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1.	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.
2.	Aslam, Tayyba N., et al. (författare) A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure 2023 Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:10, s. 1383-1394 Tidskriftsartikel (refereegranskat)abstract BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
3.	Granholm, Anders, et al. (författare) Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial 2022 Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48:1, s. 45-55 Tidskriftsartikel (refereegranskat)abstract Purpose We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. Methods We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. Results The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. Conclusion We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.
4.	Granholm, Anders, et al. (författare) Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis 2021 Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:5, s. 702-710 Tidskriftsartikel (refereegranskat)abstract Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
5.	Granholm, Anders, et al. (författare) Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia 2022 Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 580-589 Tidskriftsartikel (refereegranskat)abstract Purpose We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). Conclusion Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.
6.	Munch, Marie Warrer, et al. (författare) Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial : Protocol and statistical analysis plan 2021 Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:6, s. 834-845 Tidskriftsartikel (refereegranskat)abstract Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. Methods The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. Discussion The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.
7.	Bach, Anders, et al. (författare) A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage 2012 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:9, s. 3317-3322 Tidskriftsartikel (refereegranskat)abstract Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.
8.	Guillemain, Matthieu, et al. (författare) Effects of climate change on European ducks : what do we know and what do we need to know? 2013 Ingår i: Wildlife Biology. - : Nordic Council of Wildlife Research. - 0909-6396 .- 1903-220X. ; 19:4, s. 404-419 Tidskriftsartikel (refereegranskat)abstract The consequences of climate change for bird populations have received much attention in recent decades, especially amongst cavity-nesting songbirds, yet little has been written on ducks (Anatidae) despite these being major elements of wetland diversity and important quarry species. This paper reviews the major known consequences of climate change for birds in general, and relates these to the limited information available specifically for ducks. Climate change can influence migration distance and phenology, potentially affecting patterns of mortality, as well as distribution and reproductive success in ducks. Studies addressing effects of climate change are, however, restricted to very few duck species, including mallardAnas platyrhynchos and common eider Somateria mollissima. Shifts in winter duck distributions have been observed, whereas the mismatch hypothesis (mistiming between the periods of peak energy requirements for young and the peak of seasonal food availability) has received limited support with regard to ducks. We propose a range of monitoring initiatives, including population surveys, breeding success monitoring schemes and individual duck marking, which should later be integrated through population modelling and adaptive management to fill these gaps.
9.	Krag, Mette, et al. (författare) Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients 2015 Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:5, s. 833-845 Tidskriftsartikel (refereegranskat)abstract To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients. We included adults without GI bleeding who were acutely admitted to the intensive care unit (ICU) during a 7-day period. The primary outcome was clinically important GI bleeding in ICU, and the analyses included estimations of baseline risk factors and potential associations with 90-day mortality. A total of 1,034 patients in 97 ICUs in 11 countries were included. Clinically important GI bleeding occurred in 2.6 % (95 % confidence interval 1.6-3.6 %) of patients. The following variables at ICU admission were independently associated with clinically important GI bleeding: three or more co-existing diseases (odds ratio 8.9, 2.7-28.8), co-existing liver disease (7.6, 3.3-17.6), use of renal replacement therapy (6.9, 2.7-17.5), co-existing coagulopathy (5.2, 2.3-11.8), acute coagulopathy (4.2, 1.7-10.2), use of acid suppressants (3.6, 1.3-10.2) and higher organ failure score (1.4, 1.2-1.5). In ICU, 73 % (71-76 %) of patients received acid suppressants; most received proton pump inhibitors. In patients with clinically important GI bleeding, crude and adjusted odds for mortality were 3.7 (1.7-8.0) and 1.7 (0.7-4.3), respectively. In ICU patients clinically important GI bleeding is rare, and acid suppressants are frequently used. Co-existing diseases, liver failure, coagulopathy and organ failures are the main risk factors for GI bleeding. Clinically important GI bleeding was not associated with increased adjusted 90-day mortality, which largely can be explained by severity of comorbidity, other organ failures and age.
10.	Oudin Åström, Daniel, et al. (författare) Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics 2022 Ingår i: Global health action. - : Informa UK Limited. - 1654-9880 .- 1654-9880 .- 1654-9716. ; 15:1 Tidskriftsartikel (refereegranskat)abstract We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (<=-5 degrees C) and hot temperatures (>= 21 degrees C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.
11.	Perner, Anders, et al. (författare) Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis 2012 Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:2, s. 124-134 Tidskriftsartikel (refereegranskat)abstract BACKGROUND Hydroxyethyl starch (HES) 130/0.4 is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.4 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.4 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.4 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.
12.	Akkoyun, S., et al. (författare) AGATA - Advanced GAmma Tracking Array 2012 Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087 .- 1872-9576. ; 668, s. 26-58 Tidskriftsartikel (refereegranskat)abstract The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation γ-ray spectrometer. AGATA is based on the technique of γ-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a γ ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of γ-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector- response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer. © 2011 Elsevier B.V. All rights reserved.
13.	Bartosch-Härlid, Anna, et al. (författare) Life history and the male mutation bias. 2003 Ingår i: Evolution. - 0014-3820. ; 57, s. 2398-2406 Tidskriftsartikel (refereegranskat)
14.	Bauer, Hjärtcentrum, et al. (författare) Monitoring referral and treatment in soft tissue sarcoma : Study based on 1,851 patients from the Scandinavian Sarcoma Group Register 2001 Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 72:2, s. 150-159 Tidskriftsartikel (refereegranskat)abstract This report is based on 1.851 adult patients with soft tissue sarcoma (STS) of the extremities or trunk wall diagnosed between 1986 and 1997 and reported from all tertiary referral centers in Norway and Sweden. The median age at diagnosis was 65 years and the male-to-female ratio was 1.1:1. One third of the tumors were subcutaneous, one third deep, intramuscular and one third deep, extramuscular. The median size was 7 (1-35) cm and 75% were high grade (III-IV). Metastases at presentation were diagnosed in 8% of the patients. Two thirds of STS patients were referred before surgery and the referral practices have improved during the study. The preoperative morphologic diagnosis was made with fine-needle aspiration cytology in 81%, core-needle biopsy in 9% and incisional biopsy in 10%. The frequency of amputations has decreased from 15% in 1986-88 to 9% in 1995-1997. A wide surgical margin was achieved in 77% of subcutaneous and 60% of deep-seated lesions. Overall, 24% of operated STS patients had adjuvant radiotherapy. The use of such therapy at sarcoma centers increased from 20% 1986-88 to 30% in 1995-97. Follow-up has been reported in 96% of the patients. The cumulative local recurrence rate was 0.20 at 5 years and 0.24 at 10 years. The 5-year metastasis-free survival rate was 0.70.
15.	Bentham, James, et al. (författare) A century of trends in adult human height 2016 Ingår i: eLIFE. - 2050-084X. ; 5 Tidskriftsartikel (refereegranskat)abstract Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
16.	Boratynski, Zbyszek, et al. (författare) Increased radiation from Chernobyl decreases the expression of red colouration in natural populations of bank voles (Myodes glareolus) 2014 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4, s. 7141- Tidskriftsartikel (refereegranskat)abstract Pheomelanin is a pink to red version of melanin pigment deposited in skin and hair. Due to its bright colour, pheomelanin plays a crucial function in signalling, in particular sexual signalling. However, production of pheomelanin, as opposed to its dark alternative, eumelanin, bears costs in terms of consumption of antioxidants important for protection of DNA against naturally produced reactive oxidative species. Therefore, decreased expression of pheomelanin is expected in organisms exposed to severe oxidative stress such as that caused by exposure to chronic ionizing radiation. We tested if variable exposure to radiation among natural populations of bank voles Myodes glareolus in Chernobyl affected expression of red colouration in their dorsal fur. The relative redness of dorsal fur was positively correlated with weight, but also negatively correlated with the level of background radiation. These results suggest that the development of the natural red colouration in adult bank voles is affected by ionizing background radiation, and potentially causing elevated levels of oxidative stress. Reduced production of pheomelanin allows more antioxidants to mitigate the oxidative stress caused by radiation. However, changing natural animal colouration for physiological reasons can have ecological costs, if e.g. it causes mismatch with habitat colouration and conspicuousness for predators.
17.	Danaei, Goodarz, et al. (författare) Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants 2015 Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637 Tidskriftsartikel (refereegranskat)abstract Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
18.	Fletcher, Kevin (författare) Causes and consequences of life-history variation : The effects of parasites, glucocorticoids, and environmental conditions in the collared flycatcher (Ficedula albicollis) 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Life-history is the study of all the different stages of life that affect reproductive success and survival between the birth and death of an organism. The reproductive output of an organism is constrained by many things including time, resource, disease agents and environmental conditions. In addition, lineage-specific traits and the limitations of the physiological systems can limit how an organism responds to ecological processes, and thus constrains the variation of life histories represented in nature. Central to the theory of life history are the trade-offs that organisms make during their lifetime to maximise their reproductive potential. In this thesis, I focus on the effect of haemosporidian blood parasites on host life history, in relation to the glucocorticoid response and environmental conditions. The host study species is a population of collared flycatchers (Ficedula albicollis), a species that provides bi-parental care, located in the south of Gotland. We show that nestling condition predicts parasite infection and that parasite-mediated selection can start early on in the birds’ life. We also found a link between Lower levels of glucocorticoids and parasite infection, which might indicate a trade-off between immunity and reproductive effort. Adult birds’ upregulated glucocorticoids in response to an increase in reproductive effort and a predictable change in energy demand during reproduction. I also show that glucocorticoids respond to changing environmental conditions. These results together accentuate the importance of the plasticity of the glucocorticoid response to reproductive success. Moreover, higher levels of hormone during reproduction predicted survival to the next breeding season. In nestlings, glucocorticoid levels increased as a consequence of parent infection status and an increase in reproductive effort. Overall, our results indicate that the glucocorticoid response is context dependent. Finally, female collared flycatchers might pay a fitness cost as a consequence of parasite infection, but can still reproduce successfully suggesting that they can tolerate the parasite. To further our understanding of costs related to parasite infection, we must understand better the mechanisms that enable the host to tolerate infection. This study indicates that glucocorticoids provide a useful tool to detect how wild birds respond to predictable and unpredictable challenges.
19.	Fox, Anthony D., et al. (författare) Current and potential threats to Nordic duck populations - a horizon scanning exercise 2015 Ingår i: Annales Zoologici Fennici. - 0003-455X .- 1797-2450. ; 52:4, s. 193-220 Tidskriftsartikel (refereegranskat)abstract We review the current and future threats to duck populations that breed, stage, moult and/or winter in the Nordic countries. Migratory duck species are sensitive indicators of their changing environment, and their societal value confirms the need to translate signals from changes in their distribution, status and abundance into a better understanding of changes occurring in their wetland environments. We used expert opinion to highlight 25 major areas of anthropogenic change (and touch briefly on potential mitigation measures through nature restoration and reserve management projects) that we consider key issues likely to influence Nordic duck populations now and in the near future to stimulate debate, discussion and further research. We believe such reviews are essential in contributing to development of successful management policy as well as stimulating specific research to support the maintenance of duck species in favourable future conservation status in the face of multiple population pressures and drivers.
20.	Fox, Anthony D., et al. (författare) Current and potential threats to Nordic duck populations - a horizon scanning exercise 2015 Ingår i: Annales Zoologici Fennici. - : Finnish Zoological and Botanical Publishing Board. - 0003-455X. ; 52:4, s. 193-220 Tidskriftsartikel (refereegranskat)abstract We review the current and future threats to duck populations that breed, stage, moult and/or winter in the Nordic countries. Migratory duck species are sensitive indicators of their changing environment, and their societal value confirms the need to translate signals from changes in their distribution, status and abundance into a better understanding of changes occurring in their wetland environments. We used expert opinion to highlight 25 major areas of anthropogenic change (and touch briefly on potential mitigation measures through nature restoration and reserve management projects) that we consider key issues likely to influence Nordic duck populations now and in the near future to stimulate debate, discussion and further research. We believe such reviews are essential in contributing to development of successful management policy as well as stimulating specific research to support the maintenance of duck species in favourable future conservation status in the face of multiple population pressures and drivers.
21.	Guillemain, Matthieu, et al. (författare) Effects of climate change on European ducks: what do we know and what do we need to know? 2013 Ingår i: Wildlife Biology. - : Wiley. - 0909-6396 .- 1903-220X. ; 19:4, s. 404-419 Forskningsöversikt (refereegranskat)abstract The consequences of climate change for bird populations have received much attention in recent decades, especially amongst cavity-nesting songbirds, yet little has been written on ducks (Anatidae) despite these being major elements of wetland diversity and important quarry species. This paper reviews the major known consequences of climate change for birds in general, and relates these to the limited information available specifically for ducks. Climate change can influence migration distance and phenology, potentially affecting patterns of mortality, as well as distribution and reproductive success in ducks. Studies addressing effects of climate change are, however, restricted to very few duck species, including mallard Anas platyrhynchos and common eider Somateria mollissima. Shifts in winter duck distributions have been observed, whereas the mismatch hypothesis (mistiming between the periods of peak energy requirements for young and the peak of seasonal food availability) has received limited sup-port with regard to ducks. We propose a range of monitoring initiatives, including population surveys, breeding success monitoring schemes and individual duck marking, which should later be integrated through population modelling and adaptive management to fill these gaps.
22.	Gustafsson, J., et al. (författare) Atherosclerosis in systemic lupus erythematosus (SLE) and controls : an analysis of SLE subgroups 2014 Ingår i: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 43:S127, s. 7-8 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
23.	Gustafsson, Johanna, et al. (författare) Atherosclerosis In Systemic Lupus Erythematosus (SLE) and Controls, -An Analysis Of SLE Subgroups 2013 Ingår i: Arthritis and Rheumatism. - 0004-3591 .- 1529-0131. ; 65:Suppl. 10, s. S1243-S1243 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
24.	Hou, Mingyan, et al. (författare) Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure 1999 Ingår i: Life Sciences. - 1879-0631. ; 65:11, s. 1195-1206 Tidskriftsartikel (refereegranskat)abstract We wanted to study the expression of P2-receptors at the mRNA-level in the heart and if it is affected by congestive heart failure (CHF). To quantify the P2 receptor mRNA-expression we used a competitive RT-PCR protocol which is based on an internal RNA standard. The P2 receptor mRNA-expression was quantified in hearts from CHF rats and compared to sham-operated rats. Furthermore, the presence of receptor mRNA was studied in the myocardium from patients with heart failure. In the sham operated rats the G-protein coupled P2Y-receptors were expressed at a higher level than the ligand gated ion-channel receptor (P2X1). Among the P2Y-receptors the P2Y6-receptor was most abundantly expressed (P2Y6 > P2Y1 > P2Y2 = P2Y4 > P2X1). A prominent change was seen for the P2X1- and P2Y2-receptor mRNA levels which were increased 2.7-fold and 4.7-fold respectively in the myocardium from the left ventricle of CHF-rats. In contrast, the P2Y1-, P2Y4- and P2Y6-receptor mRNA levels were not significantly altered in CHF rats. In human myocard the P2X1-, P2Y1-, P2Y2-, P2Y6- and P2Y11-receptors were detected by RT-PCR in both right and left atria and ventricles, while the P2Y4-receptor band was weak or absent. In conclusion, most of the studied P2-receptors were expressed in both rat and human hearts. Furthermore, the P2X1- and P2Y2-receptor mRNA were upregulated in CHF, suggesting a pathophysiological role for these receptors in the development of heart failure.
25.	Johansen, J, et al. (författare) Evaluation of Tet-on system to avoid transgene downregulation in ex vivo gene transfer to the CNS 2002 Ingår i: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 9:19, s. 1291-1301 Tidskriftsartikel (refereegranskat)abstract Ex vivo gene transfer to the CNS has so far been hampered by instability of transgene expression. To avoid the phenomenon of transgene down-regulation, we have employed strong, constitutive promoters and compared this expression system with the inducible Tet expression system incorporated in a single plasmid vector or in lentiviral vectors. Plasmid-based transgene expression directed by the constitutive, human ubiquitin promoter, UbC, was stable in transfected HiB5 cells in vitro and comparable in strength to the CMV promoter. However, after transplantation of UbC and CMV HiB5 clones to the rat striatum, silencing of the transgene occurred in most cells soon after implantation of transfected cells. The Tet-on elements were incorporated in a single plasmid vector and inducible HiB5 clones were generated. Inducible clones displayed varying basal expression activity, which could not be ascribed to an effect of cis-elements in the vector, but rather was due, at least in part, to intrinsic activity of the minimal promoter. Basal expression activity could be blocked in a majority of cells by stable expressing the transrepressor tTS. Fully induced expression levels were comparable to CMV and UbC promoters. Similar to the constitutive promoters transgene expression was down-regulated soon after grafting of Inducible HiB5 clones to the rat striatum. Lentiviral vectors can direct long-term stable in vivo transgene expression. To take advantage of this quality of the lentiviral vector, the Tet-on elements were incorporated in two lentiviral transfer vectors followed by transduction of Hib5 cells. Interestingly, all HiB5 clones established by lentiviral transduction showed very similar expression patterns and tight regulatability that apparently was independent of transgene copy number and integration site. Nevertheless, transgene expression in all lentiviral HiB5 clones was down-regulated shortly after transplantation to the rat striatum. These results confirm the general phenomenon of transgene down-regulation. Moreover, the results suggest that the considerable advantages offered by lentiviral vectors for direct gene delivery cannot necessarily be transferred directly to ex vivo gene delivery. This emphasizes the need for alternative vector strategies for ex vivo gene transfer.
26.	Kofoed, Kristian, et al. (författare) Low Prevalence of Oral and Nasal Human Papillomavirus in Employees Performing CO2-laser Evaporation of Genital Warts or Loop Electrode Excision Procedure of Cervical Dysplasia 2015 Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 95:2, s. 173-176 Tidskriftsartikel (refereegranskat)abstract Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV-related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p=0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0% P=0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts.
27.	Laake, Jon Henrik, et al. (författare) Patient characteristics, management and outcomes in a Nordic subset of the "large observational study to understand the global impact of severe acute respiratory failure" : (LUNG SAFE) study 2022 Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 66:6, s. 684-695 Tidskriftsartikel (refereegranskat)abstract Background The "Large observational study to understand the global impact of severe acute respiratory failure" (LUNG SAFE) study described the worldwide epidemiology and management of patients with acute hypoxaemic respiratory failure (AHRF). Here, we present the Nordic subset of data from the LUNG SAFE cohort.Methods We extracted LUNG SAFE data for adults fulfilling criteria for AHRF in intensive care units (ICU) in Denmark, Norway and Sweden, including demographics, co-morbidities, clinical assessment and management characteristics, 90-day survival and length-of-stay (LOS). We analysed ICU LOS with linear regression, and associations between risk factors and mortality were quantified using Cox regression.Results We included 192 patients, with a median age of 64 years (IQR 55, 72), and a male-to-female ratio of 2:1. The majority had one or more co-morbidities, and clinicians identified pneumonia as the primary cause of respiratory failure in 56% and acute respiratory distress syndrome (ARDS) in 21%. Median ICU LOS and duration of invasive mechanical ventilation (IMV) were 5 and 3 days. Tidal volumes (TV) were frequently larger than that supported by evidence and IMV allowing for spontaneous ventilation was common. Younger age, co-morbidity, surgical admission and ARDS were associated with ICU LOS. Sixty-one patients (32%) were dead at 90 days. Age and a non-surgical cause of admission were associated with death.Conclusions In this subset of LUNG SAFE, ARDS was often not recognised in patients with AHRF and management frequently deviated from evidence-based practices. ICU LOS was generally short, and mortality was attributable to known risk factors.
28.	Lambrechts, Marcel M., et al. (författare) The design of artificial nestboxes for the study of secondary hole-nesting birds: a review of methodological inconsistencies and potential biases 2010 Ingår i: Acta Ornithologica. - 0001-6454 .- 1734-8471. ; 45:1, s. 1-26 Tidskriftsartikel (refereegranskat)abstract The widespread use of artificial nestboxes has led to significant advances in our knowledge of the ecology, behaviour and physiology of cavity nesting birds, especially small passerines Nestboxes have made it easier to perform routine monitoring and experimental manipulation of eggs or nestlings, and also repeatedly to capture, identify and manipulate the parents However, when comparing results across study sites the use of nestboxes may also Introduce a potentially significant confounding variable in the form of differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained However, the use of nestboxes may also introduce an unconsidered and potentially significant confounding variable clue to differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained Here we review to what extent the characteristics of artificial nestboxes (e g size, shape, construction material, colour) are documented in the 'methods' sections of publications involving hole-nesting passerine birds using natural or excavated cavities or artificial nestboxes for reproduction and roosting Despite explicit previous recommendations that authors describe in detail the characteristics of the nestboxes used, we found that the description of nestbox characteristics in most recent publications remains poor and insufficient We therefore list the types of descriptive data that should be included in the methods sections of relevant manuscripts and justify this by discussing how variation in nestbox characteristics can affect or confound conclusions from nestbox studies We also propose several recommendations to improve the reliability and usefulness of research based on long-term studies of any secondary hole-nesting species using artificial nestboxes for breeding or roosting.
29.	Lindehall, Birgitta, 1946, et al. (författare) Psychosocial factors in teenagers and young adults with myelomeningocele and clean intermittent catheterization 2008 Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 42:6, s. 539-544 Tidskriftsartikel (refereegranskat)
30.	Lohmander, Anette, et al. (författare) Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 4. Speech outcomes in 5-year-olds - velopharyngeal competency and hypernasality 2017 Ingår i: Journal of Plastic Surgery and Hand Surgery. - : TAYLOR & FRANCIS LTD. - 2000-656X .- 2000-6764. ; 51:1, s. 27-37 Tidskriftsartikel (refereegranskat)abstract Background and aim: Adequate velopharyngeal function and speech are main goals in the treatment of cleft palate. The objective was to investigate if there were differences in velopharyngeal competency (VPC) and hypernasality at age 5 years in children with unilateral cleft lip and palate (UCLP) operated on with different surgical methods for primary palatal repair. A secondary aim was to estimate burden of care in terms of received additional secondary surgeries and speech therapy. Design: Three parallel group, randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Sweden, Norway, and the UK. Methods: Three different surgical protocols for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with a non-syndromic UCLP. Speech audio and video recordings of 391 children (136 girls, 255 boys) were available and perceptually analysed. The main outcome measures were VPC and hypernasality from blinded assessments. Results: There were no statistically significant differences between the prevalences in the arms in any of the trials. VPC: Trial 1, A: 58%, B: 61%; Trial 2, A: 57%, C: 54%; Trial 3, A: 35%, D: 51%. No hypernasality: Trial 1, A: 54%, B: 44%; Trial 2, A: 47%, C: 51%; Trial 3, A: 34%, D: 49%. Conclusions: No differences were found regarding VPC and hypernasality at age 5 years after different methods for primary palatal repair. The burden of care in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed.
31.	Malm, Carl Johan, et al. (författare) Dual or single antiplatelet therapy after coronary surgery for acute coronary syndrome (TACSI trial): Rationale and design of an investigator-initiated, prospective, multinational, registry-based randomized clinical trial 2023 Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 259, s. 1-8 Tidskriftsartikel (refereegranskat)abstract The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investor-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG.
32.	Malmsjö, Malin, et al. (författare) Congestive heart failure induces downregulation of P2X1-receptors in resistance arteries 1999 Ingår i: Cardiovascular Research. - 1755-3245. ; 43:1, s. 219-227 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Congestive heart failure (CHF) is accompanied by enhanced peripheral sympathetic nerve activity, increased vascular resistance and impaired peripheral blood flow. Besides noradrenaline and neuropeptide Y, the sympathetic nervous system also releases ATP, which has contractile effects mediated by different subtypes of P2-receptors on the vascular smooth muscle cells. The present study was designed to examine postsynaptic changes of the contractile responses to ATP and other extracellular nucleotides in CHF. METHODS: CHF was induced by left coronary artery ligation resulting in a reproducible myocardial infarction in Sprague-Dawley rats. Contractile responses were examined in cylindrical segments of aorta and the mesenteric artery after endothelium removal. To determine if an altered response was regulated on the transcriptional level, competitive reverse transcription polymerase chain reaction (RT-PCR) was used to estimate the amount of P2X1-receptor mRNA. RESULTS: ATP, which is both a P2X1- and a P2Y-receptor agonist, induced a weaker contraction in the mesenteric artery from CHF as compared to sham operated rats. A decrease in both potency and maximum contraction was shown for the selective P2X1-receptor agonist, alpha beta-MeATP, in the mesenteric artery (pEC50 = 6.04 vs. 5.76, Cmax = 57% vs. 33%, sham vs. CHF operated rats), but not in the aorta. Competitive RT-PCR also revealed decreased P2X1-receptor mRNA levels in CHF operated rats in the mesenteric artery (9106 x 10(3) vs. 714 x 10(3) molecules/microgram, sham vs. CHF operated rats), while it remained unaltered in the aorta. To study the P2Y-receptor induced contractile effects, the P2X1-receptors were first desensitised with alpha beta-MeATP (10(-5) M for 8 min). After P2X1-receptors desensitisation, UTP and UDP induced strong contractions in both the mesenteric artery and in the aorta, while ATP and ADP were much less effective. These contractions were not altered by CHF, indicating that vascular contraction mediated by P2Y-receptors are unaffected by CHF. CONCLUSION: CHF induces downregulation of P2X1-receptor stimulated contraction in the mesenteric artery depending on decreased mRNA synthesis for the receptor, while the P2Y-receptor activity remains unchanged. Downregulation of P2X1-receptors appears to be specific for peripheral resistance arteries. This may represent a compensatory response to enhanced peripheral sympathetic nerve activity and increased vascular resistance in CHF.
33.	Middeldorp, Christel M., et al. (författare) The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects 2019 Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300 Tidskriftsartikel (refereegranskat)abstract The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
34.	Mills, James A., et al. (författare) Archiving Primary Data : Solutions for Long-Term Studies 2015 Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 30:10, s. 581-589 Tidskriftsartikel (refereegranskat)abstract The recent trend for journals to require open access to primary data included in publications has been embraced by many biologists, but has caused apprehension amongst researchers engaged in long-term ecological and evolutionary studies. A worldwide survey of 73 principal investigators (PIs) with long-term studies revealed positive attitudes towards sharing data with the agreement or involvement of the PI, and 93% of PIs have historically shared data. Only 8% were in favor of uncontrolled, open access to primary data while 63% expressed serious concern. We present here their viewpoint on an issue that can have non-trivial scientific consequences. We discuss potential costs of public data archiving and provide possible solutions to meet the needs of journals and researchers.
35.	Moller, Anders Pape, et al. (författare) Clutch-size variation in Western Palaearctic secondary hole-nesting passerine birds in relation to nest box design 2014 Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 5:4, s. 353-362 Tidskriftsartikel (refereegranskat)abstract Secondary hole-nesting birds that do not construct nest holes themselves and hence regularly breed in nest boxes constitute important model systems for field studies in many biological disciplines with hundreds of scientists and amateurs involved. Those research groups are spread over wide geographic areas that experience considerable variation in environmental conditions, and researchers provide nest boxes of varying designs that may inadvertently introduce spatial and temporal variation in reproductive parameters. We quantified the relationship between mean clutch size and nest box size and material after controlling for a range of environmental variables in four of the most widely used model species in the Western Palaearctic: great tit Parus major, blue tit Cyanistes caeruleus, pied flycatcher Ficedula hypoleuca and collared flycatcher F.albicollis from 365 populations and 79610 clutches. Nest floor area and nest box material varied non-randomly across latitudes and longitudes, showing that scientists did not adopt a random box design. Clutch size increased with nest floor area in great tits, but not in blue tits and flycatchers. Clutch size of blue tits was larger in wooden than in concrete nest boxes. These findings demonstrate that the size of nest boxes and material used to construct nest boxes can differentially affect clutch size in different species. The findings also suggest that the nest box design may affect not only focal species, but also indirectly other species through the effects of nest box design on productivity and therefore potentially population density and hence interspecific competition.
36.	Moller, Anders Pape, et al. (författare) Effects of interspecific coexistence on laying date and clutch size in two closely related species of hole-nesting birds 2018 Ingår i: Journal of Animal Ecology. - : WILEY. - 0021-8790 .- 1365-2656. ; 87:6, s. 1738-1748 Tidskriftsartikel (refereegranskat)abstract Coexistence between great tits Parus major and blue tits Cyanistes caeruleus, but also other hole-nesting taxa, constitutes a classic example of species co-occurrence resulting in potential interference and exploitation competition for food and for breeding and roosting sites. However, the spatial and temporal variations in coexistence and its consequences for competition remain poorly understood. We used an extensive database on reproduction in nest boxes by great and blue tits based on 87 study plots across Europe and Northern Africa during 1957-2012 for a total of 19,075 great tit and 16,729 blue tit clutches to assess correlative evidence for a relationship between laying date and clutch size, respectively, and density consistent with effects of intraspecific and interspecific competition. In an initial set of analyses, we statistically controlled for a suite of site-specific variables. We found evidence for an effect of intraspecific competition on blue tit laying date (later laying at higher density) and clutch size (smaller clutch size at higher density), but no evidence of significant effects of intraspecific competition in great tits, nor effects of interspecific competition for either species. To further control for site-specific variation caused by a range of potentially confounding variables, we compared means and variances in laying date and clutch size of great and blue tits among three categories of difference in density between the two species. We exploited the fact that means and variances are generally positively correlated. If interspecific competition occurs, we predicted a reduction in mean and an increase in variance in clutch size in great tit and blue tit when density of heterospecifics is higher than the density of conspecifics, and for intraspecific competition, this reduction would occur when density of conspecifics is higher than the density of heterospecifics. Such comparisons of temporal patterns of means and variances revealed evidence, for both species, consistent with intraspecific competition and to a smaller extent with interspecific competition. These findings suggest that competition associated with reproductive behaviour between blue and great tits is widespread, but also varies across large spatial and temporal scales.
37.	Moller, Anders P., et al. (författare) Variation in clutch size in relation to nest size in birds 2014 Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:18, s. 3583-3595 Tidskriftsartikel (refereegranskat)abstract Nests are structures built to support and protect eggs and/or offspring from predators, parasites, and adverse weather conditions. Nests are mainly constructed prior to egg laying, meaning that parent birds must make decisions about nest site choice and nest building behavior before the start of egg-laying. Parent birds should be selected to choose nest sites and to build optimally sized nests, yet our current understanding of clutch size-nest size relationships is limited to small-scale studies performed over short time periods. Here, we quantified the relationship between clutch size and nest size, using an exhaustive database of 116 slope estimates based on 17,472 nests of 21 species of hole and non-hole-nesting birds. There was a significant, positive relationship between clutch size and the base area of the nest box or the nest, and this relationship did not differ significantly between open nesting and hole-nesting species. The slope of the relationship showed significant intraspecific and interspecific heterogeneity among four species of secondary hole-nesting species, but also among all 116 slope estimates. The estimated relationship between clutch size and nest box base area in study sites with more than a single size of nest box was not significantly different from the relationship using studies with only a single size of nest box. The slope of the relationship between clutch size and nest base area in different species of birds was significantly negatively related to minimum base area, and less so to maximum base area in a given study. These findings are consistent with the hypothesis that bird species have a general reaction norm reflecting the relationship between nest size and clutch size. Further, they suggest that scientists may influence the clutch size decisions of hole-nesting birds through the provisioning of nest boxes of varying sizes.
38.	Moller-Kristensen, Mette, et al. (författare) Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through the MBL pathway 2007 Ingår i: International Immunology. - : Oxford University Press (OUP). - 1460-2377 .- 0953-8178. ; 19:2, s. 141-149 Tidskriftsartikel (refereegranskat)abstract The complement system is an important part of the innate immune system. Three pathways, the classical, the alternative and the lectin pathway, lead to the cleavage of complement factor C3, a central event in the activation of the complement system. We investigated the deposition of C3b (solid-phase C3 activation product) on a mannan-coated surface at high concentration of human serum (17%). At these conditions, mannan-binding lectin (MBL) promoted the activation of C3 through the combined action of MBL-associated serine protease (MASP)-1 and MASP-2 without appreciable involvement of the alternative pathway. In serum depleted of MASP-1, MASP-2 and MASP-3, we observed synergetic effect of reconstitution with MASP-1 and MASP-2. This was inhibited by MASP-3. No C3b deposition was observed with C2- or C4-depleted serum. Depletion of factor B had no effect on the MBL-MASP-promoted C3b deposition. Our results demonstrate a function of the orphan protease MASP-1 by providing evidence that this enzyme collaborates with MASP-2 in the generation of C3 convertase, a process observable at high serum concentration, but not at low serum concentration.
39.	Morgan, AR, et al. (författare) Inflammatory biomarkers in Alzheimer's disease plasma 2019 Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 15:6, s. 776-787 Tidskriftsartikel (refereegranskat)
40.	Nielsen, Niklas, et al. (författare) Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest 2013 Ingår i: New England Journal of Medicine. - 0028-4793. ; 369:23, s. 2197-2206 Tidskriftsartikel (refereegranskat)abstract BackgroundUnconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. MethodsIn an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. ResultsIn total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. ConclusionsIn unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)
41.	Pagh Moller, Sanne, et al. (författare) Differences in uptake of immunisations and health examinations among refugee children compared to Danish-born children : a cohort study 2016 Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 0340-6199 .- 1432-1076. ; 175:4, s. 539-549 Tidskriftsartikel (refereegranskat)abstract Refugee children and their families constitute a vulnerable group regarding health and access to care. In a register-based cohort design, we examined differences in uptake of immunisations and child health examinations between refugee children and Danish-born children, including predictors of uptake among refugee children. Refugee children (n = 16,701) who, between January 1993 and December 2010, obtained residency permits in Denmark were included and matched in a 1:6 ratio on age and sex with Danish-born children (n = 100,206). Personal identification numbers were cross-linked to the National Danish Health Service Register, identifying all contacts for immunisation and child health examinations. We estimated hazard ratios (HR) of uptake. Refugee children had a lower uptake of all immunisations compared to Danish-born children. The lowest uptake was found for immunisation against diphtheria, tetanus, pertussis and polio (HR = 0.50; 95 % confidence interval (CI) 0.48–0.51). Participation in child health examinations was also lower among refugee children with the lowest at the last child health examination at age 5 (HR = 0.48; 95 % CI 0.47–0.50). Adjusting the analysis for parental income increased the HRs by 10–20 %.Conclusion: This Danish register-based study using nationwide data revealed a lower uptake of routine immunisations and child health examinations among refugee children compared to Danish-born children.
42.	Robinson, Anna-Lena, 1971-, et al. (författare) C2 Fracture Subtypes, Incidence, and Treatment Allocation Change with Age : A Retrospective Cohort Study of 233 Consecutive Cases 2017 Ingår i: BioMed Research International. - : HINDAWI LTD. - 2314-6133 .- 2314-6141. Tidskriftsartikel (refereegranskat)abstract The currently available data on the distribution of C2 fracture subtypes is sparse. This study was designed to identify the proportions of the second cervical vertebra (C2) fracture subtypes and to present age and gender specific incidences of subgroups. A dataset of all patients treated between 2002 and 2014 for C2 fractures was extracted from the regional hospital information system. C2 fractures were classified into odontoid fractures types 1, 2, and 3, Hangman's fractures types 1, 2, and 3, and atypical C2 fractures. 233 patients (female 51%, age 72 +/- 19 years) were treated for a C2 fracture. Odontoid fractures were found in 183 patients, of which 2 were type 1, 127 type 2, and 54 type 3, while 26 of C2 fractures were Hangman's fractures and 24 were atypical C2 fractures. In the geriatric subgroup 89% of all C2 fractures were odontoid, of which 71% were type 2 and 29% type 3. There was an increasing incidence of odontoid fractures types 2 and 3 from 2002 to 2014. 40% of C2 fractures were treated surgically. This study presents reliable subset proportions of C2 fractures in a prospectively collected regional cohort. Knowledge of these proportions facilitates future epidemiological studies of C2 fractures.
43.	Ryd, L., et al. (författare) Pre-Osteoarthritis: Definition and Diagnosis of an Elusive Clinical Entity 2015 Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 6:3, s. 156-165 Tidskriftsartikel (refereegranskat)abstract Objective. An attempt to define pre-osteoarthritis (OA) versus early OA and definitive osteoarthritis. Methods. A group of specialists in the field of cartilage science and treatment was formed to consider the nature of OA onset and its possible diagnosis. Results. Late-stage OA, necessitating total joint replacement, is the end stage of a biological process, with many previous earlier stages. Early-stage OA has been defined and involves structural changes identified by arthroscopy or radiography. The group argued that before the "early-stage OA" there must exist a stage where cellular processes, due to the presence of risk factors, have kicked into action but have not yet resulted in structural changes. The group suggested that this stage could be called "pre-osteoarthritis" (pre-OA). Conclusions. The group suggests that defining points of initiation for OA in the knee could be defined, for example, by traumatic episodes or surgical meniscectomy. Such events may set in motion metabolic processes that could be diagnosed by modern MRI protocols or arthroscopy including probing techniques before structural changes of early OA have developed. Preventive measures should preferably be applied at this pre-OA stage in order to stop the projected OA epidemic.
44.	Stengaard-Pedersen, K, et al. (författare) Inherited deficiency of mannan-binding lectin-associated serine protease 2 2003 Ingår i: New England Journal of Medicine. - 0028-4793. ; 349:6, s. 554-560 Tidskriftsartikel (refereegranskat)
45.	Svenningsson, Anders, et al. (författare) Natalizumab Reduces Fatigue as Measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC) - First Results from the TYNERGY Trial 2012 Ingår i: Neurology. - Philadelphia : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 78:Suppl 1, s. P07081- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
46.	Teplitsky, Celine, et al. (författare) Assessing Multivariate Constraints to Evolution across Ten Long-Term Avian Studies 2014 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e90444- Tidskriftsartikel (refereegranskat)abstract Background: In a rapidly changing world, it is of fundamental importance to understand processes constraining or facilitating adaptation through microevolution. As different traits of an organism covary, genetic correlations are expected to affect evolutionary trajectories. However, only limited empirical data are available. Methodology/Principal Findings: We investigate the extent to which multivariate constraints affect the rate of adaptation, focusing on four morphological traits often shown to harbour large amounts of genetic variance and considered to be subject to limited evolutionary constraints. Our data set includes unique long-term data for seven bird species and a total of 10 populations. We estimate population-specific matrices of genetic correlations and multivariate selection coefficients to predict evolutionary responses to selection. Using Bayesian methods that facilitate the propagation of errors in estimates, we compare (1) the rate of adaptation based on predicted response to selection when including genetic correlations with predictions from models where these genetic correlations were set to zero and (2) the multivariate evolvability in the direction of current selection to the average evolvability in random directions of the phenotypic space. We show that genetic correlations on average decrease the predicted rate of adaptation by 28%. Multivariate evolvability in the direction of current selection was systematically lower than average evolvability in random directions of space. These significant reductions in the rate of adaptation and reduced evolvability were due to a general nonalignment of selection and genetic variance, notably orthogonality of directional selection with the size axis along which most (60%) of the genetic variance is found. Conclusions: These results suggest that genetic correlations can impose significant constraints on the evolution of avian morphology in wild populations. This could have important impacts on evolutionary dynamics and hence population persistence in the face of rapid environmental change.
47.	Willadsen, Elisabeth, et al. (författare) Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 5. Speech outcomes in 5-year-olds - consonant proficiency and errors 2017 Ingår i: Journal of Plastic Surgery and Hand Surgery. - : TAYLOR & FRANCIS LTD. - 2000-656X .- 2000-6764. ; 51:1, s. 38-51 Tidskriftsartikel (refereegranskat)abstract Background and aim: Normal articulation before school start is a main objective in cleft palate treatment. The aim was to investigate if differences exist in consonant proficiency at age 5 years between children with unilateral cleft lip and palate (UCLP) randomised to different surgical protocols for primary palatal repair. A secondary aim was to estimate burden of care in terms of received additional secondary surgeries and speech therapy. Design: Three parallel group, randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Norway, Sweden, and the UK. Methods: Three different surgical protocols for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with non-syndromic UCLP. Speech audio- and video-recordings of 391 children (136 girls and 255 boys) were available and transcribed phonetically. The main outcome measure was Percent Consonants Correct (PCC) from blinded assessments. Results: In Trial 1, arm A showed statistically significant higher PCC scores (82%) than arm B (78%) (p=.045). No significant differences were found between prevalences in Trial 2, A: 79%, C: 82%; or Trial 3, A: 80%, D: 85%. Across all trials, girls achieved better PCC scores, excluding s-errors, than boys (91.0% and 87.5%, respectively) (p=.01). Conclusions: PCC scores were higher in arm A than B in Trial 1, whereas no differences were found between arms in Trials 2 or 3. The burden of care in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed.

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