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Background: Mental stress is associated with higher mortality, but it remains controversial whether the association is causal or a consequence of a higher physical disease burden in those with a high mental stress load. Understanding causality is important when developing targeted interventions. We aimed to estimate the effect of mental stress on mortality by performing a ‘natural’ experiment using spousal bereavement as a disease-independent mental stressor. Methods: We followed a population-based matched cohort, including all individuals in Denmark bereaved in 1997–2014, for 17 years. Prospectively recorded register data were obtained for civil and vital status, 39 mental and physical diagnoses, and socioeconomic factors. Results: In total, 389 316 bereaved individuals were identified and 137 247 died during follow-up. Bereaved individuals had higher all-cause mortality than non-bereaved references in the entire study period. The relative mortality in the bereaved individuals was highest shortly after the loss (adjusted hazard ratio (aHR), first month: 2.50, 95% confidence interval (CI) 2.37–2.63; aHR, 6–12 months: 1.38, 95% CI 1.34–1.42). The excess mortality rate associated with bereavement rose with increasing number of physical diseases (1.33 v. 7.00 excess death per 1000 person-months for individuals with 0 v. ⩾3 physical conditions during the first month) and was exacerbated by the presence of mental illness. The excess mortality among bereaved individuals was primarily due to death from natural causes. Conclusions: Bereavement was associated with increased short-term and long-term mortality, even after adjustment for morbidities, which suggests that mental stress may play a causal role in excess mortality. [ABSTRACT FROM AUTHOR]

BackgroundThe loss of a close relative is one of the most stressful life events. In pregnancy, this experience has been associated with a higher risk of fetal death and under-five mortality, but little is known about potential effects on long-term mortality in offspring. We examined the association between prenatal maternal bereavement and mortality in a cohort of 5.3 million children followed until up to 37 years of age.MethodThe population-based cohort study included 5 253 508 live singleton births in Denmark (1973–2004) and Sweden (1973–2006). Children born to mothers who lost a child, spouse, sibling, or parent during or 1 year before pregnancy were categorized as exposed.ResultsPrenatal maternal bereavement was associated with a 10% increased all-cause mortality risk in offspring [mortality rate ratio (MRR) 1.10, 95% confidence interval (CI) 1.03–1.18]. The association was the most pronounced for children of mothers who lost a child/spouse (MRR 1.28, 95% CI 1.14–1.44) and was stronger during the first 10 years of life. Prenatal maternal bereavement may have stronger effects on natural causes of death in offspring, including infectious/parasitic disease (MRR 1.86, 95% CI 1.07–3.23), endocrine/nutritional/metabolic diseases (MRR 3.23, 95% CI 2.02–5.17), diseases of nervous system (MRR 3.36, 95% CI 2.47–4.58), and congenital malformations (MRR 1.39, 95% CI 1.08–1.80). No excess mortality risk in offspring was observed for unnatural causes of death.ConclusionPrenatal maternal bereavement was associated with an increased long-term mortality risk in offspring, particularly for selected natural causes of diseases and medical conditions. Our results support the fetal programming hypothesis that prenatal stress may contribute to ill health from physical diseases later in life. [ABSTRACT FROM AUTHOR]

BackgroundMaternal stress during pregnancy may increase the risk of preterm delivery (PD), but the associations between stress and subtypes of PD are not clear. We investigated maternal loss of a close relative and risks of very and moderately PD (<32 and 32–36 weeks, respectively) and spontaneous and medically indicated PD.MethodWe studied 4 940 764 live singleton births in Denmark (1978–2008) and Sweden (1973–2006). We retrieved information on death of women's family members (children, partner, siblings, parents), birth outcomes and maternal characteristics from nationwide registries.ResultsOverall, the death of a close family member the year before pregnancy or in the first 36 weeks of pregnancy was associated with a 7% increased risk of PD [95% confidence interval (CI) 1.04–1.10]. The highest hazard ratios (HR) for PD were found for death of an older child [HR (95% CI) 1.20 (1.10–1.31)] and for death of a partner [HR (95% CI) 1.31 (1.03–1.66)]. These losses were associated with higher risks of very preterm [HR (95% CI) 1.61 (1.29–2.01) and 2.07 (1.15–3.74), respectively] than of moderately preterm [HR (95% CI) 1.14 (1.03–1.26) and 1.22 (0.94–1.58), respectively] delivery. There were no substantial differences in the association between death of a child or partner and the risk of spontaneous v. medically indicated PD.ConclusionsDeath of a close family member the year before or during pregnancy was associated with an increased risk of PD, especially very PD. Possible mechanisms include both spontaneous and medically indicated preterm birth. [ABSTRACT FROM PUBLISHER]

BackgroundPersons with severe mental illness (SMI) have excess mortality, which may partly be explained by their high prevalence of diabetes.MethodWe compared the overall and cause-specific mortality in persons with SMI and diabetes with that of the general Danish population between 1997 and 2009 by linking data from Danish national registries.ResultsThe cohort counted 4 734 703 persons, and during follow-up 651 080 persons died of whom 1083 persons had SMI and diabetes. Compared with the background population, the overall mortality rate ratios (MRRs) for persons with SMI and diabetes were 4.14 [95% confidence interval (CI) 3.81–4.51] for men and 3.13 (95% CI 2.88–3.40) for women. The cause-specific MRRs for persons with SMI and diabetes were lowest for malignant neoplasms (women: MRR = 1.98, 95% CI 1.64–2.39; men: MRR = 2.08, 95% CI 1.69–2.56) and highest for unnatural causes of death (women: MRR = 12.31, 95% CI 6.80–22.28; men: MRR = 7.89, 95% CI 5.51–11.29). The cumulative risks of death within 7 years of diabetes diagnosis for persons with SMI and diabetes were 15.0% (95% CI 12.4–17.6%) for those younger than 50 years, 30.7% (95% CI 27.8–33.4%) for those aged 50–69 years, and 63.8% (95% CI 58.9–68.2%) for those aged 70 years or older. Among persons suffering from both diseases, 33.4% of natural deaths were attributed to diabetes and 14% of natural deaths were attributed to the interaction between diabetes and SMI.ConclusionsLong-term mortality is high for persons with SMI and diabetes. This calls for effective intervention from a coordinated and collaborating healthcare system. [ABSTRACT FROM AUTHOR]

BackgroundMaternal stress during pregnancy is associated with a modestly increased risk of fetal growth restriction and pre-eclampsia. Since placental abruption shares similar pathophysiological mechanisms and risk factors with fetal growth restriction and pre-eclampsia, we hypothesized that maternal stress may be implicated in abruption risk. We investigated the association between maternal bereavement during pregnancy and placental abruption.MethodWe studied singleton births in Denmark (1978–2008) and Sweden (1973–2006) (n = 5 103 272). In nationwide registries, we obtained data on death of women's close family members (older children, siblings, parents, and partners), abruption and potential confounders.ResultsA total of 30 312 (6/1000) pregnancies in the cohort were diagnosed with placental abruption. Among normotensive women, death of a child the year before or during pregnancy was associated with a 54% increased odds of abruption [95% confidence interval (CI) 1.30–1.82]; the increased odds were restricted to women who lost a child the year before or during the first trimester in pregnancy. In the group with chronic hypertension, death of a child the year before or in the first trimester of pregnancy was associated with eight-fold increased odds of abruption (odds ratio 8.17, 95% CI 3.17–21.10). Death of other relatives was not associated with abruption risk.ConclusionsLoss of a child the year before or in the first trimester of pregnancy was associated with an increased risk of abruption, especially among women with chronic hypertension. Studies are needed to investigate the effect of less severe, but more frequent, sources of stress on placental abruption risk. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the effect of increased maternal nutrition in early to mid gestation on changes in serum growth factors of the sow and foetuses. Furthermore, the effect of the foetal sera on in vitro proliferation and differentiation of porcine primary myoblasts was examined. Pregnant sows were either given food either in accordance to requirements (2 kg/day; C) until day 50 or 70 of gestation or given food in accordance to requirements until day 25 and then ad libitum (A) until day 50 or 70. Sows were slaughtered at the Institute's veterinary controlled slaughterhouse at day 50 or 70, respectively. Serum from sows and pools of cord-blood serum from each litter were analysed for glucose, lactate, insulin, insulin-like growth factor (IGF; IGF-1 and -2) and IGF binding proteins (IGFBPs). IGF-1 ( P <0·001) was higher in A compared with C sows, and a 28-kDa IGFBP ( P <0·05) and a 24-kDa IGFBP ( P<0·05) was higher in serum from day 70 compared with day 50 sows. There was no significant effect of food intake on growth factor concentrations in foetal serum or on serum-induced proliferation and differentiation of myoblasts. A 28 kDa IGFBP, IGFBP-2 and -3 were all higher ( P <0·06) and serum-induced proliferation ( P <0·001) and differentiation ( P <0·1) lower at day 70 than day 50. Maternal food intake did not influence the DNA and RNA concentrations and the CPK activity in the foetal longissimus dorsi muscle. The glucose concentration in the liver was higher in C than A foetuses at day 70 of gestation, but not at day 50. In conclusion, no significant effects of maternal nutrition were found on serum growth factor concentrations in the foetuses or on serum-induced proliferation and differentiation of primary myoblasts. [ABSTRACT FROM AUTHOR]

Reverberation mapping takes advantage of the presence of a time delay or lag, τ, between continuum and emission line flux variations observed through spectroscopic monitoring campaigns to infer the radius of the broad-line region (BLR) and, subsequently, the central black hole mass in type 1 AGNs. We present results from a multi-month reverberation mapping campaign undertaken primarily at MDM Observatory with supporting observations from around the world. We measure BLR radii and black hole masses for six objects. The primary goal of this campaign was to obtain either new or improved Hβ reverberation lag measurements for several relatively low-luminosity AGNs. Using cross correlation techniques to measure the time delay between the mean optical continuum flux density around 5100 Å and the integrated Hβ flux, we determine the Hβ lags and black hole mass measurements listed in columns 2 and 3 of Table 1, respectively. Column 4 tells if this measurement is new, an improvement meant to replace a previous, less reliable measurement, or simply an additional measurement not used to replace a previous value. The complete results from this study are currently being prepared for publication. A subsequent velocity-resolved analysis of the Hβ response shows that three of the six primary targets demonstrate kinematic signatures (column 5) of infall, outflow, and non-radial virialized motions (see Denney et al. 2009). [ABSTRACT FROM PUBLISHER]

The objective of the study was to investigate the effect of propylene glycol (PG) allocation on concentrations of milk metabolites with potential use as indicators of glucogenic status in high yielding postpartum dairy cows. At time of calving, nine ruminally cannulated Holstein cows were randomly assigned to ruminal dosing of 500 g/d tap water (CON, n = 4) or 500 g/d PG (PPG, n = 5). The PG was given with the morning feeding week 1-4 postpartum (treatment period) and cows were further followed during week 5-8 postpartum (follow-up period). All cows were fed the same postpartum diet. Milk samples were obtained at each milking (3 times/d) in the treatment period, and at morning milking during the follow-up period. Weekly blood samples were obtained from -4 to +8 weeks relative to calving and daily blood samples from -7 until +7 d relative to calving. The main effect of PG allocation was an increased glucogenic status, e.g. visualised by a prompt marked increase in blood fructosamine. During the treatment period, milk concentration of free glucose tended to be greater, whereas milk concentrations of isocitrate and BHBA were lower for PPG compared with CON. It is proposed that the ratio between free glucose and isocitrate in milk may be a potential biomarker for glucogenic status in the vulnerable early postpartum period. We will pursue this issue in the future.

To evaluate the bioactivity of bovine milk from different stages of lactation on human intestinal tissue, a human fetal small intestinal cell line was used as a model system. Milk samples representing six stages of lactation: days 1, 2-3, 6-7 and weeks 12 and 24 after parturition, 1 week before drying off, and milk-like secretion from two stages of the dry period: 7 weeks and 3-4 weeks before expected calving, were collected from 64 Holstein Friesian cows. The whey fraction of the milk or milk-like secretion was added to the culture medium in concentrations ranging from 0.078% to 10%. The growth-promoting activity of whey was measured by determining the incorporation of [3H]thymidine into DNA for the last 24 h of the culture period. Whey fractions from all six stages of lactation stimulated growth of intestinal cells. The growth-promoting activity of colostrum or milk significantly decreased within the first week after calving. The growth-promoting activity in mature milk increased gradually during lactation to reach a level significantly higher than that obtained with colostrum. The growth-promoting activity of whey from milk-like secretion collected after drying off was lower than that of colostrum. Whey from different stages of lactation contained significantly different concentrations of TGF-beta1 (0.5-27 ng/ml) and TGF-beta2 (12-1219 ng/ml). However, neither the differences in TGF-beta1 and TGF-beta2, nor the differences in IGF-I and IGF-binding proteins could fully explain the differences in growth-promoting activity of colostrums or milk from different stages of lactation, suggesting that other factors were also involved. The present study showed that bovine milk contained a number of biologically active components that affected growth and development of human intestinal tissue. The results showed that the growth-promoting activity of colostrum and milk was dependent on the stage of lactation in accordance with previous results obtained with mammary epithelial cells. The changes in growth-promoting activity with stage of lactation were probably related to changes in concentrations of several growth factors.

Objectives: The purpose of this project was to evaluate local decision support tools used in the Danish hospital sector from a theoretical and an empirical point of view., Methods: The use of local decision support was evaluated through questionnaires sent to all county health directors, all hospital managers, and all heads of clinical departments in cardiology, orthopedic surgery, and intensive care. In addition, respondents were asked to submit whatever decision support tools they were using (including mini-HTAs, other forms or checklists, and special procedures for decision making concerning new health technologies). A theoretical analysis of the decision support tools (decision theory) was performed as well as a comparison with the business case method used in private companies. Finally, the Danish mini-HTA was compared with foreign production and use of HTA and HTA-like assessments as local decision support., Results: The response rate was high (87 percent, 94 percent, 85 percent, respectively). We collected sixty different forms (of which forty-nine were mini-HTAs) and twenty variants of written procedures. We found theoretical and empirical evidence that local involvement in the process of making the HTA could be important for the use of the results from the HTA and for the process of implementing the new technology., Conclusions: Doing mini-HTA in hospitals seems to balance the need for quality and depth with the limited time and resources for assessment.