| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
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| 3. |
- Zhang, Renyun, et al.
(författare)
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Soap-film coating : High-speed deposition of multilayer nanofilms
- 2013
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Ingår i: Scientific Reports. - Nature Publishing Group : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. Art. no. 1477-
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Tidskriftsartikel (refereegranskat)abstract
- The coating of thin films is applied in numerous fields and many methods are employed for the deposition of these films. Some coating techniques may deposit films at high speed; for example, ordinary printing paper is coated with micrometre-thick layers of clay at a speed of tens of meters per second. However, to coat nanometre thin films at high speed, vacuum techniques are typically required, which increases the complexity of the process. Here, we report a simple wet chemical method for the high-speed coating of films with thicknesses at the nanometre level. This soap-film coating technique is based on forcing a substrate through a soap film that contains nanomaterials. Molecules and nanomaterials can be deposited at a thickness ranging from less than a monolayer to several layers at speeds up to meters per second. We believe that the soap-film coating method is potentially important for industrial-scale nanotechnology.
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| 4. |
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| 5. |
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| 6. |
- Burman, Joachim, et al.
(författare)
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Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis : the Swedish experience
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - London, United Kingdom : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 85:10, s. 1116-1121
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.
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| 7. |
- Drevinge, Christina, 1983, et al.
(författare)
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Perilipin 5 is protective in the ischemic heart
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
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Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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| 8. |
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| 9. |
- Johansson, Per, 1973, et al.
(författare)
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Using VMEA to Facilitate the Preparation of Robust Design Experimentation
- 2005
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Ingår i: Proceedings of the 8th International Conference on Quality Management for Organisational and Regional Development (QMOD). - 8890209410 ; Palermo:June 29 - July 1, s. 635-640
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Konferensbidrag (refereegranskat)abstract
- In this paper, we investigate the possibility to facilitate the preparation of robust design experiments with the help of Variation Mode and Effect Analysis (VMEA). In the VMEA procedure, product characteristics important from a variation point of view are identified and assessed along with sources of variation affecting them. As a result, a variation risk priority number is calculated directing our attention to those areas that are most vulnerable to the sources of variation. As information about the sources of variation is valuable from a robust design point of view, the results of a VMEA can serve as a valuable input for preparing a robust design experiment. The variation risk priority numbers provide a means of prioritizing subsequent activities and thus focusing efforts to areas where they are most needed from a robust design standpoint.
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| 10. |
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| 11. |
- Ali, Muhammad, et al.
(författare)
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Leveraging large multi-center cohorts of Alzheimer disease endophenotypes to understand the role of Klotho heterozygosity on disease risk.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- Two genetic variants in strong linkage disequilibrium (rs9536314 and rs9527025) in the Klotho (KL) gene, encoding a transmembrane protein, implicated in longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively normal participants who are APOE ε4 carriers. Specifically, the participants heterozygous for this variant (KL-SVHET+) showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+ has been suggested against amyloid burden for cognitively normal participants, potentially mediated via the regulation of redox pathways. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we performed a well-powered association analysis between KL-VSHET+ and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aβ42 levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau181; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+ status with biomarkers for brain amyloidosis (e.g., CSF Aβ positivity; odds ratio [OR] = 0.67 [95% CI, 0.55-0.78], β = 0.72, p = 0.007) and tau pathology (e.g., biomarker positivity for CSF Tau; OR = 0.39 [95% CI, 0.19-0.77], β = -0.94, p = 0.007, and pTau; OR = 0.50 [95% CI, 0.27-0.96], β = -0.68, p = 0.04) in cognitively normal participants, 60-80 years old, who are APOE e4-carriers. Our work supports previous findings, suggesting that the KL-VSHET+ on an APOE ε4 genotype background may modulate Aβ and tau pathology, thereby lowering the intensity of neurodegeneration and incidence of cognitive decline in older controls susceptible to AD.
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| 12. |
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| 13. |
- Andersson Granberg, Tobias, 1973-, et al.
(författare)
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Plattform för analys av förmågan att hantera händelser med avseende på ett förändrat klimat (PAKT)
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- För att kunna hantera framtida klimatrelaterade händelser behöver samhällets beredskap anpassas och sannolikt utökas. Kunskapsläget över vilken förmåga som behövs för att hantera risker i ett förändrat klimat behöver sammanställas och framtida behov behöver jämföras mot nuvarande beredskapsnivåer för att identifiera lämpliga åtgärder. En analys behöver göras kring eventuella brister, utifrån vilken åtgärder sedan kan prioriteras och vidtas avseende olika delar i förmågan att hantera händelser, bland annat avseende tillhandahållande av statliga förstärkningsresurser. Denna studie analyserar vilken systematik som kan vara aktuell för att möjliggöra sådana analyser och utredningar.Studiens övergripande syfte är att ge förslag kring hur bedömningar kan göras om framtidens behov av statliga förstärkningsresurser i syfte att möta framtidens klimatrelaterade risker. Detta inkluderar en sammanställning av kunskapsläget kring risker och scenarion avseende framtida naturhändelser utifrån ett klimatförändringsperspektiv, med information om var mer kunskap kan hittas. Det inkluderar också att titta på metoder för att dels analysera behov av förmåga på olika nivåer att hantera de klimatrelaterade riskerna och dels hur dimensionering av förmåga kan göras för att möta behovet.Studien består av två delar. I del 1 ges en sammanställning av kunskapsläget om riskbilder och scenarion i Sverige vad gäller framtida naturhändelser utifrån ett klimatförändringsperspektiv och tidsperioden fram till ca år 2100. I del 2 presenteras initialt ett konceptuellt ramverk för kartläggning av beredskap uppdelat i fyra huvuddomäner: Behov, Resurs, Styrning och Beroenden. Baserat på ramverket presenteras därefter en metodik för att analysera samhällets förmåga att hantera framtida händelser i ett förändrat klimat. För att kunna identifiera en lämplig framtida beredskapsnivå, behöver samhällets förmåga att hantera händelser gentemot en framtida riskbild analyseras. Del 2 fokuserar på hur relevanta myndigheter ska kunna gå tillväga för att göra en sådan analys som slutligen kan utgöra beslutsunderlag avseende framtida beredskap. Avslutningsvis ges ett exempel på hur metoden kan användas där händelsen skogsbrand, av omfattningen att nationella förstärkningsresurser i form av MSBs upphandlade helikoptrar och flygplan för skogsbrandbekämpning kan bli aktuella att nyttja, utgör själva händelsen.
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| 14. |
- Bressner, Thomas A.H., et al.
(författare)
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Cell Partitioning Antenna System Performance in Multi-User Scenarios for mmWave Communications
- 2021
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Ingår i: IEEE Access. - 2169-3536 .- 2169-3536. ; 9, s. 127141-127149
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Tidskriftsartikel (refereegranskat)abstract
- Fixed-beam, high-gain antenna systems can be used for a finer partitioning of the currently used cell-sectoring. This partitioning has the benefit of reducing the number of users seen per antenna beam, which reduces interference. Furthermore, the high antenna gain allows for a high effective isotropic radiated power while keeping the transmit power low. In this paper, we study the performance of such a fixed-beam, high gain antenna system design for millimeter-wave mobile communications. The antenna system is designed to keep the inter-sector interference in a multi-site scenario low. The performance is analyzed for single- and multi-user environments. In single-input single-output mode, the 50th percentile of the signal-to-interference-plus-noise ratio lies between 12.5 dB to 39.7 dB if 3 to 0 interferers are present, respectively. For multiple-input multiple-output transmission using zero-forcing, the signal-to-interference-plus-noise ratio increases and the 50th percentile ranges from 36.1 dB to 43.3 dB if 3 to 0 interferes are present, respectively. By using maximum ratio transmission, the best performance is achieved with no interferers present, while a plunge in performance is observed with interferers. Furthermore, the study revealed that the narrow beam antenna system can also provide a clear signal separation for small spatial separations. In the given example, the signal-to-interference-plus-noise ratio is larger than 32.1 dB with 11 active antenna elements, where 2.8 meters separate the users. Hence, the paper shows that the cell-partitioning antenna systems provide coverage in the desired area while keeping the inter-sector interference low, and the considered transmission techniques can be used for situation optimized mobile communication links.
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| 15. |
- Bude, R. X.F., et al.
(författare)
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A System-Performance-Based Comparison of Sparse Regular and Irregular Antenna Arrays for Millimeter-Wave Multi-User MIMO Base Stations
- 2022
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Ingår i: Electronics (Switzerland). - : MDPI AG. - 2079-9292. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- A system-level study was conducted that evaluated the system performance of various dense and sparse antenna array configurations for application in millimeter-wave multi-user multiple-input multiple-output base stations. The performance was evaluated by investigating the probability that a user experiences an outage when a zero-forcing pre-coder is used in a random line of sight scenario. This paper shows that the outage probability significantly decreased when irregular sparse arrays were used rather than regular sparse or regular dense arrays. A re-configurable linear array was designed and realized as a demonstrator. It used 3D-printed aluminum box horn antenna elements that had wide scanning range in the azimuthal plane and a small scanning range in the elevation plane. For the demonstrator, it was shown that the outage probability was reduced from 3.85% to 0.64% by moving from a sparse regularly spaced array to a sparse randomly spaced array. This amounted to an improvement of a factor of six. The sparse topology allowed for the usage of large antenna elements that had an increased gain and still achieved wide-angle scanning, while reducing mutual coupling to a minimum.
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| 16. |
- Buvall, Lisa, 1976, et al.
(författare)
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Orellanine specifically targets renal clear cell carcinoma
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:53, s. 91085-91098
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney, accounts for approximately 85% of kidney cancers and causes over 140,000 annual deaths worldwide. In the last decade, several new therapies have been identified for treatment of metastatic RCC. Although these therapies increase survival time compared to standard care, none of them has curative properties. The nephrotoxin orellanine specifically targets proximal tubular epithelial cells, leaving other organs unaffected. We therefore hypothesized that the selective toxicity of orellanine extends to clear cell RCC (ccRCC) cells since they emanate from proximal tubular cells. Orellanine would thus target both primary and metastatic ccRCC in vitro and in vivo. We found that orellanine induces dose-dependent cell death in proximal tubular cells and in all ccRCC cells tested, both primary and cell lines, with no toxicity detected in control cells. The toxic action of orellanine involve decreased protein synthesis, disrupted cell metabolism and induction of apoptosis. In nude rats carrying human ccRCC xenografts, brief orellanine treatment eliminated more than 90% of viable tumor mass compared to control rats. This identifies orellanine as a potential treatment concept for ccRCC patients on dialysis, due to its unique selective toxicity towards ccRCC.
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| 17. |
- Ekstrand, Matias, et al.
(författare)
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Depletion of ATP and glucose in advanced human atherosclerotic plaques
- 2017
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Ingår i: PLoS One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Severe hypoxia develops close to the necrotic core of advanced human atherosclerotic plaques, but the energy metabolic consequences of this hypoxia are not known. In animal models, plaque hypoxia is also associated with depletion of glucose and ATP. ATP depletion may impair healing of plaques and promote necrotic core expansion. To investigate if ATP depletion is present in human plaques, we analyzed the distribution of energy metabolites (ATP, glucose, glycogen and lactate) in intermediate and advanced human plaques.Snap frozen carotid endarterectomies from 6 symptomatic patients were analyzed. Each endarterectomy included a large plaque ranging from the common carotid artery (CCA) to the internal carotid artery (ICA). ATP, glucose, and glycogen concentrations were lower in advanced (ICA) compared to intermediate plaques (CCA), whereas lactate concentrations were higher. The lowest concentrations of ATP, glucose and glycogen were detected in the perinecrotic zone of advanced plaques.Our study demonstrates severe ATP depletion and glucose deficiency in the perinecrotic zone of human advanced atherosclerotic plaques. ATP depletion may impair healing of plaques and promote disease progression.
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| 18. |
- Elfsberg, Jenny, 1973-, et al.
(författare)
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How Covid-19 Enabled a Global Student Design Team to Achieve Breakthrough Innovation
- 2021
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Ingår i: Proceedings of the Design Society 2021. - : Cambridge University Press. ; , s. 1705-1714
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Konferensbidrag (refereegranskat)abstract
- This is a qualitative single case study of a geographically distributed student team that experienced a quite different graduate course, compared to previous year's. This was due to the restrictions placed upon them following coronavirus lockdowns. With already ongoing research, and continuous development of the course, the authors had documented individual reflections and identified patterns and behaviours that seemingly determined the quality of the end result, as well as the students expectations and experiences. Semi-structured interviews, surveys and the author's individual reflection notes were already in place as part of the larger research scope and when the student team during the covid-19 year showed unexpected performance and results, the authors decided to pause the larger research scope and focus on this unique single case and capture those learnings. Not knowing how the Covid-19 situation evolves and leaning on insights from previous years, as well as this unique year, the aim with this paper is to describe the unique Covid-19 year amd share knowledge that can help improve and evolve the development of this longlived collaborative graduate student course, and other similar distributed team contexts.
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| 19. |
- Elfsberg, Jenny, 1973-
(författare)
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Innovation Engineering in Practice : Bridging Exploration and Exploitation in Large Manufacturing Incumbents
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis discusses how large manufacturing incumbent companies potentially can ensure their longevity and future-proof themselves by infusing ambidexterity throughout their organizations. Ambidextrous companies are equipped to achieve success in both current and future business environments, providing valued solutions to customers today and in the future. While these companies often excel at making incremental improvements to existing products, business, and operational models, they lack the skill set necessary for exploring new ways of creating value for customers, and commonly fail to bring promising breakthrough innovations from proven concept to revenue generation. To address these challenges, this thesis proposes a methodology consisting of four foundational principles for strengthening the innovation capacity of large manufacturing incumbents. The term "innovation engineering" is introduced and described to distinctly differentiate exploration-oriented work from exploitation-oriented work and demystify the exploration process and skills. The thesis also presents the concept of "intentional PSS design" as an approach to incorporate future aspirations and current capabilities into an evolutionary design process, connecting current limitations with future anticipated possibilities.The thesis proposes tools for leaders and coaches to support innovation engineering teams in their exploration journeys and bridge the gap between exploration and exploitation. The overall aim of the research is to future-proof large manufacturing incumbents by providing understanding about common challenges and possibilities, a framework for strengthened innovation capacity, incorporating the innovation engineering skills as core competencies, and the innovation engineering process as equally important to and diametrically different from the exploitation process.The research aims to increase awareness and knowledge about innovation engineering and enable infused ambidexterity so that large manufacturing incumbents can find their ways to adapt to a changing environment and reinvention of their ways to meet customer needs. The thesis also proposes ways to bridge between exploration and exploitation to enable a company-wide transition from a product-selling to problem-solving enterprise. By doing so, large manufacturing companies might prolong their lifespan and contribute solving
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| 20. |
- Elsakka, Amr, et al.
(författare)
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A mm-Wave Phased-Array Fed Torus Reflector Antenna with ±30° Scan Range for Massive-MIMO Base-Station Applications
- 2022
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Ingår i: IEEE Transactions on Antennas and Propagation. - 0018-926X .- 1558-2221. ; 70:5, s. 3398-3410
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Tidskriftsartikel (refereegranskat)abstract
- A phased-array fed reflector antenna system is presented which can be used for mm-wave base station applications. The proposed system is designed to support massive-Multi-Input-Multi-Output (MIMO) scenarios within a wide coverage (±30°) in the azimuth plane and a limited coverage at the elevation plane. A design and characterization methodology has been established to optimize the system for the operation in various line-of-sight conditions by adopting the maximum-ratio-transmission (MRT) and zero-forcing (ZF) MIMO algorithms. A two-user MIMO case study has been considered for the evaluation of the key system performance metrics, i.e. the effective isotropic radiated power, power consumption, signal-to-noise-ratio (SNR), and signal-to-interference-plus-noise-ratio (SINR). This study demonstrates that the phased-array fed reflector concept has a major advantage over traditional direct-radiating phased array (DRPA) antennas to reduce energy consumption. In the present example, it requires 12–14 dB less transmitted power as compared to the MRT-beamformed DRPAs for the same SNR, and 26–27 dB less transmitted power relatively to ZF-beamformed DRPA systems for the same SINR. A prototype, employing a 55 cm diameter torus reflector and operating at 28 GHz-band, has been manufactured and tested. The measurement results agree well with simulations.
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| 21. |
- Eriksson, Martin, 1970, et al.
(författare)
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Long-term effects of the antibacterial agent triclosan on marine periphyton communities
- 2015
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 34:9, s. 2067-2077
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Tidskriftsartikel (refereegranskat)abstract
- Triclosan is a widely used antibacterial agent that has become a ubiquitous contaminant in freshwater, estuary, and marine environments. Concerns about potential adverse effects of triclosan have been described in several recent risk assessments. Its effects on freshwater microbial communities have been well studied, but studies addressing effects on marine microbial communities are scarce. In the present study, the authors describe short- and long-term effects of triclosan on marine periphyton (microbial biofilm) communities. Short-term effects on photosynthesis were estimated after 60min to 210min of exposure. Long-term effects on photosynthesis, chlorophyll a fluorescence, pigment content, community tolerance, and bacterial carbon utilization were studied after exposing periphyton for 17d in flow-through microcosms to 0.316nM to 10000nM triclosan. Results from the short-term studies show that triclosan is toxic to periphyton photosynthesis. Half maximal effective concentration (EC50) values of 1080nM and 3000nM were estimated using (CO2)-C-14-incorporation and pulse amplitude modulation (PAM) fluorescence measurements, respectively. After long-term triclosan exposure in flow-through microcosms, photosynthesis estimated using PAM fluorometry was not inhibited by triclosan concentrations up to 1000nM but instead increased with increasing triclosan concentration. Similarly, at exposure concentrations of 31.6nM and higher, triclosan caused an increase in photosynthetic pigments. At 316nM triclosan, the pigment amounts were increased by a factor of 1.4 to 1.9 compared with the control level. Pollution-induced community tolerance was observed for algae and cyanobacteria at 100nM triclosan and higher. Despite the widespread use of triclosan as an antibacterial agent, the compound did not have any effects on bacterial carbon utilization after long-term exposure.
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| 22. |
- Folkow, Peter, 1968, et al.
(författare)
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Dynamic equations for fluid-loaded porous plates using approximate boundary conditions
- 2009
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 1520-8524 .- 0001-4966. ; 125:5, s. 2954-66
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Tidskriftsartikel (refereegranskat)abstract
- Systematically derived equations for fluid-loaded thin poroelastic layers are presented for time-harmonic conditions. The layer is modeled according to Biot theory for both open and closed pores. Series expansion techniques in the thickness variable are used, resulting in separate symmetric and antisymmetric plate equations. These equations, which are believed to be asymptotically correct, are expressed in terms of approximate boundary conditions and can be truncated to arbitrary order. Analytical and numerical results are presented and compared to the exact three dimensional theory and a flexural plate theory. Numerical comparisons are made for two material configurations and two thicknesses. The results show that the presented theory predicts the plate behavior accurately.
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| 23. |
- Gakidou, E., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
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Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1345-1422
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 24. |
- Harbst, Katja, et al.
(författare)
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Molecular profiling reveals low- and high-grade forms of primary melanoma.
- 2012
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036
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Tidskriftsartikel (refereegranskat)abstract
- For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
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| 25. |
- Holm, Anna, 1973-, et al.
(författare)
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Long term risk and costs of bleeding in men and women treated with triple antithrombotic therapy : An observational study
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Bleeding is the most common non-ischemic complication in patients with coronary revascularisation procedures, associated with prolonged hospitalisation and increased mortality. Many factors predispose for bleeds in these patients, among those sex. Anyhow, few studies have characterised the population receiving triple antithrombotic therapy (TAT) as well as long term bleeds from a sex perspective. We investigated the one year rate of bleeds in patients receiving TAT, potential sex disparities and premature discontinuation of TAT. We also assessed health care costs in bleeders vs non-bleeders. Setting Three hospitals in the County of ostergotland, Sweden during 2009-2015. Participants All patients discharged with TAT registered in the SWEDEHEART registry. Primary and secondary outcome measures All bleeds receiving medical attention during one-year follow-up were collected by retrieving relevant information about each patient from medical records. Resource use associated with bleeds was assigned unit cost to estimate the health care costs associated with bleeding episodes. Results Among 272 patients, 156 bleeds occurred post-discharge, of which 28.8% were gastrointestinal. In total 54.4% had at least one bleed during or after the index event and 40.1% bled post discharge of whom 28.7% experienced a TIMI major or minor bleeding. Women discontinued TAT prematurely more often than men (52.9 vs 36.1%, p = 0.01) and bled more (48.6 vs. 37.1%, p = 0.09). One-year mean health care costs were EUR 575 and EUR 5787 in non-bleeding and bleeding patients, respectively. Conclusion The high bleeding incidence in patients with TAT, especially in women, is a cause of concern. There is a need for an adequately sized randomised, controlled trial to determine a safe but still effective treatment for these patients.
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| 26. |
- Johansson, Christian, 1973-, et al.
(författare)
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Mechanism of lysozyme uptake in poly(acrylic acid) microgels
- 2009
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society. - 1520-6106 .- 1520-5207. ; 113:18, s. 6183-6193
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Tidskriftsartikel (refereegranskat)abstract
- The uptake of lysozyme by oppositely charged poly(acrylic acid) microgels was investigated by micromanipulator-assisted light microscopy and confocal microscopy. Lysozyme was observed to distribute nonuniformly within the microgels, forming a core-shell structure with considerably higher lysozyme concentration in the shell than in the core. The core-shell formation can be divided into two periods. During the first of these, the shell is formed during rapid microgel deswelling, and with no lysozyme diffusing into the microgel core. This is followed by a second period, during which microgel deswelling is negligible and lysozyme diffuses into the microgel core. Thus, the shell which is initially formed as a result of fast lysozyme transport to the gel network and fast protein-microgel interactions is able to carry a mechanical load and prevents deswelling during the latter core diffusion period. These two distinct regimes of lysozyme loading were also successfully described theoretically, demonstrating the importance of lysozyme cluster formation for the observed phenomena.
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| 27. |
- Johansson, Johan, et al.
(författare)
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Maintenance management in process industries:mapping current practices
- 2010
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Ingår i: Proceedings of the 17th EurOMA conference, 2010.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The overall purpose of this research is to map the maintenance management in three companies in the process industry sector and to analyse whether these companies apply a holistic perspective on their maintenance management. We have mapped our cases using the framework developed by Crespo Márquez et al. (2009) and our results show that even though maintenance is of utmost importance in the process industry, few companies have a strategic and holistic perspective on maintenance management.
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| 28. |
- Johansson, Martin, 1973, et al.
(författare)
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Approximate boundary conditions for a fluid-loaded elastic plate
- 2005
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 1520-8524 .- 0001-4966. ; 118:6, s. 3436-3446
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Tidskriftsartikel (refereegranskat)abstract
- Approximate boundary conditions for an infinite elastic layer immersed in a fluid are derived. By using series expansions in the thickness coordinate of the plate fields, the displacements fields are eliminated, adopting the three-dimensional equations of motion. The sums and differences of the boundary pressure fields and their normal derivatives are related through a set of approximate boundary conditions, one symmetric and one antisymmetric. These equations involve powers in the layer thickness together with partial derivatives with respect to time as well as the spatial variables in the plate plane. The approximate boundary conditions can be truncated to an arbitrary order, and explicit relations are presented including terms of order five. Comparisons are made with effective boundary conditions using classical plate theories. The numerical examples involve reflection and transmission of plane waves incident on the plate at different angles, as well as the pressure fields due to a line force. Three fluid-loading cases are studied: modest, heavy, and light loadings. The results using truncated approximate boundary conditions are compared to exact and classical plate solutions. The examples show that the accuracies of the power series approximations of order three and higher are very good in the frequency interval considered.
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| 29. |
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| 30. |
- Johansson, Martin, 1973, et al.
(författare)
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Dispersion free wave splittings for structural elements
- 2006
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Ingår i: Computers and Structures. - : Elsevier BV. - 0045-7949. ; 84:7, s. 514-27
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Tidskriftsartikel (refereegranskat)abstract
- Wave splittings are derived for three types of structural elements: membranes, Timoshenko beams, and Mindlin plates. The Timoshenko beam equation and the Mindlin plate equation are inherently dispersive, as is each Fourier component of the membrane equation in an angular decomposition of the field. The distinctive feature of the wave splittings derived in the present paper is that, in homogeneous regions, they transform the dispersive wave equations into simple one-way wave equations without dispersion. Such splittings have uses both for radial scattering problems in the 2D cases and for scattering problems in dispersive media. As an example of how the splittings may be applied, a direct scattering problem is solved for a membrane with radially varying density. The imbedding method is utilized, and agreement is obtained with an FE simulation.
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| 31. |
- Johansson, Martin, 1973
(författare)
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Wave Splitting and Effective Boundary Conditions for Structural Elements
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The subject of this thesis is twofold. The first part concerns the wave splitting of structural elements. The second part concerns approximate boundary conditions for fluid-loaded thin plates. Wave splitting is a mathematical tool for the formulation of scattering problems in the time domain that aims at solving inverse problems, e.g. material characterization and nondestructive testing. For the application of wave splitting and related techniques to mathematical models for structural elements, there are two situations where the usual approach is inadequate. These are when the original partial differential equation contains spatially dependent coefficients and when it is of higher order. The first situation arises, for instance, in problems formulated in cylindrical coordinates. A wave splitting for this situation is presented, which also admits the reduction to dispersion free dynamics for the split variables. A direct problem is solved and numerical results are presented and compared to an FEM solution. The second situation arises in the modelling of beams and plates. The usual approach involve the decoupling of waves propagating in the same direction, which introduces an exponentially growing behaviour in the split variables. An alternative method is presented, which comprises only the directional decoupling and thereby resolves this problem. A numerical example is given, in which a wave field is propagated along a Timoshenko beam further than would be possible for the standard methods. Approximate boundary conditions are derived for thin fluid-loaded elastic and porous plates. These are obtained by approximating the displacements in the plate by means of truncated series expansions in the thickness coordinate. The boundary conditions and the governing equations for the plate are used to eliminate all plate variables. This results in two partial differential equations relating the fluid pressures and normal displacement components on the two sides of the plate. Applications to several fluid, elastic and porous material combinations are presented numerically and compared to exact theory and classic plate theories.
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| 32. |
- Kimbung, Siker, et al.
(författare)
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Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer
- 2016
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 22:1, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Results: Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by down-regulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. (C)2015 AACR.
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| 33. |
- Konstantinou, Dimitrios, et al.
(författare)
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5G RAN architecture based on analog radio-over-fiber fronthaul over UDWDM-PON and phased array fed reflector antennas
- 2020
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Ingår i: Optics Communications. - : Elsevier BV. - 0030-4018. ; 454
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Tidskriftsartikel (refereegranskat)abstract
- This manuscript introduces a 5G radio access network architecture concept based on ultra-dense wavelength division multiplexing (UDWDM) and incorporating an optical fronthaul network that uses a novel wireless antenna system for radio frequency transmission and reception. A ring topology is proposed where optical signals travel within the 5G UDWDM passive optical networks and millimeter waves are generated in the optical line terminals by optical heterodyning. The wireless transmission of the millimeter waves is conducted by an innovative phased array fed reflector antenna approach for mobile communications that grants high antenna gain due to highly focused radiation characteristics, as well as multiplexing gain by multiple beam generation. Furthermore, beam steering is provided by a radio frequency analog beamformer network. Finally, implementation options synthesizing the total system are discussed.
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| 34. |
- Lewczuk, Piotr, et al.
(författare)
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.
- 2018
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Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 19:4, s. 244-328
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Tidskriftsartikel (refereegranskat)abstract
- In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
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| 35. |
- Marinovic, Tomislav, et al.
(författare)
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Effect of antenna array element separation on capacity of MIMO systems including mutual coupling
- 2019
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Ingår i: 2019 IEEE International Symposium on Antennas and Propagation and USNC-URSI Radio Science Meeting, APSURSI 2019 - Proceedings. ; , s. 415-416
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Konferensbidrag (refereegranskat)abstract
- In this paper, we study the effect of element separation in a base station array (BSA) on the downlink line-of-sight achievable sum-rate of MIMO systems in the presence of mutual coupling at the BSA. The channel matrix H is modeled using the embedded field patterns of the BSA and is used to analyze the outage performance for two single-element user equipments assuming no inter-user coupling.
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| 36. |
- Moncrieff, Marc D, et al.
(författare)
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Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease.
- 2022
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 40:34, s. 3940-3951
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Tidskriftsartikel (refereegranskat)abstract
- Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy.Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers. All were adult patients with pathologic stage pT1b/pT2a primary cutaneous melanomas who underwent SN biopsy between 2005 and 2020. Patient data, primary tumor and SN characteristics, and survival outcomes were analyzed.Three thousand six hundred seven patients were included. The median follow-up was 34 months. Pairwise disease comparison demonstrated no significant survival difference between N1a and N2a subgroups. Survival analysis identified a SN tumor deposit maximum dimension of 0.3 mm as the optimal cut point for stratifying survival. Five-year disease-specific survival rates were 80.3% and 94.1% for patients with SN metastatic tumor deposits ≥ 0.3 mm and < 0.3 mm, respectively (hazard ratio, 1.26 [1.11 to 1.44]; P < .0001). Similar findings were seen for overall disease-free and distant metastasis-free survival. There were no survival differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients. The newly identified high-risk (≥ 0.3 mm) subgroup comprised 271 (66.4%) of the AJCC IIIA cohort, whereas only 142 (34.8%) patients had SN tumor deposits > 1 mm in maximum dimension.Patients with AJCC IIIA melanoma with SN tumor deposits ≥ 0.3 mm in maximum dimension are at higher risk of disease progression and may benefit from adjuvant systemic therapy or enrollment into a clinical trial. Patients with SN deposits < 0.3 mm in maximum dimension can be managed similar to their SN-negative, AJCC IB counterparts, thereby avoiding regular radiological surveillance and more intensive follow-up.
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| 37. |
- Mäkeler, Hendrik, 1979-, et al.
(författare)
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Harald Nilsson hedersdoktor i Uppsala
- 2010
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Ingår i: Nordisk Numismatisk Unions Medlemsblad. - Köpenhamn : Nordisk Numismatisk Union. ; :1, s. 33-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 38. |
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| 39. |
- Pannee, Josef, 1979, et al.
(författare)
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The amyloid-beta degradation pattern in plasma A possible tool for clinical trials in Alzheimer's disease
- 2014
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 573, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid beta (A beta) is the main component of plaques, the central neuropathological hallmark in Alzheimer's disease (AD). A beta is derived from the amyloid precursor protein (APP) by beta- and gamma-secretase-mediated cleavages. A large number of A beta peptides are found in cerebrospinal fluid and these peptides are produced in specific metabolic pathways, which are important for diagnosis, in drug development and to explore disease pathogenesis. To investigate whether a similar pattern could be found also in blood samples, an immunoprecipitation (IP) based method for enrichment of A beta peptides from human plasma was developed. The peptides were analyzed using matrix-assisted-laser-desorption/ionization time-of-flight/time-of-flight mass spectrometry for A beta profiling and selected reaction monitoring (SRM) for MS quantification of A beta 1-38, A beta 1-40 and A beta 1-42 using tripe quadrupole MS. Sixteen N- or C-terminally truncated A beta peptides were reproducibly detected in human plasma, of which 11 were verified by tandem MS. In a pilot study including 9 AD patients and 10 controls, where A beta 1-38, A beta 1-40 and A beta 1-42 were quantified using SRM, no AD-associated change in plasma levels of the peptides were observed. Using MS-based measurement techniques, we show that several A beta peptides can be monitored in a single analysis and the developed methods have the potential to be used as a read out in clinical trials of drugs affecting APP processing or A beta homeostasis.
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| 40. |
- Petersson, Malin, et al.
(författare)
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Patient-reported symptom severity in a nationwide myasthenia gravis cohort : cross-sectional analysis of the Swedish GEMG study
- 2021
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 97:14, s. e1382-e1391
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: To describe myasthenia gravis activities of daily living (MG-ADL) in relation to clinical characteristics in a large Swedish nationwide cohort.Methods: In a cross-sectional prevalence cohort study, the Genes and Environment in Myasthenia Gravis study, performed from November 2018 through August 2019, patients with myasthenia gravis (MG) were invited to submit an extensive 106-item life environment questionnaire, including the MG-ADL score. Patients were classified into early-onset MG (EOMG, <50 years), late-onset MG (LOMG, >= 50 years), or thymoma-associated MG (TAMG). Comparisons of disease-specific characteristics were made between subgroups, sexes, and different MG-ADL scores.Results: A total of 1,077 patients were included, yielding a 74% response rate: 505 (47%) were classified as EOMG, 520 (48%) LOMG, and 45 (4%) TAMG. Mean age at inclusion was 64.3 years (SD 15.7) and mean disease duration was 14.6 years (SD 14.0). Complete MG-ADL scores (n = 1,035) ranged from 0p to 18p, where 26% reported a score of 0p. Higher MG-ADL scores were associated with female sex, obesity, and diagnostic delay (odds ratio [OR] 1.62, 1.72, and 1.69; p(adj) = 0.017, 0.013, and 0.008) and inversely correlated with high educational attainment (OR 0.59; p(adj) = 0.02), but not with age at inclusion, disease subtype, or disease duration. Almost half of the population (47%) reported MG-ADL >= 3p, corresponding to an unsatisfactory symptom state.Discussion: In this nationwide study, comprising more than 40% of the prevalent MG population in Sweden, almost half of the patients reported current disease symptoms associated with an unsatisfactory symptom state, indicating the need for improved treatment options.
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| 41. |
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| 42. |
- Ríos Bayona, Francisco, et al.
(författare)
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Comparison between shear strength based on Barton’s roughness profiles and equivalent synthetic profiles based on fractal theory
- 2018
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Ingår i: 52nd U.S. Rock Mechanics/Geomechanics Symposium. - : American Rock Mechanics Association (ARMA).
-
Konferensbidrag (refereegranskat)abstract
- A comprehensive understanding of the shear strength and the mechanical behavior of rock joints is to some extent still missing today. Several attempts have been made to develop empirical and analytical shear strength criteria that explain this mechanism. One of the most important parameters governing the shear strength of rock fractures is the surface roughness, which is generally determined using the Joint Roughness Coefficient (JRC). This parameter is often determined subjectively in the field by comparison with 10 predefined roughness profiles. Recent studies indicate that surface roughness can be accurately represented by using fractal analysis. The aim of this study is to perform a first attempt to investigate the mechanical equivalence in terms of the peak shear strength between synthetic rock fractures, where the surface roughness has been generated using fractal theory, and standard roughness profiles from Barton and Choubey, 1977, using the particle flow code PFC2D. The results from the numerical shear tests under constant normal load (CNL) are compared with the predicted peak shear strength using Barton’s criterion and a back-calculation of the JRC value is carried out.
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| 43. |
- Sjöström, Mats, et al.
(författare)
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Mandibular resection in patients with head and neck cancer : acute and long-term complications after reconstruction
- 2022
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Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis Group. - 0001-6489 .- 1651-2251. ; 142:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Background: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient.Aims/Objectives: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions.Material and Methods: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24).Results: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien–Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication.Conclusions: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien–Dindo grade IIIa–V events was significantly lower for patients treated with primary closure without grafts. Significance: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.
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| 44. |
- Sjöström, Mats, et al.
(författare)
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Mandibular resection in patients with head and neck cancer : acute and long-term complications after reconstruction
- 2022
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Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis Group. - 0001-6489 .- 1651-2251. ; 142:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Background The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient.Aims/Objectives This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions.Material and Methods We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24).Results Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien-Dindo >= IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication.Conclusions A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien-Dindo grade IIIa-V events was significantly lower for patients treated with primary closure without grafts Significance The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.
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| 45. |
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| 46. |
- Svenningsson, Anders, et al.
(författare)
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Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial
- 2022
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Ingår i: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 21:8, s. 693-703
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Tidskriftsartikel (refereegranskat)abstract
- Background B-cell depleting therapies are highly efficacious in relapsing-remitting multiple sclerosis but one such therapy, rituximab, is not approved for multiple sclerosis and no phase 3 trial data are available. We therefore examined the safety and efficacy of rituximab compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis to obtain data that might allow inclusion of rituximab in treatment guidelines. Methods RIFUND-MS was a multicentre, rater-blinded, active-comparator, phase 3, randomised controlled trial done at 17 Swedish university and community hospitals. Key inclusion criteria for participants were: age 18-50 years; relapsing-remitting multiple sclerosis or clinically isolated syndrome according to prevailing McDonald criteria; 10 years or less since diagnosis; untreated or only exposed to interferons or glatiramer acetate; and with clinical or neuroradiological disease activity in the past year. Patients were automatically randomly assigned (1:1) by the treating physician using a randomisation module in the Swedish multiple sclerosis registry, without stratification, to oral dimethyl fumarate 240 mg twice daily or to intravenous rituximab 1000 mg followed by 500 mg every 6 months. Relapse evaluation, Expanded Disability Status Scale rating, and assessment of MRI scans were done by examining physicians and radiologists masked to treatment allocation. The primary outcome was the proportion of patients with at least one relapse (defined as subacute onset of new or worsening neurological symptoms compatible with multiple sclerosis with a duration of more than 24 h and preceded by at least 30 days of clinical stability), assessed in an intention-to-treat analysis using log-binomial regression with robust standard errors. This trial is registered at ClinicalTrials.gov, NCT02746744. Findings Between July 1, 2016, and Dec 18, 2018, 322 patients were screened for eligibility, 200 of whom were randomly assigned to a treatment group (100 assigned to rituximab and 100 assigned to dimethyl fumarate). The last patient completed 24-month follow-up on April 21, 2021. 98 patients in the rituximab group and 97 patients in the dimethyl fumarate group were eligible for the primary outcome analysis. Three (3%) patients in the rituximab group and 16 (16%) patients in the dimethyl fumarate group had a protocol-defined relapse during the trial, corresponding to a risk ratio of 0.19 (95% CI 0.06-0.62; p=0.0060). Infusion reactions (105 events [40.9 per 100 patient-years]) in the rituximab group and gastrointestinal reactions (65 events [47.4 per 100 patient-years]) and flush (65 events [47.4 per 100 patient-years]) in the dimethyl fumarate group were the most prevalent adverse events. There were no safety concerns. Interpretation RIFUND-MS provides evidence that rituximab given as 1000 mg followed by 500 mg every 6 months is superior to dimethyl fumarate in preventing relapses over 24 months in patients with early relapsing-remitting multiple sclerosis. Health economic and long-term safety studies of rituximab in patients with multiple sclerosis are needed.
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| 47. |
- Tedeholm, Helen, 1978, et al.
(författare)
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Effectiveness of first generation disease-modifying therapy to prevent conversion to secondary progressive multiple sclerosis.
- 2022
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) has been associated with reduced relapse rates and accumulation of disability. However, studies examining impact of DMT on risk of transition to secondary progressive MS (SPMS) leveraging population-based nationwide data are still rare. Here, we determine the population incidence of conversion to SPMS using two consecutive nation-wide cohorts, one immediately before and one after the introduction of DMT in Sweden.METHODS: We included two consecutive population cohorts of relapsing-remitting MS (RRMS) from the Swedish national MS register for the periods 1975-1994 (n = 2161), before DMT availability, and 1995-2011 (n = 3510), in which DMTs, mainly first generation DMT (injectables), became available and eventually were used by 70% of patients. We explored the risk of transition to SPMS as a calendar year function encompassing the two cohorts. In addition, we determined the incidence of transition to SPMS through age strata below and above 50 years in untreated and treated patient subgroups.RESULTS: The risk of conversion to SPMS (adjusted for current age, current time since onset, calendar year and sex) was significantly lower in the second compared with the first population cohort (hazard ratio 0.58; CI 0.48, 0.70). The risk of SPMS conversion per calendar year decreased by 2.6% annually (p < 0.001) after 1995. The risk of SPMS conversion increased with age until age 50. Thereafter, it was unchanged or decreased among those with early MS onset age (<35 years), but continued to increase with onset at higher age, with similar trends in treated and untreated subgroups.CONCLUSION: The incidence of SPMS conversion significantly decreased at the population level after introduction of first generation DMTs by 1995. DMT efficiency was confirmed by a downward turn of the annual trajectory of the risk of SPMS conversion after 1995. An onset age determined pattern of variable SPMS incidence in higher age appeared in both treated and untreated strata. While first generation DMT delayed conversion to SPMS, their long-term effect was only moderate.
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- Öfverman, Charlotte, 1970-, et al.
(författare)
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The progesterone metabolite isoallopregnanolone is a subunit-selective antagonist of the GABA-A receptor
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Allopregnanolone is a progesterone metabolite that can negatively affect learning and induce anaesthesia in rats. It also impairs episodic memory in women. Allopregnanolone levels are elevated during the luteal phase of the menstrual cycle, during pregnancy, and during stress. Allopregnanolone is a strong positive modulator of the GABAA receptor. The subunit composition of the GABAA receptor is of importance for effects of modulators, and GABAA receptors including the α5-subunit are of significance for learning, while receptors with other subunits are involved in e.g. anesthesia. Isoallopregnanolone, a natural 3β-epimer of allopregnanolone, has been shown to antagonize allopregnanolone-induced anesthesia in rats. We tried to block the allopregnanolone-induced impairment of learning in rats in the Morris water maze test, using isoallopregnanolone (4–32 mg/kg). We also determined steroid concentrations in blood and brain tissue, and with whole-cell patch clamp we studied the effects of isoallopregnanolone and tetrahydrodeoxycorticosterone (a neurosteroid similar to allopregnanolone) on HEK-293 cells expressing the human α5β2γ2L GABAA receptor. Isoallopregnanolone did not block the negative effects of allopregnanolone (2 mg/kg) in the Morris water maze test. Our presumed antagonist actually had an agonistic effect on the tetrahydrodeoxycorticosterone-mediated potentiation of the GABA effect on the α5β2γ2L GABAA receptor. The baseline shift induced by tetrahydrodeoxycorticosterone alone was not reversed by isoallopregnanolone. A bidirectional epimerisation between allopregnanolone and isoallopregnanolone was also identified in the rat. The lack of antagonistic effect at the α5β2γ2L GABAA receptor together with the epimerisation of isoallopregnanolone to allopregnanolone would probably explain the lack of effect of our proposed antagonist on the allopregnanolone-induced impairment of learning
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