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- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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- Jersin, R. A., et al.
(author)
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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
- 2021
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
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Journal article (peer-reviewed)abstract
- Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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- Western, Benedikte, et al.
(author)
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Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study
- 2024
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In: Scandinavian Journal of Medicine and Science in Sports. - Chichester, West Sussex : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 34:2, s. 1-10
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Journal article (peer-reviewed)abstract
- Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects. © 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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- Kurilshikov, Alexander, et al.
(author)
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Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
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Journal article (peer-reviewed)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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- Stritzinger, M. D., et al.
(author)
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Optical and near-IR observations of the faint and fast 2008ha-like supernova 2010ae
- 2014
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 561, s. A146-
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Journal article (peer-reviewed)abstract
- A comprehensive set of optical and near-infrared (NIR) photometry and spectroscopy is presented for the faint and fast 2008ha-like supernova (SN) 2010ae. Contingent on the adopted value of host extinction, SN 2010ae reached a peak brightness of -13.8 > M-V > -15.3 mag, while modeling of the UVOIR light curve suggests it produced 0.003-0.007 M-circle dot of Ni-56, ejected 0.30-0.60 M-circle dot of material, and had an explosion energy of 0.04-0.30 x 10(51) erg. The values of these explosion parameters are similar to the peculiar SN 2008ha -for which we also present previously unpublished early phase optical and NIR light curves - and places these two transients at the faint end of the 2002cx-like SN population. Detailed inspection of the post-maximum NIR spectroscopic sequence indicates the presence of a multitude of spectral features, which are identified through SYNAPPS modeling to be mainly attributed to Co II. Comparison with a collection of published and unpublished NIR spectra of other 2002cx-like SNe, reveals that a Co II footprint is ubiquitous to this subclass of transients, providing a link to Type Ia SNe. A visual-wavelength spectrum of SN 2010ae obtained at +252 days past maximum shows a striking resemblance to a similar epoch spectrum of SN 2002cx. However, subtle differences in the strength and ratio of calcium emission features, as well as diversity among similar epoch spectra of other 2002cx-like SNe indicates a range of physical conditions of the ejecta, highlighting the heterogeneous nature of this peculiar class of transients.
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- Siersma, V., et al.
(author)
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Importance of factors determining the low health-related quality of life in people presenting with a diabetic foot ulcer: the Eurodialestudy
- 2013
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In: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 30:11, s. 1382-1387
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Journal article (peer-reviewed)abstract
- AimTo identify the factors responsible for the low health-related quality of life associated with foot ulcers and the relative importance of these factors. MethodsA total of 1232 patients with a new foot ulcer, who presented at one of the 14 centres in 10 European countries participating in the Eurodiale study, were included in this cross-sectional study. Patient and ulcer characteristics were obtained as well as results from the Euro-Qol-5D questionnaire, a health-related quality of life instrument with five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). To analyse the relative importance of comorbidities and ulcer- and patient-related factors for health-related quality of life, linear regression models were used to calculate the relative contributions of each factor to the fit (R-2) of the model. ResultsPatients reported poor overall health-related quality of life, with problems primarily in the mobility and pain/discomfort domains. Among the comorbidities, the inability to stand or walk without help was the most important determinant of decreased health-related quality of life in all five domains. Among ulcer-related factors, ulcer size, limb-threatening ischaemia and elevated C-reactive protein concentration also had high importance in all domains. The clinical diagnosis of infection, peripheral arterial disease and polyneuropathy were only important in the pain/discomfort domain. ConclusionsThe factors that determine health-related quality of life are diverse and to an extent not disease-specific. To improve health-related quality of life, treatment should not only be focused on ulcer healing but a multifactorial approach by a specialized multidisciplinary team is also important. What's new? The inability to stand or walk without help is the most important determinant of poor health-related quality of life. Other factors with high importance are ulcer size, elevated C-reactive protein concentration and limb-threatening ischaemia. To improve health-related quality of life, treatment should not only be focused on ulcer healing but a multifactorial approach by a specialized multidisciplinary team is also important.
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- Thorsen, Steffen U, et al.
(author)
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Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload : Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study
- 2023
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:5, s. 1014-1018
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.
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- Weeland, CJ, et al.
(author)
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The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder
- 2022
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 70-
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Journal article (peer-reviewed)abstract
- Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = −0.15 to −0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.
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- Fiessinger, J. N., et al.
(author)
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Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial
- 2005
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In: Jama. - 1538-3598. ; 293:6, s. 681-9
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Journal article (peer-reviewed)abstract
- CONTEXT: Ximelagatran, an oral direct thrombin inhibitor with a rapid onset of action and predictable antithrombotic effect, has the potential to be a simple therapeutic alternative to current standard treatment of acute venous thromboembolism. OBJECTIVE: To compare the efficacy and safety of ximelagatran with standard enoxaparin/warfarin treatment for the prevention of recurrent venous thromboembolism. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, noninferiority trial (Thrombin Inhibitor in Venous Thromboembolism [THRIVE] Treatment Study) of 2489 patients with acute deep vein thrombosis, of whom approximately one third had concomitant pulmonary embolism. The study was conducted at 279 centers in 28 countries from September 2000 through December 2002. INTERVENTIONS: Patients were randomized to receive 6 months of treatment with either oral ximelagatran, 36 mg twice daily, or subcutaneous enoxaparin, 1 mg/kg twice daily, for 5 to 20 days followed by warfarin adjusted to maintain an international normalized ratio of 2.0 to 3.0. MAIN OUTCOME MEASURES: Recurrent venous thromboembolism, bleeding, and mortality. RESULTS: Venous thromboembolism recurred in 26 of the 1240 patients assigned to receive ximelagatran (estimated cumulative risk, 2.1%) and in 24 of the 1249 patients assigned to receive enoxaparin/warfarin (2.0%). The absolute difference between ximelagatran and enoxaparin/warfarin was 0.2% (95% confidence interval [CI], -1.0% to 1.3%). This met the prespecified criterion for noninferiority. Corresponding values for major bleeding were 1.3% and 2.2% (difference, -1.0%; 95% CI, -2.1% to 0.1%), and for mortality were 2.3% and 3.4% (difference, -1.1%; 95% CI, -2.4% to 0.2%). Alanine aminotransferase levels increased to more than 3 times the upper limit of normal in 119 patients (9.6%) and 25 patients (2.0%) receiving ximelagatran and enoxaparin/warfarin, respectively. Increased enzyme levels were mainly asymptomatic. Retrospective analysis of locally reported adverse events showed a higher rate of serious coronary events with ximelagatran (10/1240 patients) compared with enoxaparin/warfarin (1/1249 patients). CONCLUSIONS: Oral ximelagatran administered in a fixed dose without coagulation monitoring, was as effective as enoxaparin/warfarin for treatment of deep vein thrombosis with or without pulmonary embolism and showed similar, low rates of bleeding. Increased levels of liver enzymes in 9.6% of ximelagatran-treated patients require regular monitoring; the mechanism requires further evaluation. Prospective assessment of coronary events in future studies is warranted.
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- Guaita, Lucia, et al.
(author)
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The Lyman alpha reference sample IV. Morphology at low and high redshift
- 2015
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576
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Journal article (peer-reviewed)abstract
- Context. The transport of Ly alpha photons in galaxies is a complex process and the conditions under which Ly alpha photons manage to escape from certain galaxies is still under investigation. The Lyman alpha reference sample (LARS) is a sample of 14 local star-forming galaxies, designed to study Ly alpha in detail and relate it to rest-frame UV and optical emission. Aims. With the aim of identifying rest-frame UV and optical properties, which are typical of Ly alpha emitters (LAEs, galaxies with EW(Ly alpha) > 20 angstrom) at both low and high redshift, we investigated the morphological properties of the LARS galaxies, in particular the ones that exhibit intense Ly alpha radiation. Methods. We measured sizes and morphological parameters in the continuum, Ly alpha, and Ha images. We studied morphology by using the Gini coefficient vs. M20 and asymmetry vs. concentration diagrams. We then simulated LARS galaxies at z similar to 2 and 5.7, performing the same morphological measurements. We also investigated the detectability of LARS galaxies in current deep field observations. The subsample of LAEs within LARS (LARS-LAEs) was stacked to provide a comparison to stacking studies performed at high redshift. Results. LARS galaxies have continuum size, stellar mass, and rest-frame absolute magnitude typical of Lyman break analogues in the local Universe and also similar to 2 < z < 3 star-forming galaxies and massive LAEs. LARS optical morphology is consistent with the one of merging systems, and irregular or starburst galaxies. For the first time we quantify the morphology in Ly alpha images: even if a variety of intrinsic conditions of the interstellar medium can favour the escape of Ly alpha photons, LARS-LAEs appear small in the continuum, and their Ly alpha is compact. LARS galaxies tend to be more extended in Ly alpha than in the rest-frame UV. It means that Ly alpha photons escape by forming haloes around HII regions of LARS galaxies. Conclusions. The stack of LARS-LAE Ly alpha images is peaked in the centre, indicating that the conditions, which make a galaxy an LAE, tend to produce a concentrated surface brightness profile. On the other hand, the stack of all LARS galaxies is shallower and more extended. This can be caused by the variety of dust and HI amount and distribution, which produces a more complex, patchy, and extended profile, like the one observed for Lyman break galaxies that can contribute to the stack. We cannot identify a single morphological property that controls whether a galaxy emits a net positive Ly alpha flux. However, the LARS-LAEs have continuum properties consistent with merging systems.
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- Herenz, Edmund Christian, et al.
(author)
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The Lyman alpha reference sample VII. Spatially resolved H alpha kinematics
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 587
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Journal article (peer-reviewed)abstract
- We present integral field spectroscopic observations with the Potsdam Multi-Aperture Spectrophotometer of all 14 galaxies in the z similar to 0.1 Lyman Alpha Reference Sample (LARS). We produce 2D line-of-sight velocity maps and velocity dispersion maps from the Balmer alpha (H alpha) emission in our data cubes. These maps trace the spectral and spatial properties of the LARS galaxies' intrinsic Ly alpha radiation field. We show our kinematic maps that are spatially registered onto the Hubble Space Telescope H alpha and Lyman alpha (Ly alpha) images. We can conjecture a causal connection between spatially resolved H alpha kinematics and Ly alpha photometry for individual galaxies, however, no general trend can be established for the whole sample. Furthermore, we compute the intrinsic velocity dispersion sigma(0), the shearing velocity v(shear), and the v(shear)/sigma(0) ratio from our kinematic maps. In general LARS galaxies are characterised by high intrinsic velocity dispersions (54 km s(-1) median) and low shearing velocities (65 km s(-1) median). The v(shear/sigma 0) values range from 0.5 to 3.2 with an average of 1.5. It is noteworthy that five galaxies of the sample are dispersion-dominated systems with v(shear)/sigma(0) < 1, and are thus kinematically similar to turbulent star-forming galaxies seen at high redshift. When linking our kinematical statistics to the global LARS Ly alpha properties, we find that dispersion-dominated systems show higher Ly alpha equivalent widths and higher Ly alpha escape fractions than systems with v(shear)/sigma(0) > 1. Our result indicates that turbulence in actively star-forming systems is causally connected to interstellar medium conditions that favour an escape of Ly alpha radiation.
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- Komarova, Lena, et al.
(author)
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Haro 11 : The Spatially Resolved Lyman Continuum Sources
- 2024
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 967:2
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Journal article (peer-reviewed)abstract
- As the nearest confirmed Lyman continuum (LyC) emitter, Haro 11 is an exceptional laboratory for studying LyC escape processes crucial to cosmic reionization. Our new Hubble Space Telescope/Cosmic Origins Spectrograph G130M/1055 observations of its three star-forming knots now reveal that the observed LyC originates in Knots B and C, with 903–912 Å luminosities of 1.9 ± 1.5 × 1040 erg s−1 and 0.9 ± 0.7 × 1040 erg s−1, respectively. We derive local escape fractions fesc,912 = 3.4% ± 2.9% and 5.1% ± 4.3% for Knots B and C, respectively. Our Starburst99 modeling shows dominant populations on the order of ∼1–4 Myr and 1–2 × 107M⊙ in each knot, with the youngest population in Knot B. Thus, the knot with the strongest LyC detection has the highest LyC production. However, LyC escape is likely less efficient in Knot B than in Knot C due to higher neutral gas covering. Our results therefore stress the importance of the intrinsic ionizing luminosity, and not just the escape fraction, for LyC detection. Similarly, the Lyα escape fraction does not consistently correlate with LyC flux, nor do narrow Lyα red peaks. High observed Lyα luminosity and low Lyα peak velocity separation, however, do correlate with higher LyC escape. Another insight comes from the undetected Knot A, which drives the Green Pea properties of Haro 11. Its density-bounded conditions suggest highly anisotropic LyC escape. Finally, both of the LyC-leaking Knots, B and C, host ultraluminous X-ray sources (ULXs). While stars strongly dominate over the ULXs in LyC emission, this intriguing coincidence underscores the importance of unveiling the role of accretors in LyC escape and reionization.
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