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  • 2019
  • Tidskriftsartikel (refereegranskat)
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6.
  • 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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7.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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8.
  • Abele, H., et al. (författare)
  • Particle physics at the European Spallation Source
  • 2023
  • Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
  • Forskningsöversikt (refereegranskat)abstract
    • Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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9.
  • Tinetti, Giovanna, et al. (författare)
  • The EChO science case
  • 2015
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
  • Tidskriftsartikel (refereegranskat)abstract
    • The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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10.
  • Nicolas, Aude, et al. (författare)
  • Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
  • 2018
  • Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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11.
  • Eskelund, Christian W., et al. (författare)
  • 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2) : prolonged remissions without survival plateau
  • 2016
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 175:3, s. 410-418
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
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12.
  • Munch, Marie W., et al. (författare)
  • Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial
  • 2021
  • Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817
  • Tidskriftsartikel (refereegranskat)abstract
    • Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
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13.
  • Schunkert, Heribert, et al. (författare)
  • Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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14.
  • van Rheenen, Wouter, et al. (författare)
  • Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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15.
  • Assimes, Themistocles L., et al. (författare)
  • Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
  • 2010
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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16.
  • Breznau, Nate, et al. (författare)
  • Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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17.
  • Eskelund, Christian W., et al. (författare)
  • TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
  • 2017
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
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18.
  • Gommenginger, Christine, et al. (författare)
  • SEASTAR: A mission to study ocean submesoscale dynamics and small-scale atmosphere-ocean processes in coastal, shelf and polar seas
  • 2019
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUL
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • High-resolution satellite images of ocean color and sea surface temperature reveal an abundance of ocean fronts, vortices and filaments at scales below 10 km but measurements of ocean surface dynamics at these scales are rare. There is increasing recognition of the role played by small scale ocean processes in ocean-atmosphere coupling, upper-ocean mixing and ocean vertical transports, with advanced numerical models and in situ observations highlighting fundamental changes in dynamics when scales reach 1 km. Numerous scientific publications highlight the global impact of small oceanic scales on marine ecosystems, operational forecasts and long-term climate projections through strong ageostrophic circulations, large vertical ocean velocities and mixed layer re-stratification. Small-scale processes particularly dominate in coastal, shelf and polar seas where they mediate important exchanges between land, ocean, atmosphere and the cryosphere e.g. freshwater, pollutants. As numerical models continue to evolve towards finer spatial resolution and increasingly complex coupled atmosphere-wave-ice-ocean systems, modern observing capability lags behind, unable to deliver the high-resolution synoptic measurements of total currents, wind vectors and waves needed to advance understanding, develop better parameterizations and improve model validations, forecasts and projections. SEASTAR is a satellite mission concept that proposes to directly address this critical observational gap with synoptic two-dimensional imaging of total ocean surface current vectors and wind vectors at 1 km resolution and coincident directional wave spectra. Based on major recent advances in squinted along-track Synthetic Aperture Radar interferometry, SEASTAR is an innovative, mature concept with unique demonstrated capabilities, seeking to proceed towards spaceborne implementation within Europe and beyond.
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19.
  • Hansen, Lone, et al. (författare)
  • Anatomy and biomechanics of the back muscles in the lumbar spine with reference to biomechanical modeling
  • 2006
  • Ingår i: Spine. - 0362-2436. ; 31:17, s. 1888-1899
  • Forskningsöversikt (refereegranskat)abstract
    • Study Design. This article describes the development of a musculoskeletal model of the human lumbar spine with focus on back muscles. It includes data from literature in a structured form. Objective. To review the anatomy and biomechanics of the back muscles related to the lumbar spine with relevance for biomechanical modeling. Summary of Background Data. To reduce complexity, muscle units have been incorporated in an abridged manner, reducing their actions more or less to a single force equivalent. In early models of the lumbar spine, this may have been a necessary step to reduce complexity and, thereby, calculation time. The muscles of the spine are well described in the literature, but mainly qualitatively. Most of the literature provides a description of the structures without precise data of fiber length, muscle length, cross-sectional areas, moment arms, forces, etc. The predicted output of musculoskeletal models is very much dependent on the input parameters. The information needed to improve models consists of better approximations of the attachments to the vertebrae, and more precise data. Method. Review of literature. Results. The predicted output of musculoskeletal models is very much dependent on the input parameters. Moderate changes in the assumed muscle line-of-action (i.e., moment arm) could substantially alter the magnitudes of predicted muscle and spinal forces, while the choice of optimization formulation is less sensitive. Conclusions. Input parameters, moment arms, as well as physiologic cross-sectional areas have a profound effect on the predicted muscle forces. Therefore, it is important to choose the values for moment arm and physiologic cross-sectional area carefully because they are essential input parameters to biomechanical models.
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20.
  • Ostergaard, Henrik, et al. (författare)
  • Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide
  • 2011
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:8, s. 2333-2341
  • Tidskriftsartikel (refereegranskat)abstract
    • Current management of hemophilia B entails multiple weekly infusions of factor IX (FIX) to prevent bleeding episodes. In an attempt to make a longer acting recombinant FIX (rFIX), we have explored a new releasable protraction concept using the native N-glycans in the activation peptide as sites for attachment of polyethylene glycol (PEG). Release of the activation peptide by physiologic activators converted glycoPEGylated rFIX (N9-GP) to native rFIXa and proceeded with normal kinetics for FXIa, while the Km for activation by FVIIa-tissue factor (TF) was increased by 2-fold. Consistent with minimal perturbation of rFIX by the attached PEG, N9-GP retained 73%-100% specific activity in plasma and whole-blood-based assays and showed efficacy comparable with rFIX in stopping acute bleeds in hemophilia B mice. In animal models N9-GP exhibited up to 2-fold increased in vivo recovery and a markedly prolonged half-life in mini-pig (76 hours) and hemophilia B dog (113 hours) compared with rFIX (16 hours). The extended circulation time of N9-GP was reflected in prolonged correction of coagulation parameters in hemophilia B dog and duration of effect in hemophilia B mice. Collectively, these results suggest that N9-GP has the potential to offer efficacious prophylactic and acute treatment of hemophilia B patients at a reduced dosing frequency. (Blood. 2011; 118(8): 2333-2341)
  •  
21.
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22.
  • Williamson, Alice, et al. (författare)
  • Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
  • 2023
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
  • Tidskriftsartikel (refereegranskat)abstract
    • Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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23.
  • Zeggini, Eleftheria, et al. (författare)
  • Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
  • 2008
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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24.
  • Ahmed, Niaz, et al. (författare)
  • Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018.
  • 2019
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 4:4, s. 307-317
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at www.eso-karolinska.org and http://eso-stroke.org) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.
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25.
  • Allentoft, Morten E., et al. (författare)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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26.
  • Andersen, Christian B., et al. (författare)
  • Pythium oligandrum induces growth promotion in starch potato without significantly altering the rhizosphere microbiome
  • 2024
  • Ingår i: Applied Soil Ecology. - 0929-1393. ; 199
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant health promoting organisms, including microbial biological control agents, are of increasing importance for the development of more sustainable agriculture. To understand the function of these microbes as biological control agents under field conditions and their overall impact on soil and plant health, we need to learn more about the impact of plant beneficial microbes on the rhizosphere microbiome of crops such as potato. The plant beneficial oomycete Pythium oligandrum has previously been reported both as a biocontrol agent and as a plant growth promoter, or biostimulant, in several crop species. To investigate the potential of P. oligandrum as a biostimulant in potato, we performed a series of controlled-environment bioassays in three cultivars. We showed that biostimulation of potato by P. oligandrum is plant genotype-specific. We confirmed the biostimulation by P. oligandrum in the starch potato cultivar Kuras under field conditions. We further investigated the effects of P. oligandrum on the potato rhizosphere microbiome, sampling individual potato plants at three time points over the growing season (representing the vegetative growth phase, flowering, and the onset of senescence). Metabarcoding using ITS and 16S amplicon sequencing revealed no significant overall effect of P. oligandrum application on the bacterial and fungal rhizosphere communities. However, some genera were significantly differentially abundant after P. oligandrum application, including some classified as plant-beneficial microbes. We conclude that P. oligandrum has a cultivar-dependent growth-promoting effect in potato and only minor effects on the rhizosphere microbiome.
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27.
  • Andersen, Ken, et al. (författare)
  • B-10 multi-grid proportional gas counters for large area thermal neutron detectors
  • 2013
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 720, s. 116-121
  • Tidskriftsartikel (refereegranskat)abstract
    • He-3 was a popular material in neutrons detectors until its availability dropped drastically in 2008. The development of techniques based on alternative convertors is now of high priority for neutron research institutes. Thin films of B-10 or (B4C)-B-10 have been used in gas proportional counters to detect neutrons, but until now, only for small or medium sensitive area. We present here the multi-grid design, introduced at the ILL and developed in collaboration with ESS for LAN (large area neutron) detectors. Typically thirty (B4C)-B-10 films of 1 mu m thickness are used to convert neutrons into ionizing particles which are subsequently detected in a proportional gas counter. The principle and the fabrication of the multi-grid are described and some preliminary results obtained with a prototype of 200 cm x 8 cm are reported; a detection efficiency of 48% has been measured at 2.5 angstrom with a monochromatic neutron beam line, showing the good potential of this new technique. (C) 2013 Elsevier B.V. All rights reserved.
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28.
  • Andersen, Niels S., et al. (författare)
  • Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
  • 2009
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
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29.
  • Auer-Grumbach, Michaela, et al. (författare)
  • Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies
  • 2016
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:3, s. 607-623
  • Tidskriftsartikel (refereegranskat)abstract
    • Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade beta-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.
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30.
  • Cheng, Haynes P. H., et al. (författare)
  • Autofluorescence of pigmented skin lesions using a pulsed UV laser
  • 2010
  • Ingår i: Proceedings of SPIE. - : SPIE. ; 7715, s. 1-77151
  • Konferensbidrag (refereegranskat)abstract
    • We report preliminary clinical results of autofluorescence imaging of malignant and benign skin lesions, using pulsed 355 nm laser excitation with synchronized detection. The novel synchronized detection system allows high signal-tonoise ratio to be achieved in the resulting autofluorescence signal, which may in turn produce high contrast images that improve diagnosis, even in the presence of ambient room light. The synchronized set-up utilizes a compact, diode pumped, pulsed UV laser at 355 nm which is coupled to a CCD camera and a liquid crystal tunable filter. The excitation and image capture is sampled at 5 kHz and the resulting autofluorescence is captured with the liquid crystal filter cycling through seven wavelengths between 420 nm and 580 nm. The clinical study targets pigmented skin lesions and evaluates the prospects of using autofluorescence as a possible means in differentiating malignant and benign skin tumors. Up to now, sixteen patients have participated in the clinical study. The autofluorescence images, averaged over the exposure time of one second, will be presented along with histopathological results. Initial survey of the images show good contrast and diagnostic results show promising agreement based on the histopathological results.
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31.
  • Dencker, Magnus, et al. (författare)
  • Aerobic fitness related to cardiovascular risk factors in young children.
  • 2012
  • Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 1432-1076 .- 0340-6199. ; 171:4, s. 705-710
  • Tidskriftsartikel (refereegranskat)abstract
    • Low aerobic fitness (maximum oxygen uptake (VO(2PEAK))) is predictive for poor health in adults. In a cross-sectional study, we assessed if VO(2PEAK) is related to a composite risk factor score for cardiovascular disease (CVD) in 243 children (136 boys and 107 girls) aged 8 to 11 years. VO(2PEAK) was assessed by indirect calorimetry during a maximal exercise test and scaled by body mass (milliliters per minute per kilogram). Total body fat mass (TBF) and abdominal fat mass (AFM) were measured by Dual-energy X-ray absorptiometry. Total body fat was expressed as a percentage of total body mass (BF%) and body fat distribution as AFM/TBF. Systolic and diastolic blood pressure (SDP and DBP) and resting heart rate (RHR) were measured. The mean artery pressure (MAP) and pulse pressure (PP) were calculated. Echocardiography, 2D-guided M-mode, was performed. Left atrial diameter (LA) was measured and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z scores (value for the individual - mean value for group)/SD were calculated by sex. The sum of z scores for DBP, SDP, PP, MAP, RHR, LVM, LA, RWT, BF%, AFM and AFM/TBF were calculated in boys and girls, separately, and used as composite risk factor score for CVD. Pearson correlation revealed significant associations between VO(2PEAK) and composite risk factor score in both boys (r = -0.48 P < 0.05) and in girls (r = -0.42, P < 0.05). One-way ANOVA analysis indicated significant differences in composite risk factor score between the different quartiles of VO(2PEAK) (P < 0.001); thus, higher VO(2PEAK) was associated with lower composite risk factor score for CVD. In conclusion, low VO(2PEAK) is associated with an elevated composite risk factor score for CVD in both young boys and girls.
  •  
32.
  • Dencker, Magnus, et al. (författare)
  • BMI and objectively measured body fat and body fat distribution in prepubertal children.
  • 2007
  • Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 27:1, s. 12-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Body Mass Index (BMI) is often used as a surrogate estimate of body fat in epidemiological studies. This study explores the association between BMI, body fat and body fat distribution assessed by Dual-Energy X-Ray Absorptiometry (DXA) in younger children. Methods Cross-sectional study of 246 children (138 boys and 108 girls) aged 8-11 years. DXA was used to quantify abdominal fat mass (AFM), total body fat (TBF) and also total body fat as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Results We found close correlations between BMI vs. TBF, BF% and AFM (r = 0.94, r = 0.92 and r = 0.93) for boys and (r = 0.95, r = 0.92 and r = 0.95) for girls, respectively (P < 0.05 for all r-values). However, significantly lower correlation (P < 0.001 for difference between the r-values) existed for body fat distribution (r = 0.64 for boys and 0.73 for girls). Conclusion Percentage body fat, TBF and AFM were all closely associated with BMI, suggesting that BMI serves as a good surrogate marker for obesity in population studies. However, a significantly lower correlation existed for BMI vs. body fat distribution, which may be a limitation when BMI is used to study cardiovascular risk factors in epidemiological studies.
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33.
  • Dencker, Magnus, et al. (författare)
  • Body Fat, Abdominal Fat, and Body Fat Distribution Is Related to Left Atrial Diameter in Young Children.
  • 2012
  • Ingår i: Obesity. - : Wiley. - 1930-739X .- 1930-7381. ; 20, s. 1104-1108
  • Tidskriftsartikel (refereegranskat)abstract
    • In adults, the size of the left atria (LA) has important prognostic information. In obese adults, adolescents and children enlargement of LA have been observed. This has not been investigated on a population-based level in young children. We therefore assessed if total body fat mass (TBF), abdominal fat, and body fat distribution were related to LA diameter. Cross-sectional study of 244 children (boys = 137 and girls n = 107) aged 8-11 years, recruited from an urban population-based cohort. Dual-energy X-ray absorptiometry (DXA) measured total lean body mass, TBF, and abdominal fat mass (AFM). Body fat was also calculated as a percentage of body mass (BF%). Body fat distribution (AFM/TBF) was calculated. Echocardiography was performed with two-dimensional guided M-mode. LA diameter was measured and left ventricular mass (LVM) was calculated. Systolic blood pressure and diastolic blood pressure were measured and maturity assessed according to Tanner. There were significant (P < 0.05) univariate correlations for all children between TBF (r = 0.40), BF% (r = 0.32), AFM (r = 0.41), and AFM/TBF (r = 0.41) vs. LA diameter. Multiple regression analyses with the inclusion of possible confounders such as lean body mass, blood pressure, gender, age, and Tanner stage revealed that TBF, AFM, and AFM/TBF were all independently related to LA diameter. Differences in the different body fat measurements explained 6-9% of the variance in LA size. These results demonstrated that both total body fat, AFM, and body fat distribution are already at a young age negatively and independently associated to LA diameter.
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34.
  • Dencker, Magnus, et al. (författare)
  • Body fat, abdominal fat and body fat distribution related to cardiovascular risk factors in pre-pubertal children.
  • 2012
  • Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 101:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim We analysed whether total body fat, abdominal fat and body fat distribution are associated with higher composite risk factor scores for cardiovascular disease (CVD) in young children. Methods Cross-sectional study of 238 children aged 8-11 years. Total body fat (TBF) and abdominal fat mass (AFM) were measured by DXA. TBF was expressed as a percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VO(2PEAK) ), systolic and diastolic blood pressure (SBP, DBP), and resting heart rate (RHR) were measured. Mean artery pressure (MAP) and pulse pressure (PP) were calculated. Left atrial diameter (LA) was measured, and left ventricular mass (LVM) and relative wall thickness (RWT) were calculated. Z-scores were calculated. Sum of z-scores for SBP, DBP, MAP, PP, RHR, LVM, LA, RWT, and -VO(2PEAK) were calculated in boys and girls, separately, and used as composite risk factor score. Results Pearson correlations between ln BF%, ln AFM and AFM/TBF versus composite risk factor score for boys were r=0.56, r=0.59, and r=0.48, all P<0.001, and for girls r=0.45, r=0.50, and r=0.48, all P<0.001. Conclusion Total body fat, abdominal fat and body fat distribution were all associated with higher composite risk factor scores for CVD in young children. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
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35.
  •  
36.
  • Dencker, Magnus, et al. (författare)
  • Body fat, abdominal fat and body fat distribution related to VO(2PEAK) in young children.
  • 2011
  • Ingår i: International Journal of Pediatric Obesity. - : Informa UK Limited. - 1747-7174 .- 1747-7166. ; 6:2-2, s. 597-602
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Objective. Aerobic fitness, defined as maximum oxygen uptake (VO(2PEAK)), and body fat measurements represent two known risk factors for disease. The purpose of this study was to investigate the relationship between VO(2PEAK) and body fat measurements in young children at a population-based level. Methods. Cross-sectional study of 225 children (128 boys and 97 girls) aged 8-11 years, recruited from a population-based cohort. Total lean body mass (LBM), total fat mass (TBF), and abdominal fat mass (AFM) were measured by dual-energy x-ray absorptiometry. Body fat was also calculated as a percentage of body mass (BF%) and body fat distribution as AFM/TBF. VO(2PEAK) was assessed by indirect calorimetry during maximal exercise test. Results. Significant relationships existed between body fat measurements and VO(2PEAK) in both boys and girls, with Pearson correlation coefficients for absolute values of VO(2PEAK) (0.22-0.36, P< 0.05), and for VO(2PEAK) scaled by body mass (-0.38 - -0.70, P<0.05). No relationships were detected for VO(2PEAK) scaled to LBM (-0.17-0.04, all not significant). Boys and girls in the lowest quartile according to body fat measurements had higher absolute values of VO(2PEAK) and lower values of VO(2PEAK) scaled by body mass, compared with those in the highest quartile. No differences were found for VO(2PEAK) scaled to LBM. Conclusions. Our findings document the coexistence of two known risk factors for disease at a young age and confirms that VO(2PEAK) was scaled to LBM may be a better, body fat independent way of expressing fitness.
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37.
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38.
  •  
39.
  • Dencker, Magnus, et al. (författare)
  • Daily physical activity related to body fat in children aged 8-11 years
  • 2006
  • Ingår i: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 149:1, s. 38-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate the association between objectively measured daily Study design Cross-sectional, observational, study of 248 children aged 7.9 to 11.1 years. Abdominal fat mass and total body fat mass were measured by dual-energy X-ray absorptiometry. Daily physical activity was assessed by accelerometers for 4 days. Results Total body fat expressed as a percentage of body mass was inversely related to minutes of vigorous physical activity per day, for all children r = -0.38 (P < .05). Children, both boys and girls, in the highest quartile of body fat performed on average 12 minutes less vigorous activity per day compared with their counterparts in the lowest quartile. Multiple regression analysis revealed that independent factors for body fat were number of minutes of vigorous activity per day and sex. Conclusion Low physical activity can be a contributing factor in childhood obesity. Only longitudinal studies, however, can give more definitive information about the relation between daily physical activity and obesity.
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40.
  • Dencker, Magnus, et al. (författare)
  • Maximal oxygen uptake versus maximal power output in children
  • 2008
  • Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 26:13, s. 1397-1402
  • Tidskriftsartikel (refereegranskat)abstract
    • Maximal oxygen uptake ([Vdot]O2max) is considered the optimal method to assess aerobic fitness. The measurement of [Vdot]O2max, however, requires special equipment and training. Maximal exercise testing with determination of maximal power output offers a more simple approach. This study explores the relationship between [Vdot]O2max and maximal power output in 247 children (139 boys and 108 girls) aged 7.9-11.1 years. Maximal oxygen uptake was measured by indirect calorimetry during a maximal ergometer exercise test with an initial workload of 30W and 15Wmin-1 increments. Maximal power output was also measured. A sample (n=124) was used to calculate reference equations, which were then validated using another sample (n=123). The linear reference equation for both sexes combined was: [Vdot]O2max (mlmin-1)=96 + 10.6maximal power + 3.5body mass. Using this reference equation, estimated [Vdot]O2max per unit of body mass (mlmin-1kg-1) calculated from maximal power correlated closely with the direct measurement of [Vdot]O2max (r=0.91, P0.001). Bland-Altman analysis gave a mean limits of agreement of 0.22.9 (mlmin-1kg-1) (1s). Our results suggest that maximal power output serves as a good surrogate measurement for [Vdot]O2max in population studies of children aged 8-11 years.
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41.
  • Dencker, Magnus, et al. (författare)
  • Objectively measured daily physical activity related to cardiac size in young children.
  • 2009
  • Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 1600-0838 .- 0905-7188. ; Aug 5, s. 664-668
  • Tidskriftsartikel (refereegranskat)abstract
    • Training studies in children have suggested that endurance training can give enlargement of cardiac dimensions. This relationship has not been studied on a population-based level in young children with objective methods. A cross-sectional study was made of 248 children (140 boys and 108 girls), aged 8-11 years, from a population-based cohort. Left ventricular end-diastolic diameter (LVDD) and left atrial end-systolic diameter (LA) were measured with echocardiography and indexed for body surface area (BSA). Physical activity was assessed by accelerometry, and the duration of vigorous physical activity per day (VPA) was calculated. Acceptable accelerometer and echocardiography measurements were obtained in 228 children (boys=127, girls=101). Univariate correlations between VPA and LVDD were indexed for BSA in boys (r=0.27, P<0.05) and in girls (r=0.10, NS). Multiple regression analysis showed that independent factors for LVDD, indexed for BSA for boys, were age and VPA. LA indexed for BSA was not related to physical activity variables in either gender. No clear relationship exists between cardiac size and daily physical activity in children aged 8-11 years. This suggests that significant cardiac remodelling due to volume exposure secondary to a high amount of physical activity begins later in life.
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42.
  • Fronczek, Jakub, et al. (författare)
  • Short-term mortality or patients >= 80 years old admitted to European intensive care units: an international observational study
  • 2022
  • Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 129:1, s. 58-66
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Limited evidence suggests variation in mortality of older critically ill adults across Europe. We aimed to investigate regional differences in mortality among very old ICU patients. Methods: Multilevel analysis of two international prospective cohort studies. We included patients >= 80 yr old from 322 ICUs located in 16 European countries. The primary outcome was mortality within 30 days from admission to the ICU. Results are presented as n (%) with 95% confidence intervals and odds ratios (ORs). Results: Of 8457 patients, 2944 (36.9% [35.9-38.0%]) died within 30 days. Crude mortality rates varied widely between participating countries (from 10.1% [6.4-15.6%] to 45.1% [41.1-49.2%] in the ICU and from 21.3% [16.3-28.9%] to 55.3% [51.1-59.5%] within 30 days). After adjustment for confounding variables, the variation in 30-day mortality between countries was substantially smaller than between ICUs (median OR 1.14 vs 1.58). Healthcare expenditure per capita (OR=0.84 per $1000 [0.75-0.94]) and social health insurance framework (OR=1.43 [1.01-2.01]) were associated with ICU mortality, but the direction and magnitude of these relationships was uncertain in 30-day follow-up. Volume of admissions was associated with lower mortality both in the ICU (OR=0.81 per 1000 annual ICU admissions [0.71-0.94]) and in 30-day follow-up (OR=0.86 [0.76-0.97]). Conclusion: The apparent variation in short-term mortality rates of older adults hospitalised in ICUs across Europe can be largely attributed to differences in the clinical profile of patients admitted. The volume-outcome relationship identified in this population requires further investigation.
  •  
43.
  • Geisler, Christian H., et al. (författare)
  • Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue : a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group
  • 2008
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 112:7, s. 2687-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
  •  
44.
  • Geisler, Christian H., et al. (författare)
  • Nordic MCL2 trial update : six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC plus autologous stem-cell support: still very long survival but late relapses do occur
  • 2012
  • Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 158:3, s. 355-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early based on the median observation time of 4 years results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6.5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7.4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL.
  •  
45.
  • Goncalves, Nadia P., et al. (författare)
  • Peripheral Nerve Regeneration Is Independent From Schwann Cell p75(NTR) Expression
  • 2019
  • Ingår i: Frontiers in Cellular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5102. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Schwann cell reprogramming and differentiation are crucial prerequisites for neuronal regeneration and re-myelination to occur following injury to peripheral nerves. The neurotrophin receptor p75(NTR) has been identified as a positive modulator for Schwann cell myelination during development and implicated in promoting nerve regeneration after injury. However, most studies base this conclusion on results obtained from complete p75(NTR) knockout mouse models and cannot dissect the specific role of p75(NTR) expressed by Schwann cells. In this present study, a conditional knockout model selectively deleting p75(NTR) expression in Schwann cells was generated, where p75(NTR) expression is replaced with that of an mCherry reporter. Silencing of Schwann cell p75(NTR) expression was confirmed in the sciatic nerve in vivo and in vitro, without altering axonal expression of p75(NTR). No difference in sciatic nerve myelination during development or following sciatic nerve crush injury was observed, as determined by quantification of both myelinated and unmyelinated nerve fiber densities, myelinated axonal diameter and myelin thickness. However, the absence of Schwann cell p75(NTR) reduced motor nerve conduction velocity after crush injury. Our data indicate that the absence of Schwann cell p75(NTR) expression in vivo is not critical for axonal regrowth or remyelination following sciatic nerve crush injury, but does play a key role in functional recovery. Overall, this represents the first step in redefining the role of p75(NTR) in the peripheral nervous system, suggesting that the Schwann cell-axon unit functions as a syncytium, with the previous published involvement of p75(NTR) in remyelination most likely depending on axonal/neuronal p75(NTR) and/or mutual glial-axonal interactions.
  •  
46.
  • Gustafsen, Camilla, et al. (författare)
  • Heparan sulfate proteoglycans present PCSK9 to the LDL receptor
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats. Accordingly, heparan sulfate mimetics and monoclonal antibodies directed against the heparan sulfate-binding site are potent PCSK9 inhibitors. We propose that heparan sulfate proteoglycans lining the hepatocyte surface capture PCSK9 and facilitates subsequent PCSK9: LDLR complex formation. Our findings provide new insights into LDL biology and show that targeting PCSK9 using heparan sulfate mimetics is a potential therapeutic strategy in coronary artery disease.
  •  
47.
  • Hansen, Benni W., et al. (författare)
  • In situ and experimental evidence for effects of elevated pH on protistan and metazoan grazers
  • 2019
  • Ingår i: Journal of Plankton Research. - : Oxford University Press (OUP). - 0142-7873 .- 1464-3774. ; 41:3, s. 257-271
  • Tidskriftsartikel (refereegranskat)abstract
    • Plankton succession was studied in a hyper-eutrophic stratified estuary, Mariager Fjord, Denmark. Above the pycnocline (15 m) pH increased from 8.5 to 9.2 and the oxygen increased to super saturation after 5 d of sunny weather due to high primary production. The protistan grazers were dominated by heterotrophic dinoflagellates and mixotrophic and heterotrophic ciliates. Metazooplankton was dominated by meroplankton, rotifers and the copepod, Acartia tonsa, all with a relatively low biomass. Cirriped nauplii occupied the upper strata while polychaete larvae populated the whole water column. Bivalve larvae occurred occasionally above the pycnocline even at very high pH. In pH challenge experiments, the mixotrophic ciliate Mesodinium rubrum was the least pH tolerant species, followed by Strombidium spp., which did not cope well with seawater pH > 8.5. Some heterotrophic dinoflagellates were more tolerant with net growth at pH > 9. The predominant rotifer Synchaeta sp. tolerated up to pH 9.5 and the copepod survived pH 10 but stopped producing eggs at pH 9.5 with unaffected egg hatching success. The polychaete and cirriped larvae tolerated pH 9.5, but bivalve larvae showed decreased survival already at pH 8.5. In situ distribution patterns and pH challenge experiments suggest that pH indeed contribute to structuring zooplankton distribution.
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48.
  • Hedengran, Katrine K., et al. (författare)
  • Environmental tobacco smoke exposure during pregnancy has limited effect on infant birthweight and umbilical vein endothelial nitric oxide synthase
  • 2018
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 97:11, s. 1309-1316
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Women who smoke, deliver significantly smaller infants. These infants have reduced levels of the vasodilator endothelial nitric oxide synthase (eNOS) levels in the umbilical vessels, which may reduce fetal growth. Serum cotinine, the degradation product of nicotine, can be used to determine the level of tobacco exposure. Newborns of environmental smokers are suggested to be smaller and shorter in weight, length, and head circumference. eNOS levels have not yet been studied in these infants. We here investigated the existence of a relation between maternal environmental tobacco smoke exposure, eNOS activity, concentration, and birthweight. Material and methods: We included 263 healthy singleton pregnancies categorized into three groups according to measured cotinine levels: 175 nonsmokers, 38 smokers, and 50 environmental smokers. Cotinine was quantified by mass spectrometry with a detection limit of.2 ng/mL; eNOS activity and concentration were measured in endothelial cells (ECs) of the umbilical vein. Results: Infants born to environmental smokers had similar weights to infants born to nonsmokers (47 g heavier, P =.48). Cotinine concentrations were.06/.09/.12 ng/mL (quartiles) in infants born to nonsmokers,.27/.37/.81 ng/mL in infants born to women exposed to environmental tobacco smoke, and 43.0/63.8/108.1 ng/mL in infants born to smokers. The eNOS concentration was 1.65 ±.92 ng/106 ECs (mean ± SD) in nonsmokers and 1.71 ± 1.00 ng/106 ECs in environmental smokers. The eNOS activity was 52.0 ± 20.6 pmol l-citrulline/min/106 ECs in nonsmokers and 48.7 ± 19.8 pmol l-citrulline/min/106 ECs in environmental smokers. Conclusions: Infants born to environmental smokers, as judged by umbilical serum cotinine levels close to.2 ng/mL, are not associated with lower birthweight or reduced eNOS activity, or concentration in the fetal vascular bed.
  •  
49.
  • Hidalgo Migueles, Jairo Hidalgo, et al. (författare)
  • GRANADA consensus on analytical approaches to assess associations with accelerometer-determined physical behaviours (physical activity, sedentary behaviour and sleep) in epidemiological studies
  • 2022
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 56:7, s. 376-384
  • Tidskriftsartikel (refereegranskat)abstract
    • The inter-relationship between physical activity, sedentary behaviour and sleep (collectively defined as physical behaviours) is of interest to researchers from different fields. Each of these physical behaviours has been investigated in epidemiological studies, yet their codependency and interactions need to be further explored and accounted for in data analysis. Modern accelerometers capture continuous movement through the day, which presents the challenge of how to best use the richness of these data. In recent years, analytical approaches first applied in other scientific fields have been applied to physical behaviour epidemiology (eg, isotemporal substitution models, compositional data analysis, multivariate pattern analysis, functional data analysis and machine learning). A comprehensive description, discussion, and consensus on the strengths and limitations of these analytical approaches will help researchers decide which approach to use in different situations. In this context, a scientific workshop and meeting were held in Granada to discuss: (1) analytical approaches currently used in the scientific literature on physical behaviour, highlighting strengths and limitations, providing practical recommendations on their use and including a decision tree for assisting researchers decision-making; and (2) current gaps and future research directions around the analysis and use of accelerometer data. Advances in analytical approaches to accelerometer-determined physical behaviours in epidemiological studies are expected to influence the interpretation of current and future evidence, and ultimately impact on future physical behaviour guidelines.
  •  
50.
  • Jensen, Pernille Linnert, et al. (författare)
  • Proteomic Analysis of Human Blastocoel Fluid and Blastocyst Cells
  • 2013
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 22:7, s. 1126-1135
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the blastocyst and can differentiate into any cell type in the human body. These cells hold a great potential for regenerative medicine, but in order to obtain enough cells needed for medical treatment, culture is required on a large scale. In the undifferentiated state, hESCs appear to possess an unlimited potential for proliferation but optimal, defined and safe culture conditions remains a challenge. The aim of the present study was to identify proteins in the natural environment of undifferentiated hESCs, namely the blastocoel fluid, which is in contact with all the cells in the blastocyst, including hESCs. Fifty-three surplus human blastocysts were donated after informed consent and blastocoel fluid was isolated by micromanipulation. Using highly sensitive nano high pressure liquid chromatography tandem mass spectrometry, 286 proteins were identified in the blastocoel fluid and 1307 proteins in the corresponding cells of the blastocyst. Forty-two were previously uncharacterized proteins - eight of these originated from the blastocoel fluid. Furthermore, several heat shock proteins (Hsp27, Hsp60, Hsc70 and Hsp90) were identified in blastocoel fluid together with zona pellucida proteins (ZP2-4), Vitamin D binding protein and Retinol binding protein. Proteins that regulate ciliary assembly and function were also identified, including Bardet-biedl syndrome protein 7. This study has identified numerous proteins which cells from the ICM of the human blastocyst are exposed to via the blastocoel fluid. These results can be an inspiration for the development of improved culture conditions for hESCs.
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