trial, this study aimed to assess the intervention fidelity and process outcomes of the trial's interventions.METHODS: For intervention delivery, the percentage of patients that received intervention components was calculated per study group. Process outcomes, measured in about one-third of all intervention patients, included the following: the number of identified medication discrepancies, DRPs and recommendations to solve DRPs, correction rate of discrepancies, and implementation rate of recommendations.RESULTS AND DISCUSSION: The MedBridge trial included 2637 patients (mean age: 81 years). The percentage of intervention patients (n = 1745) that received the intended intervention components was 94%-98% during admission, and 40%-81% upon and after discharge. The percentage of control patients (n = 892) that received at least one unintended intervention component was 15%. On average, 1.1 discrepancies and 2.0 DRPs were identified in 652 intervention patients. The correction and implementation rates were 79% and 73%, respectively. Stop medication was the most frequently implemented recommendation (n = 293) and 77% of the patients had at least one corrected discrepancy or implemented recommendation.WHAT IS NEW AND CONCLUSION: The intervention fidelity within the MedBridge trial was high for CMRs during hospital stay and lower for intervention components upon and after discharge. The high prevalence of corrected discrepancies and implemented recommendations may explain potential effects of CMRs in the MedBridge trial.
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| 18. |
- Kempen, Thomas, et al.
(författare)
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Medication Reviews Bridging Healthcare (MedBridge) : Study protocol for a pragmatic cluster-randomised crossover trial
- 2017
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Ingår i: Contemporary Clinical Trials. - : Elsevier BV. - 1551-7144 .- 1559-2030. ; 61, s. 126-132
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mismanaged prescribing and use of medication among elderly puts major pressure on current healthcare systems. Performing a medication review, a structured critical examination of a patient's medications, during hospital stay with active follow-up into primary care could optimise treatment benefit and minimise harm. However, a lack of high quality evidence inhibits widespread implementation. This manuscript describes the rationale and design of a pragmatic cluster-randomised, crossover trial to fulfil this need for evidence.AIM: To study the effects of hospital-initiated comprehensive medication reviews, including active follow-up, on elderly patients' healthcare utilisation compared to 1) usual care and 2) solely hospital based reviews.DESIGN: Multicentre, three-treatment, replicated, cluster-randomised, crossover trial.SETTING: 8 wards with a multidisciplinary team within 4 hospitals in 3 Swedish counties.PARTICIPANTS: Patients aged 65years or older, admitted to one of the study wards.EXCLUSION CRITERIA: Palliative stage; residing in other than the hospital's county; medication review within the last 30days; one-day admission.INTERVENTIONS: 1, comprehensive medication review during hospital stay; 2, same as 1 with the addition of active follow-up into primary care; 3, usual care.PRIMARY OUTCOME MEASURE: Incidence of unplanned hospital visits during a 12-month follow-up period.DATA COLLECTION AND ANALYSES: Extraction and collection from the counties' medical record system into a GCP compliant electronic data capture system. Intention-to-treat-analyses using hierarchical models.RELEVANCE: This study has a high potential to show a reduction in elderly patients' morbidity, contributing to more sustainable healthcare in the long run.
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| 19. |
- Kempen, Thomas, et al.
(författare)
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Risk factors for and preventability of drug-related hospital revisits in older patients: A post-hoc analysis of a randomized clinical trial
- 2023
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Ingår i: British Journal of Clinical Pharmacology. - : WILEY. - 0306-5251 .- 1365-2125. ; 89:5, s. 1575-1587
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Tidskriftsartikel (refereegranskat)abstract
- AimThe aims of this study were (1) to identify older patients risk factors for drug-related readmissions and (2) to assess the preventability of older patients drug-related revisits. MethodsPost hoc analysis of a randomized clinical trial with patients aged >= 65 years at eight wards within four hospitals in Sweden. (1) The primary outcome was risk factors for drug-related readmission within 12 months post-discharge. A Cox proportional hazards model was made with sociodemographic and clinical baseline characteristics. (2) Four hundred trial participants were randomly selected and their revisits (admissions and emergency department visits) were assessed to identify potentially preventable drug-related revisits, related diseases and causes. Results(1) Among 2637 patients (median age 81 years), 582 (22%) experienced a drug-related readmission within 12 months. Sixteen risk factors (hazard ratio >1, P < 0.05) related to age, previous hospital visits, medication use, multimorbidity and cardiovascular, liver, lung and peptic ulcer disease were identified. (2) The 400 patients experienced a total of 522 hospital revisits, of which 85 (16%) were potentially preventable drug-related revisits. The two most prevalent related diseases were heart failure (n = 24, 28%) and chronic obstructive pulmonary disease (n = 13, 15%). The two most prevalent causes were inadequate treatment (n = 23, 27%) and insufficient or no follow-up (n = 22, 26%). Conclusion(1) Risk factors for drug-related readmissions in older hospitalized patients were age, previous hospital visits, medication use and multiple diseases. (2) Potentially preventable drug-related hospital revisits are common and might be prevented through adequate pharmacotherapy and continuity of care in older patients with cardiovascular or lung disease.
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| 20. |
- Költringer, Chiara, et al.
(författare)
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Palaeoenvironmental implications from Lower Volga loess - Joint magnetic fabric and multi-proxy analyses
- 2021
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Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 267, s. 107057-
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic fabric (MF) investigations complemented by geochemical and grain surface analyses of the understudied and controversial marine isotope stage (MIS) 5 b, 4 and 3 loess deposits in the Lower Volga region, Russia show that the material has been transported and deposited by wind and to a large extent experienced post-depositional reworking. Grain surface features suggest that the material was glacially ground and fluvially transported prior to final aeolian deposition as loess. Secondary magnetic fabrics in the loess reveal pedogenic and cryogenic processes and a generally cold environment with brief shifts to warmer climate during late MIS 5 and MIS 3. Palaeowind reconstructions derived from preserved primary aeolian MF, indicate locally influenced westerly and north-westerly flow as part of a wider scale westerly wind pattern, similar to modern day winter conditions. We suggest that the climate of the last glacial in the Northern Caspian Lowland was cold and dry, with higher windspeeds and less variability during MIS 4 compared to MIS 3.
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| 21. |
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| 22. |
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| 23. |
- Költringer, Chiara, et al.
(författare)
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Quaternary sediment sources and loess transport pathways in the Black Sea - Caspian Sea region identified by detrital zircon U-Pb geochronology
- 2022
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Ingår i: Global and Planetary Change. - : Elsevier. - 0921-8181 .- 1872-6364. ; 209
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Tidskriftsartikel (refereegranskat)abstract
- Constraining the controls on the distribution of sediment at a continental scale is a critical step in understandinglong-term landscape and climate evolution. In particular, understanding of the role of rivers in wider sedimentrouting and impacts on aeolian loess formation on a continental scale remains limited. Extensive Quaternaryloess deposits are present on the East European Plain and in the Black Sea - Caspian Sea region and are associatedwith major rivers draining numerous surrounding cratonic and orogenic hinterland areas. Coupled with this,complex changes in local and global sea level have affected the extent and drainage of the Caspian Sea and theBlack Sea, and Quaternary glaciations have impinged on the northern margin of the East European Plain. Thissuggests that sediment routing and loess formation may show complex patterns and controls. Here, we applyU–Pb dating of detrital zircons from fluvial, marine and aeolian (dominantly loess) sedimentary records on theEast European Plain and in the Black Sea - Caspian Sea region. This shows a strong control of large rivers on thedistribution of sediments at a continental scale in the region, through long-distance transport of several 1000 km,sourced from continental and mountain glacier areas prior to marine or atmospheric reworking and trans-portation. Strong spatial variability in zircon U–Pb data from loess deposits on the East European Plain revealsmultiple diverse sources to the different individual loess sections, whereas no significant temporal variability inloess source is detected during the Late Pleistocene of the Lower Volga loess in South Russia. While the sedimentsupply from glacial areas via rivers plays an important role for the provenance of East European Plain loessdeposits, our data indicate that the stark spatial diversity in loess provenance on the East European Plain is oftendriven by the input of multiple local sources. Similar to the loess, marine sediments from different basins of theBlack Sea and the Caspian Sea also show significant spatial variability. This variability is controlled by the ba-thymetry of the seas, leading to sedimentary intermixing by sea currents within, but not between differentseparated sea basins. A direct comparison of marine and aeolian sediments at the same depositional site suggeststhat although loess and marine sediments are both dominantly sourced from river sediments containing fartravelled sedimentary material, local sources play a more important role in many loess deposits.
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| 24. |
- Lindner, Philip, et al.
(författare)
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Cognitive flexibility does not predict symptom reduction in Internet interventions
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- PURPOSE: Little is known about whether individual differences in executive functions predict outcomes after Internet-delivered psychological treatments. We hypothesized that learning and utilizing skills taught in treatment is reliant on cognitive flexibility, as measurable by perseverative errors (PE) on the 64-card Wisconsin Card Sorting Test (WCST). We tested this by correlating PE scores with symptom reduction following treatment for social anxiety disorder (n=116), depression (n=42) and tinnitus discomfort (n=28). METHOD: In all groups, the WCST was administered online prior to treatment and partial correlation (controlling for age) were calculated between PE and percentage symptom reduction on the respective primary outcome measure. RESULTS: Number of PE did not correlate with pre-treatment symptom scores in any group. There was no generic association between symptom reduction and PE, and, after outlier removal, no group-specific associations either. CONCLUSIONS: Lower cognitive flexibility does not appear to impede symptom reduction in Internet-delivered psychological treatments.
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| 25. |
- Lindner, Philip, et al.
(författare)
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Does cognitive flexibility predict treatment gains in Internet-delivered psychological treatment of social anxiety disorder, depression, or tinnitus?
- 2016
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the individual factors that predict outcomes in Internet-administered psychological treatments. We hypothesized that greater cognitive flexibility (i.e. the ability to simultaneously consider several concepts and tasks and switch effortlessly between them in response to changes in environmental contingencies) would provide a better foundation for learning and employing the cognitive restructuring techniques taught and exercised in therapy, leading to greater treatment gains. Participants in three trials featuring Internet-administered psychological treatments for depression (n = 36), social anxiety disorder (n = 115) and tinnitus (n = 53) completed the 64-card Wisconsin Card Sorting Test (WCST) prior to treatment. We found no significant associations between perseverative errors on the WCST and treatment gains in any group. We also found low accuracy in the classification of treatment responders. We conclude that lower cognitive flexibility, as captured by perseverative errors on the WCST, should not impede successful outcomes in Internet-delivered psychological treatments.
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| 26. |
- Lindner, Thomas, et al.
(författare)
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Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.
- 2023
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Ingår i: Magnetic Resonance in Medicine. - : John Wiley & Sons. - 0740-3194 .- 1522-2594. ; 89:5, s. 2024-2047
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Tidskriftsartikel (refereegranskat)abstract
- This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review.
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| 27. |
- Lindner, Thomas W, et al.
(författare)
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A pilot study of angiotensin converting enzyme (ACE) genotype and return of spontaneous circulation following out-of-hospital cardiac arrest.
- 2014
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Ingår i: Open heart. - : BMJ. - 2053-3624. ; 1:1, s. e000138-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In the last few years the genetic influence on health and disease outcome has become more apparent. The ACE genotype appears to play a significant role in the pathophysiology of several disease processes. This pilot study aims at showing the feasibility to examine the genetic influence of the ACE genotype on return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA).METHODS: We performed a prospective observational study of all OHCAs of presumed cardiac origin in a well-defined population. We collected prehospital blood samples for the determination of ACE genotype and used this information together with Utstein template parameters in a multivariable analysis to examine the relationship between ROSC and ACE genotype.RESULTS: We collect blood samples in 156 of 361 patients with OHCA of presumed cardiac origin, 127 samples were analysed (mean age 67 years, 86% male, 79% witnessed OHCA, 80% bystander CPR, 62% had a shockable rhythm, ROSC 77%). Distribution of the ACE gene polymorphisms: insertion polymorphism (II) n=22, 17%, insertion/deletion polymorphism (ID) n=66, 52% and deletion polymorphism (DD) n=39, 31%. We found no significant association between ACE II vs ACE DD/DI and ROSC (OR 1.72; CI 0.52 to 5.73; p=0.38). Other ACE genotype groupings (II/ID vs DD or II vs DD) did not change the overall finding of lack of impact of ACE genotype on ROSC.CONCLUSIONS: This pilot study did not indicate a significant association between ACE gene polymorphism and ROSC. However, it has demonstrated that prehospital genetic studies including blood sampling are feasible and ethically acceptable.
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| 28. |
- Moore, Keith J M, et al.
(författare)
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Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications
- 2021
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Ingår i: Journal of Biomolecular Techniques. - : Association of Biomolecular Resource Facilities. - 1524-0215 .- 1943-4731. ; 32:3, s. 228-275
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Forskningsöversikt (refereegranskat)abstract
- As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.
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| 29. |
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| 30. |
- Sinadinovic, Kristina, et al.
(författare)
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Guided web-based treatment program for reducing cannabis use : a randomized controlled trial
- 2020
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Ingår i: Addiction science & clinical practice. - : Springer Science and Business Media LLC. - 1940-0632 .- 1940-0640. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to investigate the effects of a web-based treatment program with therapist guidance for adults and adolescents with regular cannabis use from the general population.Methods: A double blinded randomized controlled trial with a parallel group design was conducted (intervention group n = 151, wait-list control group n = 152). Follow-up 12 weeks from treatment commencement of a 13-module intervention. The primary outcome was frequency of cannabis use. Time by group interaction effects were modeled using generalized estimated equations and the instrumental variable approach was used to estimate the effect of intervention adherence.Results: At follow-up, the intention to treat (ITT) analyses did not show any significant time by group effects. A significant association between intervention adherence and scores on the cannabis abuse screening test (CAST) was found. Secondary analysis excluding participants who had received other professional help revealed time by group effects for secondary outcomes gram cannabis consumed past week, number of dependency criteria and CAST score. Due to methodological limitations, these latter results should be interpreted with caution.Conclusions: In this study we did not find a web-based treatment program with therapist guidance to be more effective than a waiting-list in reducing frequency of cannabis use.Trial registration: The trial was pre-registered at ClinicalTrials.gov (NCT02408640) April 3, 2015
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| 31. |
- Unterluggauer, Hermann, et al.
(författare)
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Identification of Hsc70 as target for AGE modification in senescent human fibroblasts.
- 2009
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Ingår i: Biogerontology. - : Springer Science and Business Media LLC. - 1389-5729 .- 1573-6768. ; 10:3, s. 299-309
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Tidskriftsartikel (refereegranskat)abstract
- Cellular senescence is known as a potent mechanism of tumor suppression, and cellular senescence in vitro also reflects at least some features of aging in vivo. The Free Radical Theory of aging suggests that reactive oxygen species are important causative agents of aging and cellular senescence. Besides damage of nucleic acids and lipids, also oxidative modifications of proteins have been described as potential causative events in the senescence response. However, the identity of protein targets for post-translational modifications in senescent cells has remained unclear. In the present communication, we analyzed the occurrence of oxidative posttranslational modifications in senescent human endothelial cells and dermal fibroblasts. We found a significant increase in the level of protein carbonyls and AGE modification with senescence in both cell types. Using 2D-Gel electrophoresis and Western Blot we found that heat shock cognate protein 70 is a bona fide target for AGE modification in human fibroblasts.
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| 32. |
- Weise, Anja, et al.
(författare)
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High-throughput sequencing of microdissected chromosomal regions.
- 2010
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 18:4, s. 457-62
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Tidskriftsartikel (refereegranskat)abstract
- The linkage of disease gene mapping with DNA sequencing is an essential strategy for defining the genetic basis of a disease. New massively parallel sequencing procedures will greatly facilitate this process, although enrichment for the target region before sequencing remains necessary. For this step, various DNA capture approaches have been described that rely on sequence-defined probe sets. To avoid making assumptions on the sequences present in the targeted region, we accessed specific cytogenetic regions in preparation for next-generation sequencing. We directly microdissected the target region in metaphase chromosomes, amplified it by degenerate oligonucleotide-primed PCR, and obtained sufficient material of high quality for high-throughput sequencing. Sequence reads could be obtained from as few as six chromosomal fragments. The power of cytogenetic enrichment followed by next-generation sequencing is that it does not depend on earlier knowledge of sequences in the region being studied. Accordingly, this method is uniquely suited for situations in which the sequence of a reference region of the genome is not available, including population-specific or tumor rearrangements, as well as previously unsequenced genomic regions such as centromeres.
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| 33. |
- Wunderer, Julia, et al.
(författare)
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A mechanism for temporary bioadhesion
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 116:10, s. 4297-4306
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Tidskriftsartikel (refereegranskat)abstract
- The flatworm Macrostomum lignano features a duo-gland adhesive system that allows it to repeatedly attach to and release from substrates in seawater within a minute. However, little is known about the molecules involved in this temporary adhesion. In this study, we show that the attachment of M. lignano relies on the secretion of two large adhesive proteins, M. lignano adhesion protein 1 (Mlig-ap1) and Mlig-ap2. We revealed that both proteins are expressed in the adhesive gland cells and that their distribution within the adhesive footprints was spatially restricted. RNA interference knockdown experiments demonstrated the essential function of these two proteins in flatworm adhesion. Negatively charged modified sugars in the surrounding water inhibited flatworm attachment, while positively charged molecules impeded detachment. In addition, we found that M. lignano could not adhere to strongly hydrated surfaces. We propose an attachment-release model where Mlig-ap2 attaches to the substrate and Mlig-ap1 exhibits a cohesive function. A small negatively charged molecule is secreted that interferes with Mlig-ap1, inducing detachment. These findings are of relevance for fundamental adhesion science and efforts to mitigate biofouling. Further, this model of flatworm temporary adhesion may serve as the starting point for the development of synthetic reversible adhesion systems for medicinal and industrial applications.
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| 34. |
- Zanne, Amy E, et al.
(författare)
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Fungal functional ecology: bringing a trait-based approach to plant-associated fungi.
- 2020
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Ingår i: Biological reviews of the Cambridge Philosophical Society. - : Wiley. - 1469-185X .- 1464-7931. ; 95:2, s. 409-433
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Tidskriftsartikel (refereegranskat)abstract
- Fungi play many essential roles in ecosystems. They facilitate plant access to nutrients and water, serve as decay agents that cycle carbon and nutrients through the soil, water and atmosphere, and are major regulators of macro-organismal populations. Although technological advances are improving the detection and identification of fungi, there still exist key gaps in our ecological knowledge of this kingdom, especially related to function. Trait-based approaches have been instrumental in strengthening our understanding of plant functional ecology and, as such, provide excellent models for deepening our understanding of fungal functional ecology in ways that complement insights gained from traditional and -omics-based techniques. In this review, we synthesize current knowledge of fungal functional ecology, taxonomy and systematics and introduce a novel database of fungal functional traits (FunFun ). FunFun is built to interface with other databases to explore and predict how fungal functional diversity varies by taxonomy, guild, and other evolutionary or ecological grouping variables. To highlight how a quantitative trait-based approach can provide new insights, we describe multiple targeted examples and end by suggesting next steps in the rapidly growing field of fungal functional ecology.
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| 35. |
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