| 1. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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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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| 2. |
- Einarsson, Snorri, 1973, et al.
(författare)
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Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.
- 2017
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 32:8, s. 1621-1630
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Tidskriftsartikel (refereegranskat)abstract
- Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women?An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF.Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women.A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included.Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only.In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found.The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2.The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results.The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose.ClinicalTrials.gov number, NCT01566929.23-03-2012.05-10-2010.
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| 3. |
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| 4. |
- Lindberg, Anne, 1957-
(författare)
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Chronic obstructive pulmonary disease (COPD) : prevalence, incidence, decline in lung function and risk factors
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Obstructive Lung Disease in Northern Sweden (OLIN) Studies started in 1985 as an epidemiological project with the aim to detect preventable risk factors for obstructive lung diseases and allergy. In recent years there has been a focus also on obstructive sleep apnoea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) besides asthma and allergy. The aim of this thesis was to estimate the prevalence and incidence of COPD, risk factors for COPD, and decline in lung function in relation to COPD.The OLIN cohort I (cI) was recruited in 1985/86 and consisted of all 6610 subjects born 1919-20, 1934-35 and 1949-50 in eight geographical areas of Norrbotten. A postal questionnaire survey was performed in 1985/86, 1992 and in 1996. All subjects reporting respiratory symptoms at the questionnaire in 1985/86 were invited to examination in 1986, 1996 and 2002-03. A random sample of 1500 subjects from the participants at the 1996 postal questionnaire survey was invited to examination in 1996 and 2003. The participation rate has been high, ≥85%. The OLIN cohort III (cIII) was recruited in 1992, a postal questionnaire was sent to a random sample of 5681 subjects aged 20-69 years. In 1994/95 a random sample of 970 subjects were invited to examination of whom 666 participated.The prevalence of COPD in the general population sample (cIII) in ages <45 was 4.1%, 11.6%, 9.1%, and 5.1% according to the criteria of BTS1 , ERS2 , GOLD3 , and ATS4 respectively. The corresponding figures in ages ≥45 were 9.7%, 15.4%, 17.1%, and 16.5% respectively. In the age-stratified general population sample (>45 y, cI), the prevalence was 8.1% and 14.3% according to the BTS and GOLD criteria. The prevalence was strongly associated with higher age and smoking but not gender. The prevalence among smokers 76-77 years old was 45% and 50% (BTS and GOLD criteria). A majority of subjects with COPD had respiratory symptoms (in prevalent BTS 94%), most commonly cough and sputum production. Nearly a half of the subjects with COPD had contacted health care due to respiratory complaints other than common colds, but only a minority reported a physician diagnosis relevant for COPD (16% of prevalent COPD according to BTS in cIII, 31% in cI). The 10-year cumulative incidence of COPD (1986-1996) was estimated at 8.2% (BTS) and 13.5% (GOLD) in the symptomatics of cI, associated with higher age and smoking but not gender. Persistent smoking, male gender and reported chronic productive cough were associated with a faster decline in FEV1. Among incident cases of COPD a large proportion (23% of incident BTS) had a rapid decline in FEV1, >90 ml/year, corresponding to a decrease of 28 percent-units of normal value during ten years.The 7-year cumulative incidence of COPD in the random sample of cI (1996-2003) was estimated at 4.9% and 11.0% (NICE guidelines5 and GOLD) and associated with smoking but not gender. The incidence according to GOLD, but not NICE, was associated with increasing age. In multi-variate analysis most respiratory symptoms were markers of increased risk for developing COPD.In conclusion, the prevalence and the incidence of COPD were associated with age and smoking and affected by the use of different spirometric criteria. Respiratory symptoms marked an increased risk for developing COPD. A high proportion of subjects developing COPD had a rapid decline in lung function. Further, there was a substantial underdiagnosis of COPD.1 British Thoracic Society: FEV1/VC<0.70 & FEV1<80%predicted (pred), 2 European Respiratory Society: FEV1/VC<88%pred in men, <89%pred in women, 3 Global initiative for Chronic Obstructive Lung Disease:FEV1/FVC<0.70, 4 American Thoracic Society: FEV1/FVC<0.75 + symptoms or physician diagnosis, 5 The British National Institute for Clinical Excellence: FEV1/FVC<0.70 & FEV1<80%pred.
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| 5. |
- Lindberg, Anne, et al.
(författare)
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Decline in FEV1 in relation to incident chronic obstructive pulmonary disease in a cohort with respiratory symptoms.
- 2007
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Ingår i: COPD. - : Informa UK Limited. - 1541-2555. ; 4:1, s. 5-13
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Tidskriftsartikel (refereegranskat)abstract
- Data on the relationship between decline in lung function and development of COPD are sparse. We assessed the decline in FEV1 during 10 years among subjects with respiratory symptoms by two different methods and evaluated risk factors for decline and its relation to incident Chronic Obstructive Pulmonary Disease, COPD. A cross-sectional postal questionnaire was in 1986 sent to 6610 subjects of three age strata. All subjects reporting respiratory symptoms were invited to a structured interview and spirometry. A follow-up survey was performed 10 years later, and totally 1109 subjects performed spirometry in both 1986 and 1996. COPD was defined according to the ATS/ERS standards (FEV1/FVC < or =0.70). The decline in FEV1 was 39 ml/year in men vs. 28 ml/year in women, p = < 0.001 (-1.53 vs. -0.12 change in percent of predicted normal value over 10 years (pp), p = 0.023), among smokers 39 vs. non-smokers 28 ml/year, p < 0.001 (-3.30 vs. 0.69 pp, p < 0.001), in subjects with chronic productive cough 36 vs. not 32 ml/year, p = 0.044 (-2.00 vs. -0.02 pp, p = 0.002). Incident cases of moderate COPD (n = 83) had a decline of 62 ml/year (-12.6 pp) and 22.9% of them had a decline > 90 ml/year (-27.8 pp over 10 years). Gender-specific analysis revealed that smoking was a stronger risk factor in women than in men, while higher age was a significant risk factor in men only. In conclusion, decline in FEV1 was associated with age, smoking, and chronic productive cough, but the risk factor pattern was gender-dependent. Among incident cases of COPD the decline was steeper and close to a quarter had a rapid decline.
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| 6. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 7. |
- Ludvigsson, Johnny, et al.
(författare)
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GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 366:5, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.
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| 8. |
- Lugar, Marija, et al.
(författare)
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SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood
- 2023
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Ingår i: JAMA. - 0098-7484. ; 330:12
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends.OBJECTIVE: To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.DESIGN, SETTING, AND PARTICIPANTS: Between February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022.EXPOSURE: SARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022.MAIN OUTCOMES AND MEASURES: The development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed.RESULTS: Consent was obtained for 885 (441 girls) children who were included in follow-up antibody measurements from age 6 months. SARS-CoV-2 antibodies developed in 170 children at a median age of 18 months (range, 6-25 months). Islet autoantibodies developed in 60 children. Six of these children tested positive for islet autoantibodies at the same time as they tested positive for SARS-CoV-2 antibodies and 6 at the visit after having tested positive for SARS-CoV-2 antibodies. The sex-, age-, and country-adjusted hazard ratio for developing islet autoantibodies when the children tested positive for SARS-CoV-2 antibodies was 3.5 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies (P = .02). Islet autoantibody risk in children with SARS-CoV-2 antibodies was associated with younger age (<18 months) of SARS-CoV-2 antibody development (HR, 5.3; 95% CI, 1.5-18.3; P = .009).CONCLUSION AND RELEVANCE: In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.
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| 9. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 10. |
- Molia, Anne, et al.
(författare)
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Elaphomyces section Elaphomyces (Eurotiales, Ascomycota) — taxonomy and phylogeny of North European taxa, with the introduction of three new species
- 2020
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Ingår i: Fungal Systematics and Evolution. - : Westerdijk Fungal Biodiversity Institute. - 2589-3823 .- 2589-3831. ; 5, s. 283-300
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Tidskriftsartikel (refereegranskat)abstract
- The North European species of Elaphomyces section Elaphomyces (Eurotiales, Pezizomycotina) are studied. Three new species, E. citrinopapillatus, E. pusillus, and E. roseoviolaceus are introduced and verified by morphology and sequence data from ITS, nuclear LSU, mitochondrial SSU, and β-tubulin. A lectotype for Elaphomyces granulatus is selected. Elaphomyces granulatus and E. muricatus are epitypified with sequenced material from the Femsjö region in South Sweden. Elaphomyces striatosporus is epitypified with sequenced material from the vicinity of the type locality in Norway. A key to all species of Elaphomyces occurring in Denmark, Norway, and Sweden is provided.
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