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Background: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.Objective: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).Methods: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.Results: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10-3 ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P = 1.15 × 10-7 ), but not in ULSAM (β, -0.034, P = 0.16).Conclusions: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee. [ABSTRACT FROM AUTHOR]

Background: Both insufficient exposure to sunlight and vitamin D deficiency have been associated with an increased risk for multiple sclerosis (MS). An interaction between human leukocyte antigen HLA-DRB1*15 and vitamin D in MS was recently proposed. We investigated the association between previous exposure to ultraviolet radiation (UVR), vitamin D status at inclusion in the study, and MS risk including the interaction of these factors with HLA-DRB1*15. Methods: A population-based case-control study involving 1013 incident cases of MS and 1194 controls was performed in Sweden during 2005-2010. Subjects were classified according to their UVR exposure habits, vitamin D status, and HLA genotypes. The associations between different sun exposure habits/vitamin D levels and MS were calculated as odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. Potential interaction was evaluated by calculating the attributable proportion due to interaction. Results: Subjects with low UVR exposure had a significantly increased risk of MS compared with those who reported the highest exposure (OR 2.2, 95% CI 1.5-3.3). Similarly, subjects who had 25-hydroxy-vitamin D levels less than 50 nM/l had an increased risk for MS (OR 1.4, 95% CI 1.2-1.7). The association between UVR exposure and MS risk persisted after adjustment for vitamin D status. There was no interaction with HLA-DRB1*15 carriage. Conclusions: UVR and vitamin D seem to affect MS risk in adults independently of HLA-DRB1*15 status. UVR exposure may also exert a protective effect against developing MS via other pathways than those involving vitamin D. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of a new first trimester web-based software for the detection of chromosomal anomalies using a combination of ultrasound and biochemistry.Design: Registry-based cohort study.Setting: Ultrasound units in the Stockholm region.Population: 20 710 women with singleton pregnancies were examined at 11(+0) to 13(+6) weeks' gestational age during a three-year period 2006-2009.Methods: The risks for trisomy 21, 13 and 18 were calculated using a combination of maternal age, serum markers and nuchal translucency. Individual risk estimates were calculated and then reported to a web-based system using a new algorithm based on likelihood ratios of each marker derived from Gaussian distributions in normal and affected pregnancies.Main Outcome Measures: The impact on rates of invasive testing and the incidence of children born with Down's syndrome after implementing the method.Results: Approximately a third of all pregnant women in the region were examined with the combined test. The detection and test positive rates for Down's syndrome was 90 and 6.8%, respectively. Invasive testing among pregnant women decreased from 15 to 8% after introducing the method but the incidence of children born with Down's syndrome did not decrease during the study period.Conclusion: The new web-based software is an effective method for the detection of trisomy 21 with similar performance compared to other programs. However, it needs to be offered to all pregnant women to have an impact on the incidence of Down's syndrome. [ABSTRACT FROM AUTHOR]

Burgers vectors of matrix dislocations in mullite have been determined by the defocus large-angle convergent beam electron diffraction technique. Vectors of the types [100], [010], [110] and [112] were identified. These Burgers vectors are discussed in relation to the open channels and the oxygen vacancy distribution in the mullite structure. It is suggested that a short-range ordering of oxygen vacancies may account for a Burgers vector of the type [112]. [ABSTRACT FROM AUTHOR]

Objectives: Cardiac troponin T (cTnT) is a highly sensitive and specific marker of myocardial damage. It has been shown that elevated serum concentrations of cTnT in haemodialysis (HD) patients are associated with poor prognostic outcome. The aim of the present study was to investigate the predictive value of cTnT in samples from predialysis patients and to investigate associations between cTnT and inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6).Design: Cohort, follow-up study.Setting: Huddinge University Hospital, Sweden.Subjects: A total of 115 (62% males, 28% diabetic patients) end-stage renal disease (ESRD) patients (52 +/- 1 years), of which 29% had cardiovascular disease (CVD), were studied shortly before the onset of dialysis therapy. Sixty-four patients started peritoneal dialysis (PD) as renal replacement therapy, whilst 49 started HD during the follow-up.Main Outcome Measures: The cTnT was analysed with the third generation TnT assay on Elecsys 2010. The prognostic value was calculated for cTnT, IL-6, age, CVD, malnutrition, diabetes mellitus (DM) and gender. Survival analyses were made with Kaplan-Meier and Cox regression analyses, with all-cause mortality as the clinical end point (mean follow-up period 2.7 +/- 0.1 years).Results: Significant correlations were found between cTnT and CKMB (rho = 0.52, P < 0.0001), IL-6 (rho = 0.23, P < 0.05), CRP (rho = 0.30, P < 0.05), and serum albumin (rho = -0.31, P < 0.001), respectively. Diabetic patients had higher median serum cTnT level (0.09 microg L-1; range <0.01-0.51 vs. 0.04 microg L-1; range <0.01-0.67 microg L-1; P < 0.005) compared with nondiabetic patients. Likewise, patients with CVD had a significantly higher median level (0.08 microg L-1; range <0.01-0.67 microg L-1 vs. 0.04 microg L-1; range <0.01-0.61 microg L-1; P < 0.01) of cTnT compared with patients without CVD. Patients with cTnT > or =0.10 microg L-1 had a higher cumulative mortality rate than patients with cTnT < 0.10 microg L-1 (chi2 = 7.04; P < 0.01). Whilst age, CVD, malnutrition, DM, IL-6, cTnT and male gender were associated with poor outcome in the univariate analysis, only DM (P < 0.05) and cTnT (P < 0.05) were independently associated with mortality in a multivariate analysis.Conclusions: The present study demonstrates that serum concentrations of cTnT > or =0.10 microg L-1 is a significant predictor of mortality in patients starting dialysis. Moreover, the positive correlations between cTnT and IL-6, and CRP, respectively, suggest an association between inflammation and cTnT levels. Finally, the results of the present study suggest that cTnT is an independent predictor of mortality in ESRD patients starting dialysis. [ABSTRACT FROM AUTHOR]

Gymnadenia conopsea (L.) R. Br., or the fragrant orchid, is one of many plant species negatively influenced by new practices in agriculture and forestry during the last decades. This study describes the level of microsatellite variation within and among 10 Swedish populations of this species. It was not possible to detect strong effects of small population size or fragmentation. In general, the species had high genetic variation within and low genetic divergence among populations, although the correlation between population size and number of alleles was close to significance at the 95% level. Also, a significant isolation by distance effect was observed, indicating the presence of modest restrictions in gene dispersal between the investigated populations. [ABSTRACT FROM AUTHOR]

Objective To investigate the possible relationship between serum levels of prostate specific antigen (PSA), dihydrotestosterone (DHT), testosterone, sexual-hormone binding globulin (SHBG) and tumour stage, grade and ploidy in 65 cases of prostate cancer diagnosed in a screening study compared to 130 controls from the same population. Patients, subjects and methods From a population of 26602 men between the ages of 55 and 70 years, 2400 were selected randomly and invited to undergo screening for prostate cancer using a digital rectal examination, transrectal ultrasonography and PSA analysis. Among the 1782 attendees, 65 cases of prostate cancer were diagnosed. Each case was matched with two control subjects of similar age and prostate volume from the screening population. Frozen serum samples were analysed for PSA, DHT, testosterone and SHBG, and compared to the diagnosis and tumour stage, grade and ploidy. Comparisons between these variables, and multivariate and regression analyses were performed. Results There were significant differences in PSA level with all variables except tumour ploidy. DHT levels were slightly lower in patients with prostate cancer but the difference was not statistically significant. There was a trend towards lower DHT values in more advanced tumours and the difference for T-stages was close to statistical significance ( P=0.059). Testosterone levels were lower in patients with cancer than in the control group, but the differences were not significant. There was no correlation between testosterone levels, tumour stage and ploidy, but the differences in testosterone level in tumours of a low grade of differentiation compared to those with intermediate and high grade was nearly significant ( P=0.058). The testosterone/DHT ratio tended to be higher in patients with more advanced tumours. SHBG levels were lower in patients with cancer than in controls but the differences were not statistically significant. There were no systematic variations of tumour stage, grade and ploidy. Multivariate analysis showed that if the PSA level was known, then DHT, testosterone or SHBG added no further information concerning diagnosis, stage, grade or ploidy. Regression analysis on T-stage, PSA level and DHT showed an inverse linear relationship between PSA and DHT for stage T-3 ( P=0.035), but there was no relationship between PSA and testosterone. Conclusion PSA was of value in discriminating between cases and controls and between various tumour stages and grades, but no statistically significant correlation was found for ploidy. If PSA level was known, no other variable added information in individual cases. Within a group, DHT levels tended to be lower among cases and in those with more advanced tumours. There was an inverse relationship between tumour volume, as defined by PSA level, and 5α-reductase activity, as defined by DHT level, and the testosterone/DHT ratio. This trend was most obvious with T-stage. No systematic variation were found in the levels of testosterone or SHBG. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Screening for Down syndrome in the first trimester: the Stockholm experience of a new web-based system," by P. Conner, and colleagues is presented.

An abstract of the research paper "First trimester serum biochemistry and screen positive rates in 3 consecutive pregnancies," by P. Conner and colleagues is presented.

Load management is one means of reducing maximum electricity load, and hence also the cost of electricity. In Sweden, the amount charged during the maximum load hour might be about 200 times higher than thestandard charge for one kilowatt-hour. If the load could be reduced by certain equipment in factories and buildings, the need for new power stations and higher capacity in the grid would also be decreased. Using electricity load data for one full year and a short computer program, this paper shows by how much the load could be reduced by postponing demand. If part of the load could be postponed by only one hour, this part may need to be only very small for maximum benefit. If longer time segments were practicable, larger chunks could be transferred. The main result of the study is, however, that load management in practice is a very subtle task if an optimal solution is to be achieved. [ABSTRACT FROM AUTHOR]

Background: Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%-49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high., Methods and Results: We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within-person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within-person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later., Conclusions: LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.

Background We recently reported a link between plasma levels of 2 of 84 cardiovascular disease (CVD)-related proteins and the 3 major CVDs, myocardial infarction, ischemic stroke, and heart failure. The present study investigated whether measurement of almost 10 times the number of proteins could lead to discovery of additional risk markers for CVD. Methods and Results We measured 742 proteins using the proximity extension assay in 826 male participants of ULSAM (Uppsala Longitudinal Study of Adult Men) who were free from CVD at the age of 70 years. Cox proportional hazards models were adjusted for age only, as well as all traditional risk factors. During a 12.5-year median follow-up (maximal, 22.0 years), 283 incident CVDs occurred. Forty-one proteins were significantly (false discovery rate <0.05) related to the combined end point of incident CVD, with N-terminal pro-brain natriuretic peptide as the top finding, while 53 proteins were related to incident myocardial infarction. A total of 13 and 16 proteins were significantly related to incident ischemic stroke and heart failure, respectively. Growth differentiation factor 15, 4-disulfide core domain protein 2, and kidney injury molecule were related to all of the 3 major CVD outcomes. A lasso selection of 11 proteins improved discrimination of incident CVD by 5.0% ( P =0.0038). Conclusions Large-scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.

Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin-angiotensin aldosterone system (RAAS) inhibitor use and COVID-19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID-19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine-learning-derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID-19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74-1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID-19 (HR, 0.92; 95% CI, 0.70-1.22), and 64 died with COVID-19 (HR, 1.22; 95% CI, 0.68-2.19). The severity of COVID-19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89-1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID-19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID-19 pandemic.

Background: Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT., Methods and Results: Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (β=-0.018, P<0.001) in men but not in women (β=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (β=-0.0008, P=0.004) but not in women (β=-0.0003, P=0.522; P for interaction=0.007)., Conclusions: This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Rationale, Aims and Objectives: Improving the possibilities for ageing persons to take control over their health is an increasingly important public health issue. Health promotion has previously been visualized to succeed with this goal, but research has primarily focused on ageing persons who are native-born, leaving the generalizability to persons who are foreign-born unexplored. Therefore, as part of the development of a larger health promotion initiative for ageing persons who have experienced migration, this study aimed to assess the feasibility of an adapted protocol. The specific feasibility objectives were to assess recruitment procedure, retention rates, study questionnaire administration and variability of collected data., Method: Forty persons who were ≥70 years, and who had migrated from Finland, Bosnia and Herzegovina, Croatia, Montenegro or Serbia to Sweden were randomly allocated to a health promotion programme or a control group. The programme was linguistically adapted with regard to translated information material, bilingual health professionals and evaluators, and a person-centred approach was applied to both programme development and provision. The data analysis was explorative and descriptive., Results: The results visualized structural and linguistic barriers to recruitment and study questionnaire administration, and describe strategies for how to bridge them. Retention rates and data variability were satisfying., Conclusions: Calling for iterative and pragmatic programme design, the findings describe how to move towards a more inclusive health care environment. Person-centred and bilingual approaches with attention to the possibilities for building authentic relationships between participants and providers are emphasized, and a structured methodology for developing study questionnaires is suggested., (© 2015 John Wiley & Sons, Ltd.)

Aim: To analyse serum levels of 25-hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development., Method: Four groups of mothers were invited to participate; 20 with Somali origin with at least one child with autism, 20 with Somali origin without a child with autism, 20 of Swedish origin with at least one child with autism and 20 with Swedish origin without a child with autism. Two blood samples were collected from each individual; during autumn and spring., Results: Between 12 and 17 mothers from the different groups accepted to participate, both groups of mothers of Somali origin had significantly lower values of 25-hydroxyvitamin D compared with Swedish mothers. The difference of 25-hydroxyvitamin D between mothers of Somali origin with and without a child with autism was not significant., Conclusion: Our findings of low vitamin D levels in Somali women entail considerable consequences in a public health perspective. The observed tendency, i.e. the lowest values in mothers of Somali origin with a child with autism was in the predicted direction, supporting the need for further research of vitamin D levels in larger samples of Somali mothers of children with and without autism.