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1.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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  • Griswold, Max G., et al. (författare)
  • Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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  • Brunkwall, J., et al. (författare)
  • Endovascular Repair of Acute Uncomplicated Aortic Type B Dissection Promotes Aortic Remodelling: 1 Year Results of the ADSORB Trial
  • 2014
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 48:3, s. 285-291
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Uncomplicated acute type B aortic dissection (AD) treated conservatively has a 10% 30-day mortality and up to 25% need intervention within 4 years. In complicated AD, stent grafts have been encouraging. The aim of the present prospective randomised trial was to compare best medical treatment (BMT) with BMT and Gore TAG stent graft in patients with uncomplicated AD. The primary endpoint was a combination of incomplete/no false lumen thrombosis, aortic dilatation, or aortic rupture at 1 year. Methods: The AD history had to be less than 14 days, and exclusion criteria were rupture, impending rupture, malperfusion. Of the 61 patients randomised, 80% were DeBakey type IIIB. Results: Thirty-one patients were randomised to the BMT group and 30 to the BMT+TAG group. Mean age was 63 years for both groups. The left subclavian artery was completely covered in 47% and in part in 17% of the cases. During the first 30 days, no deaths occurred in either group, but there were three crossovers from the BMT to the BMT TAG group, all due to progression of disease within 1 week. There were two withdrawals from the BMT+TAG group. At the 1-year follow up there had been another two failures in the BMT group: one malperfusion and one aneurysm formation (p = .056 for all). One death occurred in the BMT TAG group. For the overall endpoint BMT+TAG was significantly different from BMT only (p < .001). Incomplete false lumen thrombosis, was found in 13 (43%) of the TAG+BMT group and 30 (97%) of the BMT group (p < .001). The false lumen reduced in size in the BMT+TAG group (p < .001) whereas in the BMT group it increased. The true lumen increased in the BMT TAG (p < .001) whereas in the BMT group it remained unchanged. The overall transverse diameter was the same at the beginning and after 1 year in the BMT group (42.1 mm), but in the BMT+TAG it decreased (38.8 mm; p = .062). Conclusions: Uncomplicated AD can be safely treated with the Gore TAG device. Remodelling with thrombosis of the false lumen and reduction of its diameter is induced by the stent graft, but long term results are needed. (C) 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
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  • Reitsma, Marissa B., et al. (författare)
  • Smoking prevalence and attributable disease burden in 195 countries and territories, 1990-2015 : a systematic analysis from the Global Burden of Disease Study 2015
  • 2017
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 389:10082, s. 1885-1906
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The scale-up of tobacco control, especially after the adoption of the Framework Convention for Tobacco Control, is a major public health success story. Nonetheless, smoking remains a leading risk for early death and disability worldwide, and therefore continues to require sustained political commitment. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) offers a robust platform through which global, regional, and national progress toward achieving smoking-related targets can be assessed. Methods We synthesised 2818 data sources with spatiotemporal Gaussian process regression and produced estimates of daily smoking prevalence by sex, age group, and year for 195 countries and territories from 1990 to 2015. We analysed 38 risk-outcome pairs to generate estimates of smoking-attributable mortality and disease burden, as measured by disability-adjusted life-years (DALYs). We then performed a cohort analysis of smoking prevalence by birth-year cohort to better understand temporal age patterns in smoking. We also did a decomposition analysis, in which we parsed out changes in all-cause smoking-attributable DALYs due to changes in population growth, population ageing, smoking prevalence, and risk-deleted DALY rates. Finally, we explored results by level of development using the Socio-demographic Index (SDI). Findings Worldwide, the age-standardised prevalence of daily smoking was 25.0% (95% uncertainty interval [UI] 24.2-25.7) for men and 5.4% (5.1-5.7) for women, representing 28.4% (25.8-31.1) and 34.4% (29.4-38.6) reductions, respectively, since 1990. A greater percentage of countries and territories achieved significant annualised rates of decline in smoking prevalence from 1990 to 2005 than in between 2005 and 2015; however, only four countries had significant annualised increases in smoking prevalence between 2005 and 2015 (Congo [Brazzaville] and Azerbaijan for men and Kuwait and Timor-Leste for women). In 2015, 11.5% of global deaths (6.4 million [95% UI 5.7-7.0 million]) were attributable to smoking worldwide, of which 52.2% took place in four countries (China, India, the USA, and Russia). Smoking was ranked among the five leading risk factors by DALYs in 109 countries and territories in 2015, rising from 88 geographies in 1990. In terms of birth cohorts, male smoking prevalence followed similar age patterns across levels of SDI, whereas much more heterogeneity was found in age patterns for female smokers by level of development. While smoking prevalence and risk-deleted DALY rates mostly decreased by sex and SDI quintile, population growth, population ageing, or a combination of both, drove rises in overall smoking-attributable DALYs in low-SDI to middle-SDI geographies between 2005 and 2015. Interpretation The pace of progress in reducing smoking prevalence has been heterogeneous across geographies, development status, and sex, and as highlighted by more recent trends, maintaining past rates of decline should not be taken for granted, especially in women and in low-SDI to middle-SDI countries. Beyond the effect of the tobacco industry and societal mores, a crucial challenge facing tobacco control initiatives is that demographic forces are poised to heighten smoking's global toll, unless progress in preventing initiation and promoting cessation can be substantially accelerated. Greater success in tobacco control is possible but requires effective, comprehensive, and adequately implemented and enforced policies, which might in turn require global and national levels of political commitment beyond what has been achieved during the past 25 years.
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  • Heyckendorf, J, et al. (författare)
  • Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model
  • 2021
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 58:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.MethodsAdult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.Results50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9–0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).ConclusionBiomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
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  • Redlinger-Pohn, Jakob D., et al. (författare)
  • Fines mobility and distribution in streaming fibre networks : experimental evidence and numerical modeling
  • 2020
  • Ingår i: Cellulose. - : Springer Science and Business Media B.V.. - 0969-0239 .- 1572-882X. ; 27:16, s. 9663-9682
  • Tidskriftsartikel (refereegranskat)abstract
    • The motion of flocculated fibres in a streaming suspension is governed by the balance of the network strength and hydrodynamic forces. With increasing flow rate through a channel, (1) the network initially occupying all space, (2) is then compressed to the centre, and (3) ultimately dispersed. This classical view neglects fibres-fines: we find that the distribution of these small particles differs in streaming suspensions. While it is known that fibre-fines can escape the fibre network, we find that the distribution of fibre-fines is non-homogenous in the network during compression: fibre-fines can be caged and retarded in the streaming fibre network. Hence, the amount of fibre-fines is reduced outside of a fibre network and enriched at the network’s interface. Aiming on selectively removing fibre-fines from a streaming network by suction, we identify a reduction of the fines removal rate. That documents a hindered mobility of fibre-fines when moving through the network of fibres. Additionally, we found evidence, that the mobility of fibre-fines is dependent on the fibre-fines quality, and is higher for fibrillar fines. Consequently, we suggest that the quality of fibre-fines removed from the suspension can be controlled with the flow regime in the channel. Finally, we present a phenomenological model to compute the length dependent fibre distribution in an arbitary geometry. For a fibre suspension channel flow we are able to predict a length-dependent fibre segregation near the channel’s centre. The erosion of a plug of long fibres was however underestimated by our model. Interestingly, our model with parameters fitted to streaming fibre suspension qualitatively agreed with the motion of micro-fibrillated cellulose. This gives hope that devices for handling flocculated fibre suspensions can be designed in the future with greater confidence. 
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  • Buker, P, et al. (författare)
  • Comparison of different stomatal conductance algorithms for ozone flux modelling
  • 2005
  • Ingår i: UNECE – Workshop “Critical Levels of Ozone: Further applying and developing the flux-based concept”, Obergurgl, 15-19 November 2005.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Two widely used algorithms for modelling stomatal conductance (gs) were compared in order to evaluate the approach leading to the most realistic predictions of stomatal fluxes to vegetated surfaces: a multiplicative algorithm initially developed by Jarvis (1976) and refined by Emberson et al. (2000) (DO3SE ) and a photosynthesis-based Ball&Berry-type algorithm developed by Nikolov et al. (1995) (LEAFC3). Both models were parameterised for several crop and tree species (wheat, grapevine, Scots pine, beech and birch) and have been applied to various datasets – with the main focus on wheat - representing different European regions (North, Central and South Europe). A sensitivity analysis has been carried out for both models to evaluate the dependence of gs on the meteorological parameters temperature, photosynthetic active radiation and vapour pressure deficit. Furthermore, in order to test whether a general species-specific parameterisation can account for differences in gs due to plants growing under different climatic conditions throughout Europe, the models have been re-parameterised for local meteorological conditions. A direct comparison of both models showed that the net photosynthetic-based model required more detailed meteorological (e.g. ambient CO2-concentration, dew-point temperature) and plant-physiological (e.g. Vcmax and Jmax) input parameters while not delivering a substantially higher R2 when comparing measured and modelled gs. The relative weakness of the multiplicative model lies in its dependence on the maximum stomatal conductance (gmax), whereas the photosynthesis-based model is not taking into account phenology-related changes in gs. Furthermore, the results show that an equally close relationship between gs and net photosynthetic rate throughout the entire growing season is questionable. We conclude that the multiplicative approach is favourable for calculating stomatal fluxes on a wider scale (e.g. within EMEP-deposition model), whereas the photosynthesis-based approach is a potential alternative for modelling fluxes on a local scale.
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  • Buker, P., et al. (författare)
  • DO3SE modelling of soil moisture to determine ozone flux to forest trees
  • 2012
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:12, s. 5537-5562
  • Tidskriftsartikel (refereegranskat)abstract
    • The DO3SE (Deposition of O-3 for Stomatal Exchange) model is an established tool for estimating ozone (O-3) deposition, stomatal flux and impacts to a variety of vegetation types across Europe. It has been embedded within the EMEP (European Monitoring and Evaluation Programme) photochemical model to provide a policy tool capable of relating the flux-based risk of vegetation damage to O-3 precursor emission scenarios for use in policy formulation. A key limitation of regional flux-based risk assessments has been the assumption that soil water deficits are not limiting O-3 flux due to the unavailability of evaluated methods for modelling soil water deficits and their influence on stomatal conductance (g(sto)), and subsequent O-3 flux. This paper describes the development and evaluation of a method to estimate soil moisture status and its influence on g(sto) for a variety of forest tree species. This DO3SE soil moisture module uses the Penman-Monteith energy balance method to drive water cycling through the soil-plant-atmosphere system and empirical data describing g(sto) relationships with pre-dawn leaf water status to estimate the biological control of transpiration. We trial four different methods to estimate this biological control of the transpiration stream, which vary from simple methods that relate soil water content or potential directly to g(sto), to more complex methods that incorporate hydraulic resistance and plant capacitance that control water flow through the plant system. These methods are evaluated against field data describing a variety of soil water variables, g(sto) and transpiration data for Norway spruce (Picea abies), Scots pine (Pinus sylvestris), birch (Betula pendula), aspen (Populus tremuloides), beech (Fagus sylvatica) and holm oak (Quercus ilex) collected from ten sites across Europe and North America. Modelled estimates of these variables show consistency with observed data when applying the simple empirical methods, with the timing and magnitude of soil drying events being captured well across all sites and reductions in transpiration with the onset of drought being predicted with reasonable accuracy. The more complex methods, which incorporate hydraulic resistance and plant capacitance, perform less well, with predicted drying cycles consistently underestimating the rate and magnitude of water loss from the soil. A sensitivity analysis showed that model performance was strongly dependent upon the local parameterisation of key model drivers such as the maximum g(sto), soil texture, root depth and leaf area index. The results suggest that the simple modelling methods that relate g(sto) directly to soil water content and potential provide adequate estimates of soil moisture and influence on g(sto) such that they are suitable to be used to assess the potential risk posed by O-3 to forest trees across Europe.
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  • Durual, S, et al. (författare)
  • Pre-Treat Xenogenic Collagenous Blocks of Bone Substitutes with Saline Facilitate Their Manipulation and Guarantee High Bone Regeneration Rates, Qualitatively and Quantitatively
  • 2021
  • Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Deproteinized bovine bone mineral particles embedded in collagen (DBBM-C) are widely used for bone regenerations with excellent, albeit sometimes variable clinical outcomes. Clinicians usually prepare DBBM-C by mixing with blood. Replacing blood by saline represents an alternative. We investigated if saline treatment could improve DBBM-C i. handling in vitro and ii. biological performances in a rabbit calvarial model. In vitro, DBBM-C blocks soaked in saline or blood were submitted to compression tests. In vivo, four poly ether ether ketone (PEEK)cylinders were placed on 16 rabbit skulls, filled with DBBM-C soaked in blood or saline for 2–4–8–12 weeks before histomorphometry. DBBM-C blocks were fully hydrated after 30 s in saline when 120 s in blood could not hydrate blocks core. Stiffness gradually decreased 2.5-fold after blood soaking whereas a six-fold decrease was measured after 30 s in saline. In vivo, saline treatment allowed 50% more bone regeneration during the first month when compared to blood soaking. This difference was then no longer visible. New bone morphology and maturity were equivalent in both conditions. DBBM-C saline-soaking facilitated its handling and accelerated bone regeneration of highly qualitative tissues when compared to blood treatment. Saline pretreatment thus may increase the clinical predictability of bone augmentation procedures.
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  • Feuerbacher, M., et al. (författare)
  • The Samson phase, β-Mg2Al3, Revisited
  • 2007
  • Ingår i: Zeitschrift für Kristallographie. - 0044-2968. ; 222:6, s. 259-288
  • Tidskriftsartikel (refereegranskat)
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  • George, Julie, et al. (författare)
  • Comprehensive genomic profiles of small cell lung cancer
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
  • Tidskriftsartikel (refereegranskat)abstract
    • We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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  • Karlsson, Per Erik, 1957, et al. (författare)
  • Risk assessments for forest trees: The performance of the ozone flux versus the AOT concepts
  • 2007
  • Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 146:3, s. 608-616
  • Tidskriftsartikel (refereegranskat)abstract
    • Published ozone exposure-response relationships from experimental studies with young trees performed at different sites across Europe were re-analysed in order to test the performance of ozone exposure indices based on AOTX (Accumulated exposure Over a Threshold of X nmol mol(-1)) and AF(st)Y (Accumulated Stomatal Flux above a threshold of Y nmol m(-2) s(-1)). AF(st)1.6 was superior, as compared to AOT40, for explaining biomass reductions, when ozone sensitive species with differing leaf morphology were included in the analysis, while this was not the case for less sensitive species. A re-analysis of data with young black cherry trees, subject to different irrigation regimes, indicated that leaf visible injuries were more strongly related to the estimated stomatal ozone uptake, as compared to the ozone concentration in the air. Experimental data with different clones of silver birch indicated that leaf thickness was also an important factor influencing the development of ozone induced leaf visible injury. (c) 2006 Elsevier Ltd. All rights reserved.
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  • Lange, C., et al. (författare)
  • Perspectives for personalized therapy for patients with multidrug-resistant tuberculosis
  • 2018
  • Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 284:2, s. 163-188
  • Forskningsöversikt (refereegranskat)abstract
    • According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.
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  • Popall, M, et al. (författare)
  • ORMOCER (R) S - Inorganic-organic hybrid materials for e/o-interconnection-technology
  • 2000
  • Ingår i: Molecular Crystals and Liquid Crystals Science and Technology. - 1058-725X. ; 354, s. 711-730
  • Tidskriftsartikel (refereegranskat)abstract
    • Hybrid inorganic-organic polymers (ORMOCER (R)s) have been developed and tested for evaluation in optical and electrical interconnection technology. The photopatternable materials with negative resist behaviour are composed of inorganic oxidic structures cross-linked or substituted by organic groups. They are prepared from organosilane precursors by sol-gel-processing in combination with organic crosslinking of polymerizable organic Functions, As a result of these functionalities the properties of the ORMOCER (R)s can be adjusted to particular applications. Systematic variation of composition combined with adaptation to micro system technology allows great flexibility in processing. The main features of these materials are: Combined use as dielectric and passivation layers in electrical systems and devices as well as core and cladding for optical applications enables e/o applications with high integration levels, Postbaking at moderate temperatures (120 degreesC - 170 degreesC) enables processing on low-cost substrates such as FR-4 and BT. Easily adaptable to thin film technology: spin-on with planarisation >90% and via diameters down to 20 mum have been achieved.
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  • Sapkota, Ram P., et al. (författare)
  • Internet-delivered therapy for alcohol misuse : engagement, satisfaction, and outcomes when patients select their preference for therapist- or self-guided treatment
  • 2024
  • Ingår i: Addiction science & clinical practice. - 1940-0632 .- 1940-0640. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Alcohol misuse is common and causes substantial harm. Internet-delivered cognitive behaviour therapy (ICBT) is effective in reducing alcohol misuse; however, the literature investigating how treatment outcomes are impacted by patients’ preferences for therapist- versus self-guided ICBT for alcohol misuse is sparse.Methods In this preference trial, 74 eligible patients (who reported ≥ 14 drinks in the previous week and obtained scores suggesting hazardous or harmful drinking) chose between enrolling in either therapist- or self-guided ICBT for alcohol misuse. We investigated whether those who chose therapist- versus self-guided ICBT differed in their (a) drinking outcomes—as measured by Timeline Follow-Back (TLFB) and heavy drinking days (HDD) at post-treatment and 3-month follow-up—and (b) post-treatment ICBT engagement and satisfaction.Results The majority (81.1%) of eligible patients chose therapist-guided ICBT. These patients reported higher psychotropic medication use, drinking difficulties, and anxiety symptoms. For both the therapist- and self-guided patients, a modified intention-to-treat analysis revealed large within-group treatment effects for TLFB (β =  − 2.64, SE 0.66; p < 0.001) and HDD (β =  − 0.34, SE 0.07; p < 0.001), with large pre-to-post-treatment Cohen’s effect sizes of d = 0.97 (95% CI [0.49, 1.45]) for TLFB and d = 1.19 (95% CI [0.69, 1.68]) for HDD. The interaction comparing the effects of therapist- to self-guided ICBT over time was not significant for TLFB (p = 0.34) or HDD (p = 0.06). With treatment, for both therapist- and self-guided patients, there was a significant improvement in drinking difficulties, cravings, and confidence with controlling cravings, as well as in anxiety, depression, and functional impairment. Further, the majority (75.7%) of patients completed five or more lessons, as well as reported overall satisfaction with the treatment (88.9%) and increased confidence in managing their symptoms (86.7%); these outcomes also did not differ between therapist- and self-guided patients.Conclusions The current study shows that ICBT for alcohol misuse is associated with reduced drinking and comorbid mental health difficulties over time, irrespective of whether patients chose to complete the course on their own or with therapist guidance.
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  • Sourikopoulos, Ilias, et al. (författare)
  • The H2020-SPACE-SIPHODIAS project: Space-grade optoelectronic interfaces for photonic digital and analogue very-high-throughput satellite payloads
  • 2021
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11852
  • Konferensbidrag (refereegranskat)abstract
    • The EU-SIPhoDiAS project deals with the development of critical photonic building blocks needed for high-performance and low size, weight, and power (SWaP) photonics-enabled Very High Throughput Satellites (VHTS). In this presentation, we report on the design and fabrication activities during the first year of the project concerning the targeted family of digital and microwave photonic components. This effort aims to demonstrate components of enhanced reliability at technology readiness level (TRL) 7. Specifically, with respect to microwave photonic links, we report: (i) the design of Ka and Q-bands analogue photodetectors that will be assembled in compact packages, allowing for very high bandwidth per unit area and (ii) on the design of compact V-band GaAs electro-optic modulator arrays, which use a folded-path optical configuration to manage all fiber interfaces packaged opposite direct in-line RF feeds for ease of board layouts and mass/size benefits. With respect to digital links, we report on the development of 100 Gb/s (4 x 25 Gb/s) digital optical transceiver sub-assemblies developed using flip-chip mounting of electronic and opto-parts on a high-reliability borosilicate substrate. The transceiver chipset developed specifically for this project refers to fully-custom 25 Gb/s radiation hard (RH) VCSEL driver and TIA ICs designed in IHP’s 130 nm SiGe BiCMOS Rad-Hard process.
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  • Sundström, Christopher, et al. (författare)
  • Optimizing internet-delivered cognitive behaviour therapy for alcohol misuse : a randomized factorial trial examining effects of a pre-treatment assessment interview and guidance
  • 2022
  • Ingår i: Addiction science & clinical practice. - : Springer Science and Business Media LLC. - 1940-0632 .- 1940-0640. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Internet-delivered cognitive behavioral therapy (ICBT) for alcohol misuse has potential to radically improve access to evidence-based care, and there is a need to investigate ways to optimize its delivery in clinical settings. Guidance from a clinician has previously been shown to improve drinking outcomes in ICBT, and some studies suggest that pre-treatment assessments may contribute in initiating early change. The objective of this study was to investigate the added and combined effects of a pre-treatment assessment interview and guidance on the outcomes of ICBT for alcohol misuse delivered in an online therapy clinic.Methods: A 2X2 factorial randomized controlled trial was conducted where participants received access to an 8-week ICBT program, and either a pre-treatment assessment interview (Factor 1), guidance (Factor 2), a combination of these, or neither of these. Participants were 270 individuals (66.8% female, mean age = 46.5) scoring 8 or more on the Alcohol Use Disorders Identification Test and consuming 14 standard drinks or more in the preceding week. Primary outcomes were number of drinks consumed and number of heavy drinking days during the preceding week, 3 months post-treatment.Results: Large within-group effects were found in terms of alcohol reductions (dw ≥ 0.82, p < 0.001), but neither of the factors significantly improved drinking outcomes. Guidance was associated with greater adherence (i.e. completed modules).Conclusions: Neither a pre-treatment assessment interview nor guidance from a clinician appears to improve drinking outcomes resulting from internet-delivered cognitive behaviour therapy for alcohol misuse when delivered in a routine online therapy clinic.
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