| 1. |
- Frykholm, Erik, 1985-
(author)
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The relevance and assessment of limb muscle function in individuals with chronic obstructive pulmonary disease
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Chronic obstructive pulmonary disease (COPD) is a disease that is characterised by persistent respiratory symptoms and airflow limitation. Consequences beyond the airways and lungs are common, and include limb muscle dysfunction. Limb muscle dysfunction is treated with exercise training, and should be preceded by assessments to individualise prescriptions. Guidelines recommend assessment of quadriceps strength, but limb muscle dysfunction affects more than strength. Other less investigated assessments may be of interest. During training, direct physiological (cardiorespiratory, metabolic, and biomechanical) and symptomatic responses are important, since they can affect training effectivity, and they may differ depending on whether arms or legs are used. The main aims of this thesis were to investigate the relevance of assessments of quadriceps function, feasibility and reliability of methods to assess quadriceps endurance, and to compare the direct physiological and symptomatic responses during arm and leg activities in people with COPD.Method: This thesis is based on four papers. These include one systematic review with a meta-analysis of studies comparing direct physiological and symptomatic responses to activities performed with the arms versus the legs, and three papers based on an international cross-sectional multicentre study investigating reliability, feasibility, and relevance of three leg extension assessments of quadriceps endurance. Relative and absolute reliability were determined via interclass correlation coefficient (ICC), coefficient of variation (CV %), and limits of agreement (LoA %) for measures of isokinetic total work, isokinetic fatigue index, isometric time to exhaustion, and isotonic repetitions to exhaustion. The relevance of the measures of quadriceps endurance and other quadriceps functions were determined by the association to functional capacity and physical activity with Pearson correlation analyses (r) and multiple linear regression models (R2, adjusted R2, Δ R2, and Δ adjusted R2).Results: Results from the meta-analyses show that leg-cycle ergometer resulted in greater tidal volume (137 mL), minute ventilation (4.8 L/min), and oxygen consumption (164 mL/min) compared to arm cycle ergometer, while symptomatic responses were similar. Physiological responses (e.g., minute ventilation and oxygen consumption) during arm compared to leg resistance training exercises were similar. Results from studies on functional activities depend on the type and intensity of the activity performed. Isokinetic total work was the measurement with the highest relative reliability (ICC = 0.98) and the smallest absolute reliability (e.g., CV% = 6.5). Isokinetic fatigue index, isometric, and isotonic measures demonstrated low-to-high relative reliability (ICC = 0.64, 0.88, 0.91), and absolute reliability was larger (e.g., CV% = 20.3, 14.9, and 15.8%). Participants performed better on the retest for isokinetic total work and isometric measurements (4.8 and 10%, p < 0.001). The feasibility was similar across protocols, with an average time consumption of< 7.5 minutes, limited perceived dyspnoea compared to leg fatigue, and no major adverse advents. The measures of quadriceps function had mostly similar (r = +/- 0.07–0.45) levels of correlations to the functional capacity and physical activity. In multiple regression analyses improved quadriceps power the models to predict functional capacity the most (Δ adjusted R2= 0.10, 0.15, adjusted R2 = 0.60, 0.39). Isotonic endurance was the only muscle function that improved all physical activity models (ΔR2 = 0.04–0.07, p < 0.05, R2 = 0.38–0.49).Conclusions: The results indicate that if the goal of an activity is to maximise physiological responses such as minute ventilation and oxygen consumption, activities involving the legs should be preferred. Symptomatic responses seems task and intensity dependent, which suggest that strategies used to reduce symptoms should be based on relative intensity. In the assessment of quadriceps endurance, isokinetic, isometric and isotonic protocols present low to very high relative reliability. Differences in reliability and the better performance at retest might reflect differences in ability to detect true change. Quadriceps power seems to be more relevant to functional capacity, and isotonic quadriceps endurance seems to be more relevant to physical activity.
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| 2. |
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| 3. |
- Alijan Farzad Lahiji, Faezeh
(author)
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Epitaxy of oxide and nitride thin films grown by magnetron sputtering
- 2023
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Licentiate thesis (other academic/artistic)abstract
- The need for electronic devices with new functionalities has caused research to move in a way to design and utilize materials with high-performance thermoelectricity, widely used in batteries, sensors, and electronic devices. Two-dimensional materials (2D) with unique structures and remarkable properties have been identified to fabricate oxide heteroepitaxy. The growth of heteroepitaxy has been focused on the growth of high-quality films on single crystalline substrates. The preferred orientation and the crystallization of the materials with thin or two-dimensional structures require an understanding of epitaxy. In epitaxial growth, using a specific, well- defined substrate with lattice constants close to that film is decisive in controlling the film orientation with high epitaxial quality. The electrical, optical, magnetic, and structural properties of the film are strongly determined by the texture and its epitaxial alignment. The majority of studies report epitaxial growth on Si and sapphire with different crystallographic orientations. The family of NaCl-structured materials covers a variety of nitrides and oxides broadly used in science and technology that have been epitaxially grown on monocrystalline Si and sapphire (Al2O3). In this thesis, the structure and optical properties of NiO are investigated as functions of oxygen content on Si(100) and c-Al2O3 using pulsed dc reactive magnetron sputtering. It is found that NiO with cubic structure is a single phase with predominant orientation along (111) on both substrates. It is fiber textured on Si(100), while twin domain epitaxy is achieved on c-Al2O3. The growth of two cases of metal oxide and nitride films (NiO and CrN) with rock-salt (NaCl) structure is also demonstrated on r-plane sapphire. It is revealed that the NaCl-structured materials NiO and CrN grow with a tilted orientation relative to the substrate. This characterization and analysis of the epitaxy, crystallography, and growth modes yield a single and identical epitaxial relationship of these two cubic materials on r-plane sapphire, in contrast to earlier studies on NaCl-structured materials on r-plane sapphire, indicating several different orientation relationships. The results advance the understanding of growth modes and unusual epitaxial relationships of two cases of metal oxide and nitride films with rock-salt (NaCl) structure broadly used in science and technology on r-plane sapphire.
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| 4. |
- Andersson, Jan, 1965-, et al.
(author)
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Regeringsuppdrag synfält : utredning om förutsättningar för undantag från de medicinska kraven för individer med synfältsbortfall
- 2022
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Reports (other academic/artistic)abstract
- I regeringsuppdraget (I2021/ 02412) framgår att VTI, i samarbete med Trafikverket och Transportstyrelsen, ska utreda förutsättningarna för undantagshantering från de medicinska föreskrifterna med avseende på synfältsbortfall (B-körkort). Vidare ska tre aspekter beaktas: hur andra länder gör, konsekvenser för den enskilde samt samhällsekonomiska konsekvenser. Slutrapporten påvisar att Sverige med gällande rättsligt ramverk inte kan genomföra de förslag som slutrapporten föreslår. Det innebär att det kommer att krävas juridiska förändringar. Givet att dessa förändringar genomförs och att ett nytt förfaringssätt nyttjas visar slutrapporten på att a) positiva effekter för den enskilde individen uppstår, b) samhällsekonomiska vinster uppstår och c) en rättssäker och rättvis prövning är möjlig. Slutrapporten redovisar dessutom hur ett urval av andra länder har hanterat handläggningen av individer med synfältsbortfall givet samma EU-direktiv som Sverige regleras av. Det framgår också av undersökningen att samtliga länder, som en förutsättning för undantag från de föreskrivna kraven avseende synfält, tillämpar krav eller rekommendationer om att ett praktiskt körprov ska utgöra del i underlaget för bedömning av körförmågan. Kunskapsläget med avseende på körförmågebedömningar för individer med synfältsbortfall redovisas och där framgår med tydlighet att perimetrin som Sverige utnyttjar som underlag för återkallelse av körkort inte kan predicera individers körförmåga. Perimetrin är dock viktig eftersom individer med synfältsbortfall som grupp kan vara olämpliga förare. Slutsatsen som forskningslitteraturen enstämmigt lyfter är att det behövs förarprov (på väg eller i en simulator) för att kunna genomföra en valid bedömning. Slutligen innehåller slutrapporten vilka problem (aktiviteter) som kvarstår för att skapa en lämplig och kvalitetssäkrad process. Dessutom presenteras den kronologiska ordning på aktiviteter som behöver genomföras. Kronologin krävs eftersom resultatet av lämplig metod och aktör påverkar det vidare arbetet med avseende på utformning av körprov och rättsligt ramverk. Slutrapportens slutsats är att Sverige har möjligheten att genomföra en förändring med avsevärda nyttor. Detta eftersom de valda aktörerna och de valda metoderna existerar idag och därför endast behöver utvecklas i viss mån för att säkerställa att individer med synfältsbortfall erbjuds en kvalitetssäkrad, rättssäker och rättvis process som dessutom bedöms vara samhällsekonomiskt lönsam.
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| 5. |
- Barucca, G., et al.
(author)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Journal article (peer-reviewed)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 6. |
- Bergthorsdottir, Ragnhildur, 1971, et al.
(author)
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Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency : a Swedish nationwide study
- 2024
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In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 295:3, s. 322-330
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Journal article (peer-reviewed)abstract
- Background: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown.Methods: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis.Results: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28).Conclusion: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.
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| 7. |
- Bostedt, Göran, et al.
(author)
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Adaptive pastoralists—Insights into local and regional patterns in livelihood adaptation choices among pastoralists in Kenya
- 2023
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In: Pastoralism. - : Springer Nature. - 2041-7136. ; 13:1
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Journal article (peer-reviewed)abstract
- Pastoralist adaptation strategies have to address multiple, overlapping, and often inter-related processes of socio-ecological change. The present study addresses the need for inter-regional comparative studies that account for different geographic, climate, and socio-economic contexts in order to understand how pastoralists adapt to changes in livelihood conditions. The paper uses data from a unique survey study of pastoralist households in four neighbouring counties in dryland Kenya. Taking our point of departure from an empirically based classification of the livelihood strategies available to pastoralists in the Horn of Africa, the survey offers novel insights into adaptation and fodder management strategies of pastoralist individuals and households. The results show that the use of migration as a strategy is more dependent on the ability to migrate than climate conditions. This is the case in localities where a substantial part of the land is subdivided, the population density is high, and where opportunities for migration are subsequently restricted. Diversification of livelihoods as a strategy is largely defined by opportunity. Intensification through active fodder management is mainly common in areas where there has been a proliferation of managed enclosures. Climate change will test the adaptive capacity of pastoralists in the studied region, and diversification and intensification strategies of both herd composition and livelihoods can be seen as strategies for increased climate resilience.
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| 8. |
- Brulin, E., et al.
(author)
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Healthcare in distress: A survey of mental health problems and the role of gender among nurses and physicians in Sweden
- 2023
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 339, s. 104-110
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Journal article (peer-reviewed)abstract
- Introduction:The present article aimed to investigate 1) if mental health problems (depression and burnout including the dimensions; emotional exhaustion, mental distance and cognitive and emotional impairment) differed between nurses and physicians in Sweden, 2) if any differences were explained by differences in sex compositions, and 3) if any sex differences were larger within either of the two professions. Method:Data were derived from a representative sample of nurses (n = 2903) and physicians (n = 2712) in 2022. Two scales were used to assess burnout (KEDS and BAT) and one to assess depression (SCL-6). The BAT scale has four sub-dimensions. Descriptive statistics and logistic regression were used to analyse each scale and dimension separately. Results:Results showed that 16-28 % of nurses and physicians reported moderate to severe symptoms of burnout. The prevalence differed between occupations across the scales and dimensions used. Nurses reported higher scores on KEDS while physicians reported higher scores on BAT including the four dimensions. Also, 7 % of nurses' and 6 % of physicians' scores were above the cut-off for major depression. The inclusion of sex in the models changed the odds ratios of differences between doctors and nurses in all mental health dimensions except mental distance and cognitive impairment. Limitations: This study was based on cross-sectional survey data which has some limitations. Conclusion:Our study suggests that the prevalence of mental health problems is prominent among nurses and physicians in Sweden. Sex plays an important role in the difference in the prevalence of mental health problems between the two professions.
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| 9. |
- Carlströmer Berthén, Nellie, et al.
(author)
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The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland
- 2023
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In: Microorganisms. - : MDPI. - 2076-2607. ; 11:5
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Journal article (peer-reviewed)abstract
- The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finlandby Nellie Carlströmer Berthén 1,2,*,† , Eszter Tompa 3,† , Susanne Olausson 1,2, Clara Nyberg 1, Dag Nyman 1,2, Malin Ringbom 1,4, Linda Perander 1,4, Joel Svärd 3, Per-Eric Lindgren 3,5, Pia Forsberg 3, Peter Wilhelmsson 3,5,‡, Johanna Sjöwall 3,6,‡ and Marika Nordberg 1,4,‡ 1Borrelia Research Group of the Aland Islands, 22100 Mariehamn, The Aland Islands, Finland2Bimelix AB, 22100 Mariehamn, The Aland Islands, Finland3Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linkoping University, 581 83 Linkoping, Sweden4The Aland Islands Healthcare Services, 22100 Mariehamn, The Aland Islands, Finland5Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden6Department of Infectious Diseases, Vrinnevi Hospital, 603 79 Norrkoping, Sweden*Author to whom correspondence should be addressed.†These authors contributed equally to the study.‡These authors contributed equally to the study.Microorganisms 2023, 11(5), 1100; https://doi.org/10.3390/microorganisms11051100Received: 30 March 2023 / Revised: 17 April 2023 / Accepted: 19 April 2023 / Published: 22 April 2023(This article belongs to the Special Issue Research on Ticks and Tick-Borne Pathogens)Download Browse Figures Versions NotesArticle Views585 AbstractThe AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.
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| 10. |
- Forward, Sonja, 1956-, et al.
(author)
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Barns skolresor – ett föräldraperspektiv
- 2023
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Reports (other academic/artistic)abstract
- Det övergripande syftet var att undersöka föräldrars vanor och inställning till transporter i samband med skolresor, årskurs 1–6. Studiens resultat baserades på en enkät och fokus i enkäten låg på det aktiva resandet men också resor med bil. Resultaten visade att majoriteten av barnen hade en resa på högst 2 km till skolan och det vanligaste färdsättet var gång eller cykel. Majoriteten av föräldrar som skjutsade sina barn med bil till skolan hade ett avstånd till skolan som översteg 5 km. Den sociala normen var starkt kopplat till föräldrarnas val av transporter Detta gällde framför allt de som lät barnet gå eller cykla till skolan men även de som skjutsade barnen. Resultaten visade också att föräldrar som skjutsade sina barn då avståndet var 5 eller 2 km till skolan skiljde sig från de som promenerade eller cyklade med avseende på attityden till resandet. Föräldrarna som skjutsade barnen till skolan hade en mera negativ attityd till att resa aktivt jämfört med de som redan reste på detta sätt. De instämde i högre grad än andra med att en resa med gång eller cykel skulle innebära omständliga förberedelser. De skjutsande föräldrarna tyckte också att det skulle vara svårare att låta barnen gå eller cykla. Däremot fanns det en medvetenhet om att barn som reser aktivt får en bättre hälsa samt att det hjälper dem att koncentrera sig i skolan. Detta var något som gällde oavsett hur de själva lät barnet resa till skolan. Resultaten visade även att det fanns en koppling mellan val av färdmedel och vana, vilka vanligtvis är svåra att ändra på. Trots detta svarade föräldrar som alltid skjutsade barnet till skolan att deras närstående skulle kunna få dem att ändra sina vanor. Oron för att barnen skulle utsättas för en försämrad luftkvalitet i skolans närhet, i samband med att föräldrar lämnade och hämtade barnen med bil, var inte särskilt utbredd. De flesta undvek att lämna motorn på tomgång, men en mindre andel av föräldrarna, ca 15 procent, lät bilen gå på tomgång i samband med lämning/hämtning. Lite under hälften av föräldrarna parkerade en bit bort, men detta verkade inte bero på en oro för exponering av luftföroreningar, snarare att det var svårt att finna en lämplig plats att stanna på. Flera konkreta förslag på förbättringar av infrastrukturen i skolans närhet delgavs i kommentarer i enkätens slut. Där lyftes även problematiken med miljön i skolans närområde, med stressade bilister och en farlig trafikmiljö, och man efterlyste olika lösningar för att göra denna miljö mer trygg och säker. För att möjliggöra att så många elever som möjligt ska kunna gå eller cykla till skolan, krävs en ökad medvetenhet om behovet av fysisk aktivitet och på vilket sätt barnen påverkas av luftföroreningar. Därutöver kan föräldrar behöva hjälp med att övervinna eventuella hinder. Det behövs även ökat fokus på säkrare och tryggare vägar till skolan. Resultaten visar en potential att påverka gruppen som alltid skjutsar barnen att låta dem ta sig på skolan på något annat sätt. Samtidigt kommer det att finnas kvar situationer då föräldrar behöver skjutsa barnen till skolan, varför utrymmena vid skolan eller i närheten bör vara utformade så att trängsel och mindre trafiksäkra situationer undviks.
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| 11. |
- Forward, Sonja, 1956-, et al.
(author)
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Motorcyklister – utbildning, erfarenhet, syn på risk och olycksinblandning
- 2022
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Reports (other academic/artistic)abstract
- Det övergripande syftet med denna studie var att bidra till att förbättra trafiksäkerheten för förare av tvåhjulig motorcykel. Ett annat syfte var att undersöka orsaken till varför olyckor inträffar och motorcyklisters syn på risker i trafiken. I studien ingick fyra delstudier: registerstudie, enkätstudie och två intervjustudier. Både registerstudien och enkätstudien jämfördes med en grupp som skadats i trafiken med en kontrollgrupp. Resultaten från registerstudien visade att cirka 80 procent av de skadade förarna hade en giltig behörighet. Jämfört med kontrollgruppen hade skadegruppen något fler underkända kunskapsprov. Enkätstudien visade att de vanligaste olyckorna var singelolyckor och att cirka en femtedel av de skadade var helt eller delvis vållande till olyckan. Enligt intervjustudien med drabbade motorcyklister som varit vållande till olyckan berodde det på bristande uppmärksamhet och att bilförarens beteende misstolkades. Resultatet från regressionsanalysen visade att 55 procent av de variabler som ingår i Theory of Planned Behaviour förklarade deras avsikt att överträda hastighetsbestämmelser vilket innebär att detta beteende kan kopplas till medvetna felhandlingar. En annan slutsats är att olycksinblandning inte alltid ökar deras riskmedvetenhet. Frågor baserade på T-Locus of Control visade att den troligaste orsaken till en olycka, enligt motorcyklisterna, är att andra fordonsförares brister i sin körning snarare än det egna beteendet. Detta gällde oavsett om man var vållande till olyckan eller inte vilket i sin tur minskar motivationen att förändra sitt eget beteende. Slutsatsen är att utbildning inte kan kopplas till olycksinblandning, däremot gick det att fastslå att hastighetsöverträdelser kan kopplas till medvetna felhandlingar. Det sistnämnda styrker behovet av en rad olika utbildningsinsatser. Samtidigt är det viktigt att betona att utbildningen måste hålla hög kvalitet och att den är elevcentrerad, det vill säga utgår ifrån elevens tidigare erfarenheter samtidigt som den utmanar redan etablerade föreställningar. Studien avslutas med en rad rekommendationer för att öka motorcyklisters trafiksäkerhet.
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| 12. |
- Framke, Elisabeth, et al.
(author)
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Contribution of income and job strain to the association between education and cardiovascular disease in 1.6 million Danish employees
- 2020
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 41:11, s. 1164-1178
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Journal article (peer-reviewed)abstract
- Aims: We examined the extent to which associations between education and cardiovascular disease (CVD) morbidity and mortality are attributable to income and work stress.Methods and results: We included all employed Danish residents aged 30–59 years in 2000. Cardiovascular disease morbidity analyses included 1 638 270 individuals, free of cardiometabolic disease (CVD or diabetes). Mortality analyses included 41 944 individuals with cardiometabolic disease. We assessed education and income annually from population registers and work stress, defined as job strain, with a job-exposure matrix. Outcomes were ascertained until 2014 from health registers and risk was estimated using Cox regression. During 10 957 399 (men) and 10 776 516 person-years (women), we identified 51 585 and 24 075 incident CVD cases, respectively. For men with low education, risk of CVD was 1.62 [95% confidence interval (CI) 1.58–1.66] before and 1.46 (95% CI 1.42–1.50) after adjustment for income and job strain (25% reduction). In women, estimates were 1.66 (95% CI 1.61–1.72) and 1.53 (95% CI 1.47–1.58) (21% reduction). Of individuals with cardiometabolic disease, 1736 men (362 234 person-years) and 341 women (179 402 person-years) died from CVD. Education predicted CVD mortality in both sexes. Estimates were reduced with 54% (men) and 33% (women) after adjustment for income and job strain.Conclusion: Low education predicted incident CVD in initially healthy individuals and CVD mortality in individuals with prevalent cardiometabolic disease. In men with cardiometabolic disease, income and job strain explained half of the higher CVD mortality in the low education group. In healthy men and in women regardless of cardiometabolic disease, these factors explained 21–33% of the higher CVD morbidity and mortality.
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| 14. |
- Handin, Niklas, et al.
(author)
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Conditions for maintenance of hepatocyte differentiation and function in 3D cultures
- 2021
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In: iScience. - : Cell Press. - 2589-0042. ; 24:11
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Journal article (peer-reviewed)abstract
- Spheroid cultures of primary human hepatocytes (PHH) are used in studies of hepatic drug metabolism and toxicity. The cultures are maintained under different cone-lions, with possible confounding results. We performed an in-depth analysis of the influence of various culture conditions to find the optimal conditions for the maintenance of an in vivo like phenotype. The formation, protein expression, and function of PHH spheroids were followed for three weeks in a high-throughput 384-well format. Medium composition affected spheroid histology, global proteome profile, drug metabolism and drug-induced toxicity. No epithelial-mesenchymel transition was observed. Media with fasting glucose and insulin levels gave spheroids with phenotypes closest to normal PHH. The most expensive medium resulted in PHH features most divergent from that of native PHH. Our results provide a protocol for culture of healthy PHH with maintained function a prerequisite for studies of hepatocyte homeostasis and more reproducible hepatocyte research.
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| 15. |
- Jarlert, Anders, et al.
(author)
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”Quislingkyrkan” i Danmark och Sverige
- 2020
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In: Stiftshistoria och prästhistoria : Kyrkohistoriska studier till minnet av Ragnar Norrman - Kyrkohistoriska studier till minnet av Ragnar Norrman. - 0491-6786. - 9789198249187 ; 78, s. 31-38
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Book chapter (peer-reviewed)
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| 16. |
- Karlsson, Bo, 1951-, et al.
(author)
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Neuropeptide Y and measures of stress in a longitudinal study of women with the fibromyalgia syndrome
- 2023
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In: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 23:1, s. 59-65
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Neuropeptide Y is associated with stress in animal and human laboratory studies. However, data from clinical studies are scarce and no clinical longitudinal studies have been published. The aim of this clinical study was to assess the possible association between changes in the levels of pain, depression, and stress measures, on the one hand, and plasma neuropeptide Y levels, on the other.METHODS: Forty-four women with the fibromyalgia syndrome were exposed to a Cognitive Behavioral Therapy intervention. Levels of the plasma neuropeptide Y as well as pain, depression, and stress measures were obtained at the start and at the end of the intervention, and after a further six month follow-up. Based on these data, a before-and-after analysis was performed.RESULTS: Almost all measures of pain, depression, and stress improved during the study; specifically, variables measuring life control (coping), depression, and stress-related time urgency improved significantly. Moreover, during the same time period, the mean plasma neuropeptide Y level was reduced from 93.2 ± 38.8 fmol/mL before the Cognitive Behavioral Therapy to 75.6 ± 42.9 fmol/mL (p<0.001) at the end of the study.CONCLUSIONS: After exposure to a Cognitive Behavioral Therapy intervention, levels of most of the pain, depression, and stress measures improved, half of them significantly, as did the levels of neuropeptide Y. This circumstance indicates a possible functional relationship between pain-depression-stress and neuropeptide Y.
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| 17. |
- Klässbo, Maria, et al.
(author)
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I exercise to postpone death : Interviews with persons with hip and/or knee osteoarthritis who are attending an osteoarthritis school
- 2022
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In: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 38:11, s. 1667-1682
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Journal article (peer-reviewed)abstract
- Background: Physical activity (PA) and exercise constitute the first line of treatment for osteoarthritis (OA) of the hip and/or knee. Even though the symptoms may vary, OA should be considered a chronic disease and therefore PA and exercise should be performed lifelong. That needs knowledge and motivation.Purpose: The purpose of this study was to explore and create a deeper understanding of the motivational processes for PA and exercise for persons with hip and/or knee OA who have participated in a self-management program OA school that included long-term exercise supervised by physical therapists.Methods: Twenty-two in-depth interviews were conducted with 18 participants recruited from the OA school at a Physical Therapy Rehabilitation Clinic in Sweden. The interviews were analyzed with qualitative content analysis.Results: The analysis resulted in one main theme, Developing health literacy to encourage motivational processes for PA and exercise in OA and four themes: 1) meeting an established self-management program; 2) carrying my life history; 3) understanding the intelligence of the body; and 4) growing in existential motivation.Conclusion: Motivation for being physically active and to exercise, the life history in relation to PA and what creates existential motivation are important areas to ask questions about when people come to OA schools. Knowledge about the signals of the body connected to OA should be implemented in OA schools in order to motivate people to live an active life despite OA. Health literacy and the awareness of how PA can postpone death are likely to be important for existential motivation.
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| 18. |
- Knutsson, Per, 1971, et al.
(author)
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Perspectives on enclosures in pastoralist drylands: From contradictory evidence to the formulation of innovative land management strategies
- 2021
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In: World Development Perspectives. - : Elsevier BV. - 2452-2929 .- 2468-0532. ; 23
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Journal article (peer-reviewed)abstract
- Drylands in Sub-Saharan Africa are subject to rapid and enduring population increase, agricultural expansion, land large-scale infrastructure developments, as well as climate change, affecting some 265 million pastoralists and agro-pastoralists. These changes are promoting a transition from traditional pastoralist ways of life characterized by seasonal mobility, towards more sedentary livelihoods based on more intensive and commercial uses of land-based resources. As part of of this ongoing transition, establishment of enclosures on pastoralist commons is emerging as a default, but highly contested, development pathway. Based on a review of the current enclosure debate across the natural, economic, and social sciences, with a geographical focus on the East African drylands, we discuss the potential and limitations of enclosures as land management tool, and propose a conceptual framework for how enclosures can act as an integral part of sustainable pastoralist land use. Such a framework constitute an important piece of the puzzle for more productively linking the urgent need of innovative ways of managing pastoralist rangelands, to the present international and national commitments to restoration of degraded lands.
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| 19. |
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| 20. |
- Lilja-Lund, Otto, et al.
(author)
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Wide temporal horns are associated with cognitive dysfunction, as well as impaired gait and incontinence
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- The association between morphology of the brain and symptoms of suspected idiopathic normal pressure hydrocephalus (iNPH) is largely unknown. We investigated how ventricular expansion (width of the temporal horns [TH], callosal angle [CA], and Evans' index [EI]) related to symptom severity in suspected iNPH. Participants (n=168; 74.9 years +/- SD 6.7; 55% females) from the general population underwent neurological examination, computed tomography, and neuropsychological testing. Multiple linear regression analysis revealed that wide TH was independently associated with all examined iNPH symptoms (p<0.01) except for fine-motor performance, whereas a narrow CA only was associated to specific motor and cognitive functions (p<0.05). TH and EI correlated significantly with incontinence (r(s) 0.17 and r(s) 0.16; p<0.05). In conclusion, wide TH was significantly associated with most iNPH-symptoms. This finding potentially reflects the complex nature of the hippocampus, however further studies are needed to demonstrate functional connectivity.
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| 21. |
- Marklund, Sarah, MSc, 1986-
(author)
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COPD management : exploring conditions for, and experiences of, evidence-based care and eHealth
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and premature death worldwide. It is a systemic disease that affects the whole person, although dyspnea is the mostprominent symptom. COPD is expected to increase in prevalence during the coming 40 years due to an increase in relevant risk behaviors, and today over 230 million people suffer from COPD worldwide. A common extra pulmonary manifestation of the disease is quadriceps dysfunction, where muscle strength, power, and/or endurance properties are reducedand affect everyday function. However, reference values and valid reference equations are needed to evaluate and offer appropriate treatment for quadriceps dysfunction. Moreover, a crucial part of COPD management is pulmonary rehabilitation, e.g., where disease management and strategies are conveyed and put into practice. However, due to knowledge gaps within health care, we need to develop new ways of informing and supporting people with COPD. One way is through eHealth, although these sources must be evaluated so that they constructively contribute to health care.Aim: The overall aim of this thesis is to explore the conditions for, and perspectives on, evidence-based care and eHealth in COPD management. This aim is twofold. The first is to explore the experiences, interactions, and context of using eHealth tools in managing COPD in primary carefrom the perspective of people with COPD and health care professionals (HCPs). The second is to develop reference values and equations for quadriceps function.Method: This dissertation contains three papers (Papers I, II, and III) based on individual interviews analyzed with qualitative research methods in which an eHealth tool, the COPD Web, is evaluated. Lastly, it contains one paper(Paper IV) based on an international multicenter data collection analyzed with quantitative research methods.Results: Paper I: The findings indicate that the level of motivation, comfortability with IT tools, and health literacy seem to affect the usage of an eHealth tool over time. Some level of use and the passage of time appears to be needed to perceive gained benefits from the eHealth tool. In short, this suggests that eHealth tools such as the COPD Web can be suitable for supporting COPD-specific self-management skills. Paper II: The findings indicated that using the COPD Web provided knowledge support for HCPs and improved the quality of care for people with COPD. However, it seems some barriers need to be addressed to successfully implement the eHealth tool in daily practice. Paper III: Findings lead to the theme “Perceiving enough control to enable action”, which suggests that having or perceiving a certain amount of control is essential to maintain or increase the level of physical activity when one has COPD and uses an eHealth tool. Paper IV: The findings indicate that for people without COPD, age, sex, height, and BMI explained 50 – 70 % of the variance of quadriceps strength, endurance, and power. Our findings also suggested moderate construct validity of the reference equations in people with COPD.Conclusion: To conclude, the web-based eHealth tool, the COPD Web, seems to support and help when self-managing COPD and treating people with COPD. There are still barriers for people with COPD to use a web-based eHealth tool, and we probably ought to screen people with COPD for health literacy before discussing and deciding on PR strategies with them. There are still barriers to implementing new tools in the health care setting, which should need time, support, and education to circumvent. Findings regarding the developed reference values and equations for quadriceps strength, power, and endurance will make further tailoring of the treatment regime for the individual possible. As such, this, too, should assist in improving disease management, although the construct validity of the equations was moderate.
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| 22. |
- Nyberg, Andre, Docent, 1984-, et al.
(author)
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Effects of low-load/high-repetition resistance training on exercise capacity, health status and limb muscle adaptation in patients with severe COPD : a randomized controlled trial
- 2021
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In: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 159:5, s. 1821-1832
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Journal article (peer-reviewed)abstract
- Background: Training volume is paramount in the magnitude of physiological adaptations following resistance training. However, patients with severe COPD are limited by dyspnea during traditional two-limb low-load/high-repetition resistance training (LLHR-RT), resulting in suboptimal training volumes. During a single exercise session, single-limb LLHR-RT decreases the ventilatory load and enables higher localized training volumes compared with two-limb LLHR-RT.Research Question: Does single-limb LLHR-RT lead to more profound effects compared with two-limb LLHR-RT on exercise capacity (6-min walk distance [6MWD]), health status, muscle function, and limb adaptations in patients with severe COPD?Study Design and Methods: Thirty-three patients (mean age 66 ± 7 years; FEV1 39 ± 10% predicted) were randomized to 8 weeks of single- or two-limb LLHR-RT. Exercise capacity (6MWD), health status, and muscle function were compared between groups. Quadriceps muscle biopsy specimens were collected to examine physiological responses.Results: Single-limb LLHR-RT did not further enhance 6MWD compared with two-limb LLHR-RT (difference, 14 [–12 to 39 m]. However, 73% in the single-limb group exceeded the known minimal clinically important difference of 30 m compared with 25% in the two-limb group (P = .02). Health status and muscle function improved to a similar extent in both groups. During training, single-limb LLHR-RT resulted in a clinically relevant reduction in dyspnea during training compared with two-limb LLHR-RT (–1.75; P = .01), but training volume was not significantly increased (23%; P = .179). Quadriceps muscle citrate synthase activity (19%; P = .03), hydroxyacyl-coenzyme A dehydrogenase protein levels (32%; P < .01), and capillary-to-fiber ratio (41%; P < .01) were increased compared with baseline after pooling muscle biopsy data from all participants.Interpretation: Single-limb LLHR-RT did not further increase mean 6MWD compared with two-limb LLHR-RT, but it reduced exertional dyspnea and enabled more people to reach clinically relevant improvements in 6MWD. Independent of execution strategy, LLHR-RT improved exercise capacity, health status, muscle endurance, and enabled several physiological muscle adaptations, reducing the negative consequences of limb muscle dysfunction in COPD.
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| 23. |
- Nyberg, Lillemor A., 1955-, et al.
(author)
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Long-term effects of group exercise intervention on maximal step-up height in middle-aged female primary care patients with obesity and other cardio-metabolic risk factors
- 2020
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In: BMC Sports Science, Medicine and Rehabilitation. - : BioMed Central (BMC). - 2052-1847. ; 12:1
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Journal article (peer-reviewed)abstract
- Background: Low physical performance is a predictor of morbidity and mortality. This study looks at long-term effects of an exercise intervention on maximal step-up height (MSH) in individuals with low physical function. Factors associated with changes in MSH was studied.Methods: Female patients (n = 101), mean (SD) age of 52 (11) years, were recruited for a 3-month group exercise intervention including 2-3 sessions/week of mixed aerobic fitness and strength training. MSH, weight, body mass index (BMI), waist circumference, maximal oxygen consumption (VO2-max), self-reported health (SF-36) and physical activity (PA) were measured at baseline (T0), after 3 months (T1) and after 14-30 (mean 22) months (T2). Relationships between changes in MSH (cm) and age, baseline MSH, time to follow-up, changes in anthropometric measurements, VO2-max, SF-36 and PA were studied with regression analyses.Results: MSH, significantly, increased from T0 to T1, 27.2 (5.7) to 29.0 (5.5) cm and decreased to 25.2 (5.5) cm at T2. Time to follow-up (B = - 0.42, p < 0.001) and change in BMI (B = - 0.29, p = 0.012) correlated significantly to changes in MSH. Waist circumference, VO2-max, PF and exercise/physical activity levels were significantly improved at T2, while BMI did not change. In a univariate logistic regression model, maintenance of MSH correlated to the extent of mixed training (OR 3.33, 95% CI 1.25-8.89). In a multivariate logistic regression model adjusted for important factors the correlation was not significant. However, MSH was significantly higher in individuals participating in 2-3 session per week compared to one session.Conclusions: A 3-month group exercise intervention increased MSH, improved fitness, decreased risk in female patients with elevated cardio-metabolic risk. After an average of 22 months MSH was reduced while positive effects remained for waist circumference, VO2-max, physical function and physical activity. However, regular group exercise 2-3 times per week with mixed aerobic fitness and strength training was associated with maintenance of MSH in a subgroup of patients. We suggest that such an intervention including regular support from healthcare professionals is a successful approach for maintaining improved leg-muscle strength among primary care patients.Trial registration: ISRCTN21220201 September 18, 2019, retrospectively registered.
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| 24. |
- Nyberg, Markus, et al.
(author)
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Modeling protein target search in human chromosomes
- 2021
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In: Physical Review Research. - : American Physical Society. - 2643-1564. ; 3:1
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Journal article (peer-reviewed)abstract
- Several processes in the cell, such as gene regulation, start when key proteins recognize and bind to short DNA sequences. However, as these sequences can be hundreds of million times shorter than the genome, they are hard to find by simple diffusion: diffusion-limited association rates may underestimate in vitro measurements up to several orders of magnitude. Moreover, the rates increase if the DNA is coiled rather than straight. Here we model how this works in vivo in mammalian cells. We use chromatin-chromatin contact data from Hi-C experiments to map the protein target-search onto a network problem. The nodes represent DNA segments and the weight of the links are proportional to measured contact probabilities. We then put forward a diffusion-reaction equation for the density of searching protein that allows us to calculate the association rates across the genome analytically. For segments where the rates are high, we find that they are enriched with active gene starts and have high RNA expression levels. This paper suggests that the DNA's 3D conformation is important for protein search times in vivo and offers a method to interpret protein-binding profiles in eukaryotes that cannot be explained by the DNA sequence itself.
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| 25. |
- Ronne-Engström, Elisabeth, et al.
(author)
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Trends in incidence and treatments of spontaneous subarachnoid hemorrhage : a 10 year hospital based study
- 2024
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In: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 166:1
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Journal article (peer-reviewed)abstract
- BackgroundImproved endovascular methods make it possible to treat complex ruptured aneurysms, but surgery is still needed in certain cases. We evaluated the effects on the clinical results of the changes in aneurysm treatment.MethodsThe study cohort was 837 patients with spontaneous subarachnoid hemorrhage (SAH) and one or multiple aneurysms, admitted to Dept of Neurosurgery, Uppsala University Hospital from 2012 to 2021. Demography, location and treatment of aneurysms, neurologic condition at admission and discharge, mortality and last tier treatment of high intracranial pressure (ICP) was evaluated. Functional outcome was measured using the Extended Glasgow Outcome Scale (GOSE) Data concerning national incidences of stroke diseases was collected from open Swedish databases.ResultsEndovascular methods were used in 666 cases (79.6%). In 111 (13.3%) with stents. Surgery was performed in 115 cases (13.7%) and 56 patients (6.7%) had no aneurysm treatment. The indications for surgery were a hematoma (51 cases, 44.3%), endovascular treatment not considered safe (47 cases, 40.9%), or had been attempted without success (13 cases, 11.3%). Treatment with stent devices increased, and with surgery decreased over time. There was a trend in decrease in hemicraniectomias over time. Both the patient group admitted awake (n = 681) and unconscious (n = 156) improved significantly in consciousness between admission and discharge. Favorable outcome (GOSE 5–8) was seen in 69% for patients admitted in Hunt & Hess I-II and 25% for Hunt & Hess III-V. Mortality at one year was 10.9% and 42.7% for those admitted awake and unconscious, respectively.The number of cases decreased during the study period, which was in line with Swedish national data.ConclusionsThe incidence of patients with SAH gradually decreased in our material, in line with national data. The treatment policy in our unit has been shifting to more use of endovascular methods. During the study period the use of hemicraniectomies decreased.
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| 26. |
- Sonderby, Ida E., et al.
(author)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
-
Journal article (peer-reviewed)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 27. |
- Stranne, Johan, 1970, et al.
(author)
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Single institution followed by national implementation of systematic surgical quality control and feedback for radical prostatectomy: a 20-year journey
- 2020
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In: World Journal of Urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 38, s. 1397-1411
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Journal article (peer-reviewed)abstract
- Purpose: The demand for objective and outcome-based facts about surgical results after radical prostatectomy (RP) is increasing. Systematic feedback is also essential for each surgeon to improve his/her performance. Methods: RP outcome data (e.g., pT-stage and margin status) have been registered at Sahlgrenska University Hospital (SUH) since 1988 and patient-related outcome measures (PROM) have been registered since 2001. The National Prostate Cancer Registry (NPCR) has covered all Regions in Sweden since 1998 and includes PROM-data from 2008. Initially PROM was on-paper questionnaires but due since 2018 all PROMs are collected electronically. In 2014 an on-line “dashboard” panel was introduced, showing the results for ten quality-control variables in real-time. Since 2017 all RP data on hospital, regional, and national levels are publicly accessible on-line on “www.npcr.se/RATTEN”. Results: The early PROM-data from SUH have been used for internal quality control. As national clinical and PROM-data from the NPCR have been made accessible on-line and in real-time we have incorporated this into our pre-existing protocol. Our data are now internally available as real-time NPCR reports on the individual surgeons’ results, as well as ePROM data. We can compare the results of each surgeon internally and to other departments’ aggregated data. The public can access data and compare hospital level data on “RATTEN”. Conclusions: The process of quality control of RP locally at SUH, and nationally through the NPCR, has been long but fruitful. The online design, with direct real-time feedback to the institutions that report the data, is essential.
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| 28. |
- Suur, Bianca E., et al.
(author)
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Therapeutic potential of the Proprotein Convertase Subtilisin/Kexin family in vascular disease
- 2022
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
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Journal article (peer-reviewed)abstract
- Proprotein convertase subtilisin/kexins (PCSKs) constitute a family of nine related proteases: PCSK1-7, MBTPS1, and PCSK9. Apart from PCSK9, little is known about PCSKs in cardiovascular disease. Here, we aimed to investigate the expression landscape and druggability potential of the entire PCSK family for CVD. We applied an integrative approach, combining genetic, transcriptomic and proteomic data from three vascular biobanks comprising carotid atherosclerosis, thoracic and abdominal aneurysms, with patient clinical parameters and immunohistochemistry of vascular biopsies. Apart from PCSK4, all PCSK family members lie in genetic regions containing variants associated with human cardiovascular traits. Transcriptomic analyses revealed that FURIN, PCSK5, MBTPS1 were downregulated, while PCSK6/7 were upregulated in plaques vs. control arteries. In abdominal aneurysms, FURIN, PCSK5, PCSK7, MBTPS1 were downregulated, while PCSK6 was enriched in diseased media. In thoracic aneurysms, only FURIN was significantly upregulated. Network analyses of the upstream and downstream pathways related to PCSKs were performed on the omics data from vascular biopsies, revealing mechanistic relationships between this protein family and disease. Cell type correlation analyses and immunohistochemistry showed that PCSK transcripts and protein levels parallel each other, except for PCSK9 where transcript was not detected, while protein was abundant in vascular biopsies. Correlations to clinical parameters revealed a positive association between FURIN plaque levels and serum LDL, while PCSK6 was negatively associated with Hb. PCSK5/6/7 were all positively associated with adverse cardiovascular events. Our results show that PCSK6 is abundant in plaques and abdominal aneurysms, while FURIN upregulation is characteristic for thoracic aneurysms. PCSK9 protein, but not the transcript, was present in vascular lesions, suggesting its accumulation from circulation. Integrating our results lead to the development of a novel 'molecular' 5D framework. Here, we conducted the first integrative study of the proprotein convertase family in this context. Our results using this translational pipeline, revealed primarily PCSK6, followed by PCSK5, PCSK7 and FURIN, as proprotein convertases with the highest novel therapeutic potential.
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| 29. |
- Sønderby, Ida E., et al.
(author)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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In: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
-
Journal article (peer-reviewed)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 30. |
- van der Meer, Dennis, et al.
(author)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Journal article (peer-reviewed)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 31. |
- Wirestam, Lina, et al.
(author)
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Plasma Osteopontin Reflects Tissue Damage in Acute Pancreatitis
- 2023
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In: Biomedicines. - : MDPI. - 2227-9059. ; 11:6
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Journal article (peer-reviewed)abstract
- Several scoring systems for clinical prediction of the severity of acute pancreatitis (AP) have been proposed. Yet, there is still a need for an easy-to-measure biomarker. Osteopontin (OPN) may be released to the circulation early during tissue injury, but the significance of OPN in AP has not yet been established. We aimed to evaluate plasma levels of OPN in relation to the severity of AP. In 39 individuals with confirmed AP, plasma was collected on the day of admission and consecutively for three days thereafter. Sex- and age-matched healthy blood donors (n = 39) served as controls. Plasma OPN was measured by a commercial enzyme-linked immunosorbent assay. At admission, patients with AP displayed higher OPN, 156.4 ng/mL (IQR 111.8-196.2) compared to controls, 37.4 ng/mL (IQR 11.7-65.7) (p < 0.0001). However, OPN levels on admission could not discriminate between mild and moderate-to-severe disease (132.6 ng/mL vs. 163.4 ng/mL). Nevertheless, the changes in OPN within 24 h of admission and Day 2/3 were higher among patients with moderate/severe AP (33.7%) compared to mild AP (-8.1%) (p = 0.01). This indicates that OPN is a relevant biomarker reflecting tissue injury in AP. The increase in OPN over time suggests that serial OPN measurements could contribute to the early detection of at-risk patients. Prospective studies assessing OPN in relation to outcome in AP are warranted.
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| 32. |
- Xin, Binbin, 1989-
(author)
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Synthesis of nanoporous Ca3Co4O9 thin films for flexible thermoelectrics
- 2020
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Licentiate thesis (other academic/artistic)abstract
- During energy generation, transportation and usage, large amounts of energy are lost as waste heat. With increasing energy consumption and environmental issues, exploiting this waste heat has drawn extensive attention. Thermoelectric energy conversion is an approach to take advantage of the ability of thermoelectric materials to convert waste heat into electricity.The thermoelectric effect was initially studied in the early 19th century with the discovery of the Seebeck effect. Thermoelectric materials and devices can directly convert thermal energy (temperature gradients) into electric energy (voltage) and vice versa. Thermoelectric devices have been used in space as energy generators and as coolers in small-scale instruments and devices. However, thermoelectrics remain limited in terms of applications. The traditional state-of-the-art thermoelectric materials, such as Bi2Te3, PbTe, and SnTe, exhibit high thermoelectric properties, but their disadvantages of toxicity, extreme rarity of tellurium, and oxidation when exposed to high temperature air restrict them from widespread use in applications. Compared to traditional thermoelectric materials, misfit-layered Ca3Co4O9 not only has the typical advantages of oxides including low cost, being environmentally friendly, and good chemical stability at high temperatures, but also has relatively high thermoelectric properties due to the complex structure which composed of CoO2 conductive layers and rock-salt type Ca2CoO3 insulating layers. Many strategies have been used to enhance the thermoelectric performance of Ca3Co4O9. Compared with bulk materials, thermoelectric thin films can exhibit improved thermoelectric properties and new application in flexible devices and miniaturization. Flexibility can be induced in Ca3Co4O9 by nanostructural tailoring to act as fully inorganic flexible thermoelectrics.In order to explore how to produce Ca3Co4O9 nanoporous thin film and control the porosity in the films, I have investigated the nanoporous Ca3Co4O9 system. Nanoporous Ca3Co4O9 thin films were synthesized using sequential reactive magnetron sputtering and post annealing to determine the key factors of nanoporous Ca3Co4O9 formation and tailoring of the porosity.
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