| 1. |
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| 2. |
- Hageman, Steven H. J., et al.
(författare)
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Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease : the updated SMART2 algorithm
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:18, s. 1715-1727
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Tidskriftsartikel (refereegranskat)abstract
- Aims The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations.Methods and results Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options.Conclusion The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.
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| 8. |
- Gennemark, Peter, et al.
(författare)
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An oral antisense oligonucleotide for PCSK9 inhibition
- 2021
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:593
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
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| 9. |
- Jonsson, C. E., et al.
(författare)
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High-resolution diatom d18O records from two sub-Arctic high-altitude lakes in the Swedish Scandes
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Ingår i: Journal of Quaternary Science. - 0267-8179 .- 1099-1417.
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Tidskriftsartikel (refereegranskat)abstract
- Waters from high altitude alpine lakes are mainly recharged by meteoric water. Because of seasonal variations in precipitation and temperature, and relatively short hydraulic residence times, most high altitude lakes have lake water isotopic compositions (δ18Olake) that fluctuate due to seasonality in water balance processes. Input from snowmelt, in particular, has a significant role in determining lake water d18O. Here we compare two high resolution δ18Odiatom records from lake sediments in the Swedish Scandes with instrumental data from the last century obtained from nearby meteorological stations. The time period AD 1900 to AD 1990 is characterized by an increase in winter precipitation and high winter/summer precipitation ratios and this is recorded in δ18Odiatom as decreasing trends. Lowest δ18Odiatom values and highest amount of winter precipitation are found around AD 1990 when the winter North Atlantic Oscillation index was above +2. We conclude that for the last 150 years the main factor affecting the δ18Odiatom signal in these sub-Arctic high altitude lakes with short residence times has been changes in amount of winter precipitation and that δ18Odiatom derived from high altitude lakes in the Swedish Scandes can be used as a winter precipitation proxy.
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| 10. |
- Jonsson, Christina E., et al.
(författare)
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High-resolution diatom delta O-18 records, from the last 150 years, reflecting changes in amount of winter precipitation in two sub-Arctic high-altitude lakes in the Swedish Scandes
- 2010
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 25:6, s. 918-930
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Tidskriftsartikel (refereegranskat)abstract
- Waters from high-altitude alpine lakes are mainly recharged by meteoric water. Because of seasonal variations in precipitation and temperature and relatively short hydraulic residence times, most high-altitude lakes have lake water isotopic compositions (delta O-18(lake)) that fluctuate due to seasonality in water balance processes. Input from snowmelt, in particular, has a significant role in determining lake water delta O-18. Here we compare two high-resolution delta O-18(diatom) records from lake sediments in the Swedish Scandes with instrumental data from the last century obtained from nearby meteorological stations. The time period AD 1900-1990 is characterised by an increase in winter precipitation and high winter/summer precipitation ratios and this is recorded in delta O-18(diatom) as decreasing trends. Lowest delta O-18(diatom) values and highest amount of winter precipitation are found around AD 1990 when the winter North Atlantic Oscillation index was above +2. We conclude that for the last 150 a the main factor affecting the delta O-18(diatom) signal in these sub-Arctic high-altitude lakes with short residence times has been changes in amount of winter precipitation and that delta O-18(diatom) derived from high-altitude lakes in the Swedish Scandes can be used as a winter precipitation proxy.
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| 11. |
- Jonsson, Christina E, et al.
(författare)
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High resolution diatom δ18O records from two sub-Arctic high altitude lakes in the Swedish Scandes
- 2010
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 25:6, s. 918-930
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Tidskriftsartikel (refereegranskat)abstract
- Waters from high-altitude alpine lakes are mainly recharged by meteoric water. Because of seasonal variations in precipitation and temperature and relatively short hydraulic residence times, most high-altitude lakes have lake water isotopic compositions (δ18Olake) that fluctuate due to seasonality in water balance processes. Input from snowmelt, in particular, has a significant role in determining lake water δ18O. Here we compare two high-resolution δ18Odiatom records from lake sediments in the Swedish Scandes with instrumental data from the last century obtained from nearby meteorological stations. The time period AD 1900–1990 is characterised by an increase in winter precipitation and high winter/summer precipitation ratios and this is recorded in δ18Odiatom as decreasing trends. Lowest δ18Odiatom values and highest amount of winter precipitation are found around AD 1990 when the winter North Atlantic Oscillation index was above +2. We conclude that for the last 150 a the main factor affecting the δ18Odiatom signal in these sub-Arctic high-altitude lakes with short residence times has been changes in amount of winter precipitation and that δ18Odiatom derived from high-altitude lakes in the Swedish Scandes can be used as a winter precipitation proxy. Copyright © 2010 John Wiley & Sons, Ltd.
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| 14. |
- Banks, H. T., et al.
(författare)
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Modeling bumble bee population dynamics with delay differential equations
- 2017
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Ingår i: Ecological Modelling. - : Elsevier BV. - 0304-3800. ; 351, s. 14-23
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Tidskriftsartikel (refereegranskat)abstract
- Bumble bees are ubiquitous creatures and crucial pollinators to a vast assortment of crops worldwide. Bumble bee populations have been decreasing in recent decades, with demise of flower resources and pesticide exposure being two of several suggested pressures causing declines. Many empirical investigations have been performed on bumble bees and their natural history is well documented, but the understanding of their population dynamics over time, causes for observed declines, and potential benefits of management actions is poor. To provide a tool for projecting and testing sensitivity of growth of populations under contrasting and combined pressures, we propose a delay differential equation model that describes multi-colony bumble bee population dynamics. We explain the usefulness of delay equations as a natural modeling formulation, particularly for bumble bee modeling. We then introduce a particular numerical method that approximates the solution of the delay model. Next, we provide simulations of seasonal population dynamics in the absence of pressures. We conclude by describing ways in which resource limitation, pesticide exposure and other pressures can be reflected in the model.
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| 15. |
- Bondarenko, Vasyl, et al.
(författare)
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Structures of highly flexible intracellular domain of human alpha 7 nicotinic acetylcholine receptor
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The intracellular domain (ICD) of Cys-loop receptors mediates diverse functions. To date, no structure of a full-length ICD is available due to challenges stemming from its dynamic nature. Here, combining nuclear magnetic resonance (NMR) and electron spin resonance experiments with Rosetta computations, we determine full-length ICD structures of the human alpha 7 nicotinic acetylcholine receptor in a resting state. We show that similar to 57% of the ICD residues are in highly flexible regions, primarily in a large loop (loop L) with the most mobile segment spanning similar to 50 angstrom from the central channel axis. Loop L is anchored onto the MA helix and virtually forms two smaller loops, thereby increasing its stability. Previously known motifs for cytoplasmic binding, regulation, and signaling are found in both the helices and disordered flexible regions, supporting the essential role of the ICD conformational plasticity in orchestrating a broad range of biological processes.
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| 16. |
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| 17. |
- Jogestrand, T., et al.
(författare)
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Equalis kriterier för karotisdiagnostik – under kontinuerlig uppgradering
- 2012
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:13, s. 702-703
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Tidskriftsartikel (refereegranskat)abstract
- Ultraljudsundersökning av karotisartärerna med så kallad duplexteknik har använts i Sverige sedan början av 1980-talet. Equalis expertgrupp för fysiologisk kärldiagnostik har nyligen presenterat sina rekommendationer för karotisdiagnostik med ultraljudsteknik.
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| 18. |
- Kaislahti Tillman, Päivi, 1958-, et al.
(författare)
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Long-term climate variability in continental subarctic Canada : A 6200-year record derived from stable isotopes in peat
- 2010
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 298:3, s. 235-246
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Tidskriftsartikel (refereegranskat)abstract
- The rapid warming of arctic regions during recent decades has been recorded by instrumental monitoring, but the natural climate variability in the past is still sparsely reconstructed across many areas. We have reconstructed past climate changes in subarctic west-central Canada. Stable carbon and oxygen isotope ratios (δ13C, δ18O) were derived from a single Sphagnum fuscum plant component; α-cellulose isolated from stems. Periods of warmer and cooler conditions identified in this region, described in terms of a “Mediaeval Climatic Anomaly” and “Little Ice Age” were registered in the temperature reconstruction based on the δ13C record. Some conclusions could be drawn about wet/dry shifts during the same time interval from the δ18O record, humification indices and the macrofossil analysis. The results were compared with other proxy data from the vicinity of the study area. The amplitude of the temperature change was similar to that in chironomid based reconstructions, showing c. 6.5±2.3°C variability in July temperatures during the past 6.2 ka.
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| 19. |
- Kaislahti Tillman, Päivi, 1958-, et al.
(författare)
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Stable carbon and oxygen isotopes in Sphagnum fuscum peat from subarctic Canada : implications for palaeoclimate studies
- 2010
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Ingår i: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 270:1-4, s. 216-226
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Tidskriftsartikel (refereegranskat)abstract
- Stable carbon and oxygen isotope ratios in single plant components in Sphagnum peat have a good potential to reveal environmental changes in peat archives. Two peat profiles, covering the past ~6000 years, and a Sphagnum hummock from a discontinuous permafrost area in west central Canada were studied in order to evaluate the effect of decomposition rate on isotope records and to assess which plant components are most suitable for climate reconstructions. The stable isotope values from the most recently forming Sphagnum tissues were compared with observational climate data to study the impact of variations in temperature and precipitation on the peat isotopes. Our results show that there is high correlation between δ13C values in α-cellulose isolated from Sphagnum fuscum stems and summer temperatures, whereas δ18O in the plant tissues is controlled by several factors, such as summer precipitation, summer temperature and evaporation. According to our results, decomposition as derived from C/N values and colorimetry does not seem to affect the oxygen and carbon isotope values of α-cellulose from Sphagnum fuscum peat significantly. There is, however, a (quasi-) constant offset between the isotope values of branches and stems and between whole plant material and α-cellulose, which makes it crucial to select single moss-fractions when past climate and environmental changes are to be derived from the isotope record.
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| 20. |
- Svanberg, Sune, et al.
(författare)
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Applications of terawatt lasers
- 1994
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Ingår i: LASER SPECTROSCOPY - XITH INTERNATIONAL CONFERENCE. - : AIP. - 1551-7616 .- 0094-243X. - 1563962624 ; :290, s. 264-269
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Konferensbidrag (refereegranskat)
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| 21. |
- Tillman, Carin, et al.
(författare)
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A Longitudinal Examination of the Developmental Executive Function Hierarchy in Children With Externalizing Behavior Problems
- 2015
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Ingår i: Journal of Attention Disorders. - : SAGE Publications. - 1087-0547 .- 1557-1246. ; 19:6, s. 496-506
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Using a 4-year longitudinal design, we evaluated two hypotheses based on developmental executive function (EF) hierarchy accounts in a sample of children with externalizing problems. Method: The participants performed EF tasks when they were between 8 and 12 years (M = 9.93), and again approximately 4 years later when they were between 12 and 15 years (M = 13.36). Results: Inhibition in middle childhood predicted working memory (WM) 4 years later. Further, deficits in inhibition and sustained attention were more prominent in middle rather than late childhood, whereas poor WM was salient throughout these periods. Conclusions: These findings support the hypotheses that EFs develop hierarchically and that EF deficits in ADHD are more prominent in actively developing EFs. They also emphasize ADHD as a developmental disorder.
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| 22. |
- Tillman, Carin, et al.
(författare)
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Intellectual deficits in children with ADHD beyond central executive and non-executive functions
- 2009
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Ingår i: Archives of clinical neuropsychology. - : Oxford University Press (OUP). - 0887-6177 .- 1873-5843. ; 24:8, s. 769-782
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to specify the deficit in intellectual ability in children with attention deficit hyperactivity disorder (ADHD), by studying the mediating role of impairments in central executive function (EF)-related components (working memory, inhibition, sustained attention) and non-EFs (short-term memory and processing speed). Two hundred and thirty children aged 8-11 years from a population-based sample were assigned to either the ADHD group, the clinical comparison group, or the normal comparison group. The results showed that children with ADHD had poorer fluid and crystallized intelligence, relative to both comparison groups. Further, regarding fluid intelligence, these deficits were not fully mediated by, but rather went beyond, poorer functioning on the studied EF-related components and non-EFs. We tentatively interpret these fluid deficits in children with ADHD as representing deficiencies in a general intellectual resource reflecting executive attentional processes. Concerning crystallized ability, in contrast, the deficit signified impairment in the studied cognitive functions, as indicated by the significant full mediation effect.
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| 23. |
- Tillman, Carin M., et al.
(författare)
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Intelligence and Specific Cognitive Abilities in Children
- 2009
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Ingår i: Journal of Individual Differences. - : Hogrefe Publishing Group. - 1614-0001 .- 2151-2299. ; 30:4, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- This community-based study investigated the relationships between measures of specific cognitive functions (such as working memory [WM] and interference control) and intelligence in 283 8- to 11-year-old children, including 124 children who fulfilled criteria for a psychiatric diagnosis. A hierarchical regression analysis was used to overcome issues of overlapping predictor constructs. The results generally showed that measures of processing speed, WM, as well as inhibitory interference control entered in the order of presentation, each contributed uniquely to the explanation of fluid intelligence performance. The results for crystallized intelligence performance generally showed that the measures of processing speed, short-term memory ( STM), WM, and sustained attention-entered in that order-made significant independent contributions. While effect sizes varied somewhat for contributions in the whole sample compared with the subgroup not meeting criteria for a psychiatric diagnosis, there were no significant differences. The findings therefore should be broadly representative in indicating that the unique aspects of these cognitive functions are important in the explanation of intelligence. The findings also demonstrate important independent features of the functions used as predictors.
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| 25. |
- Tillman, K. A., et al.
(författare)
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Low-threshold femtosecond optical parametric oscillator based on chirped-pulse frequency conversion
- 2003
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Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 28:7, s. 543-545
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Tidskriftsartikel (refereegranskat)abstract
- We report what is to our knowledge the first demonstration of a femtosecond optical parametric oscillator based on chirped-pulse frequency conversion in a long crystal of aperiodically poled potassium titanyl phosphate. The minimum pump threshold power was 15 mW, and a signal slope efficiency of 35% was achieved. Continuous tuning from 1190 to 1450 nm was obtained for an average pump power of 800 mW.
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| 26. |
- Tillman, K. A., et al.
(författare)
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Low-threshold, high-repetition-frequency femtosecond optical parametric oscillator based on chirped-pulse frequency conversion
- 2003
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Ingår i: Journal of the Optical Society of America. B, Optical physics. - 0740-3224 .- 1520-8540. ; 20:6, s. 1309-1316
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Tidskriftsartikel (refereegranskat)abstract
- We report a quasi-phase-matched optical parametric oscillator that incorporates a chirped nonlinear crystal and uses prechirped pulses matched to the crystal chirp to improve the conversion efficiency and reduce the operational threshold. A 20-mm crystal of aperiodically poled KTiOPO4 is phase matched to stretched Ti:sapphire pump pulses. The Ti:sapphire laser produces 104-MHz output pulses at 850 nm that are stretched from 190 to 900 fs with an average output power of 750 mW The system has demonstrated a pump depletion of more than 80%, a signal slope efficiency of 35%, and a threshold of 14.4 mW The cavity showed tuning from 1194 to 1455 nm. over a length range of 130 mum. The approach described demonstrates the potential of using chirped-pulse-chirped-crystal quasi-phase matching in long nonlinear crystals as a method to reduce ultrafast optical parametric oscillator thresholds.
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