The cellular coding of temperature in the mammalian cortex.

Temperature is a fundamental sensory modality separate from touch, with dedicated receptor channels and primary afferent neurons for cool and warm1-3. Unlike for other modalities, however, the cortical encoding of temperature remains unknown, with very few cortical neurons reported that respond to non-painful temperature, and the presence of a 'thermal cortex' is debated4-8. Here, using widefield and two-photon calcium imaging in the mouse forepaw system, we identify cortical neurons that respond to cooling and/or warming with distinct spatial and temporal response properties. We observed a representation of cool, but not warm, in the primary somatosensory cortex, but cool and warm in the posterior insular cortex (pIC). The representation of thermal information in pIC is robust and somatotopically arranged, and reversible manipulations show a profound impact on thermal perception. Despite being positioned along the same one-dimensional sensory axis, the encoding of cool and that of warm are distinct, both in highly and broadly tuned neurons. Together, our results show that pIC contains the primary cortical representation of skin temperature and may help explain how the thermal system generates sensations of cool and warm.

A dusty compact object bridging galaxies and quasars at cosmic dawn.

Understanding how super-massive black holes form and grow in the early Universe has become a major challenge1,2 since it was discovered that luminous quasars existed only 700 million years after the Big Bang3,4. Simulations indicate an evolutionary sequence of dust-reddened quasars emerging from heavily dust-obscured starbursts that then transition to unobscured luminous quasars by expelling gas and dust5. Although the last phase has been identified out to a redshift of 7.6 (ref. 6), a transitioning quasar has not been found at similar redshifts owing to their faintness at optical and near-infrared wavelengths. Here we report observations of an ultraviolet compact object, GNz7q, associated with a dust-enshrouded starburst at a redshift of 7.1899 ± 0.0005. The host galaxy is more luminous in dust emission than any other known object at this epoch, forming 1,600 solar masses of stars per year within a central radius of 480 parsec. A red point source in the far-ultraviolet is identified in deep, high-resolution imaging and slitless spectroscopy. GNz7q is extremely faint in X-rays, which indicates the emergence of a uniquely ultraviolet compact star-forming region or a Compton-thick super-Eddington black-hole accretion disk at the dusty starburst core. In the latter case, the observed properties are consistent with predictions from cosmological simulations7 and suggest that GNz7q is an antecedent to unobscured luminous quasars at later epochs.

Growth and feed efficiency of Nordic Red Dairy Cattle, Holstein, and their F1 crossbreeds when limiting feed energy concentration in prepubertal heifers.

Milk production and overall dairy farm economics depend on rearing dairy heifers. This study investigated the presence of a genotype by environment interaction in Holstein (HOL), Nordic Red dairy cattle (RDC), and their F1 crossbreeds (HOL × RDC) when provided different feed rations. The aim of our study was to assess how different energy concentrations in feed rations affect growth, BCS, feed intake, and feed efficiency in the 3 groups during the prepubertal period. The 3 breed groups were randomly allocated to receive either a standard or a low-energy feed ration. Holstein heifers exhibited reduced growth and a lower BCS when they were fed the low-energy feed ration. In contrast, the RDC heifers demonstrated similar growth rates with the different feed rations and maintained similar BCS irrespective of feed energy concentration. The HOL × RDC crossbred heifers performed as an intermediate between the HOL and RDC groups. Significant differences were observed in DMI and energy intake in the HOL and HOL × RDC groups depending on feed ration treatment. The RDC heifers had similar feed intake irrespective of treatment. There were no significant differences in the feed conversion ratio among breeds and feed treatments. These results indicate the presence of a genotype by environment interaction in prepubertal HOL and RDC heifers in response to differences in feed ration treatment. Due to the influence of prepubertal growth on future milk production, reproduction, and health status, it is important to be aware of breed-specific requirements during the prepubertal period, particularly in mixed breed and crossbred groups, to optimize growth rates and production potential.

Perceived psychological stress and risk of herpes zoster: a nationwide population-based cohort study.

BACKGROUND: Psychological stress may reduce cellular immunity, but its role in triggering latent infections, including herpes zoster (HZ), is controversial. OBJECTIVES: To examine the association between perceived psychological stress and risk of HZ. METHODS: In a linked registry-based cohort study, we followed 77 310 persons aged 40 years or older who participated in the 2010 Danish National Health Survey from 1 May 2010 until HZ diagnosis, death, emigration or 1 July 2014, whichever occurred first. We computed hazard ratios (HRs) of HZ associated with Cohen's Perceived Stress Scale (PSS) score (range 0-40) using Cox regression with age as the timescale, adjusted for sex, immunosuppressive and selected chronic conditions, immunosuppressive drugs, and sociodemographic, lifestyle and anthropometric factors. The PSS measures chronic stress perceived by an individual in response to various demands of daily life. We modelled the PSS score using quintiles and a restricted cubic spline function. RESULTS: The unadjusted rate of HZ varied from 5·53 to 7·20 per 1000 person-years from the lowest to the highest PSS score quintile. Compared with the lowest PSS score quintile, the adjusted HR for HZ was 1·00 [95% confidence interval (CI) 0·86-1·16], 1·08 (95% CI 0·92-1·26), 1·05 (95% CI 0·90-1·23) and 1·14 (95% CI 0·97-1·34) for the second to the fifth quintile, respectively. In cubic spline analyses, PSS scores < 20 were not associated with increased HR of HZ, but thereafter the HR increased linearly from 1·10 (95% CI 0·85-1·41) to 2·22 (95% CI 1·32-3·75). CONCLUSIONS: Our study indicated that high levels of psychological stress are associated with increased risk of HZ.

Milk supplemented with dried seaweed affects the systemic innate immune response in preweaning dairy calves.

Intact seaweed or seaweed extracts are used as feed supplements to improve the gut microbiome in young animals. Seaweeds provide functional polysaccharides, and they are a good source of vitamins, minerals, and phenolic compounds, all of which are relevant for immune system development. However, literature on the effects of dried seaweed supplementation on immune system development is limited, especially in calves. This experiment aimed to study the effect of feeding milk supplemented with Ulva lactuca, Ascophyllum nodosum, or Saccharina latissima on the systemic immune status of preweaning dairy calves. Forty male Holstein calves with birth body weight 41 ± 4 kg and plasma Brix percentage ≥8.7% at d 2 after birth were used in this study. Calves were fed 4 L of cow milk twice a day (total 8 L/d). From d 2 to d 28, calves in the control group (n = 10) received milk without seaweed supplementation. Over the same period, experimental calves received milk supplemented with Ulva lactuca (SW1; n = 10), Ascophyllum nodosum (SW2; n = 10), or Saccharina latissima (SW3, n = 10). Dried and ground seaweeds were offered at a daily allowance of 50 g/8 L of milk (i.e., approximately 5% inclusion rate on a dry matter basis). Blood samples were collected from a jugular vein on d 2, 4, 7, 14, 21, and 28 after birth. Plasma concentrations of total protein, albumin, immunoglobulins, and acute-phase proteins (i.e., serum amyloid A, fibrinogen, and haptoglobin) were measured. We detected no differences in average daily gain, plasma immunoglobulins, albumin, or total protein. However, the contrast analysis revealed that plasma concentrations of fibrinogen (SW1 and SW2) and serum amyloid A (SW2 and SW3) were significantly higher in the seaweed groups compared with the control group. We also found a tendency for high plasma haptoglobin in the seaweed groups (SW1 and SW2) compared with the control group. Differences in acute-phase protein concentrations could be partially explained by the large differences in micromineral intake between control and seaweed-supplemented calves. Feeding milk supplemented with dried seaweed increased plasma concentrations of variables related to the innate immune response in preweaning dairy calves.

Feeding milk supplemented with Ulva sp., Ascophyllum nodosum, or Saccharina latissima to preweaning dairy calves: Effects on growth, gut microbiota, gut histomorphology, and short-chain fatty acids in digesta.

Emerging knowledge shows the importance of preweaning nutrition on programming the gastrointestinal microbiome and development of the gut barrier function. The aim of this study was to assess the effects of supplementing cow milk with either intact dried Ulva sp., Ascophyllum nodosum, or Saccharina latissima on growth performance and several gut health parameters of preweaning dairy calves. Forty male Holstein calves were selected based on birth weight (41 ± 4 kg) and plasma Brix percentage (≥8.7%) at d 2 of life. From d 2 to d 42 of life, the control calves (n = 10) were fed with cow milk (8 L/d) without seaweed supplementation, and the experimental calves were fed with cow milk (8 L/d) supplemented with either Ulva sp. (n = 10), A. nodosum (n = 10), or S. latissima (n = 10) at a concentration of 50 g/8 L of cow milk per day (i.e., 5% on a dry matter basis). Calves were weighed every week, and body weight gain and calf starter intake were monitored weekly. At d 42 ± 3 of life, calves were slaughtered. The organ weights and digesta pH from the reticulorumen, mid- and end small intestine, and mid-colon were recorded. A tissue sample (5 cm) collected from the mid-small intestine was analyzed for histomorphology. Digesta from the mid-small intestine and mid-colon were analyzed for lactobacilli, Escherichia coli, and Enterobacteriaceae, and short-chain fatty acid profile. Weight gain of the calves was not affected by seaweed supplementation. Proportional organ weights were not affected by seaweed supplementation except for reticulorumen weight, which was higher in calves fed Ulva sp. Both the mid-small intestinal and mid-colonic digesta populations of lactobacilli, Enterobacteriaceae, and E. coli, as well as the mid-small intestinal histomorphology in seaweed-supplemented calves were not different from control calves. However, acetic acid proportion in mid-colonic digesta was increased in calves fed Ulva sp. and A. nodosum, whereas butyric acid proportion was decreased compared with the control calves. Digesta pH in mid- and end small intestine and mid-colon were not affected, whereas ruminal pH was increased in calves fed Ulva sp. compared with the control calves. In conclusion, intact dried seaweed supplementation did not improve the growth or selected gut health parameters (i.e., histomorphology, digesta pH, bacteria, and short-chain fatty acids) in preweaning Holstein calves.

Schizophrenia and attendance in primary healthcare: a population-based matched cohort study.

Objective: Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. The general practitioner (GP) plays a key role in the treatment of mental and physical multimorbidity. Nevertheless, it is unclear how much individuals with schizophrenia use primary healthcare. This study aims to investigate the yearly numbers of consultations in general practice for individuals with schizophrenia. Design and Setting: We performed a population-based matched cohort study of 21,757 individuals with schizophrenia and 435,140 age- and gender-matched references from Danish National Registers. Monthly general practice consultations were analysed using a generalized linear model with log link and assuming negative binomial distribution. Main outcome measures: Consultation rates in general practice up to17 years after index diagnosis. Results: Individuals with schizophrenia attended their GP more than references throughout the study period. The cases had 82% (95% CI: 78-87) and 76% (95% CI: 71-80) more consultations in primary care after 1 year and 5 years, respectively. Individuals with both schizophrenia and comorbid somatic illness attended even more. Conclusion: Individuals with schizophrenia are in regular contact with their GP, especially if they have comorbid illnesses. Whether an average of six consultations per year for individuals with schizophrenia is sufficient is up for debate. The study demonstrates a potential for an increased prevention and treatment of individuals with schizophrenia in general practice. KEY POINTS Schizophrenia is associated with high mortality, somatic comorbidity and reduced life expectancy. Little is known about the attendance pattern in primary care for individuals with schizophrenia. •We found high attendance rates in primary care for individuals diagnosed with schizophrenia from index diagnosis and at least 17 years after diagnosis, which suggests opportunities for earlier intervention to improve their somatic health. •We found an association between high illness comorbidity and increased risk of not attending the general practitioner. The most severely somatically and mentally ill individuals may thus be difficult to reach and support in the current healthcare system.

Bereavement, multimorbidity and mortality: a population-based study using bereavement as an indicator of mental stress.

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.

Performance of Holstein and Swedish-Red × Jersey/Holstein crossbred dairy cows within low- and medium-concentrate grassland-based systems.

This 2 × 2 factorial design experiment was conducted to compare the performance of spring-calving Holstein dairy cows (HOL, n = 34) with Swedish Red × Jersey/Holstein crossbred (SR × J/HOL, n = 34) dairy cows within low and medium concentrate input grassland-based dairy systems. The experiment commenced when cows calved and encompassed 1 full lactation. Cows were offered diets containing grass silage and concentrates [70:30 dry matter (DM) ratio, and 40:60 DM ratio, for low and medium, respectively] until turnout, grazed grass plus either 1.0 or 4.0 kg of concentrate/d during the grazing period (low and medium, respectively), and grass silage and concentrates (85:15 DM ratio, and 70:30 DM ratio, for low and medium, respectively) from rehousing and until drying off. No significant genotype × system interactions were present for any of the feed intake or full-lactation milk production data examined. Full-lactation concentrate DM intakes were 769 and 1,902 kg/cow for the low and medium systems, respectively, whereas HOL cows had a higher total DM intake than SR × J/HOL cows in early lactation, but not in late lactation. Although HOL cows had a higher lactation milk yield than SR × J/HOL cows, the latter produced milk with a higher fat and protein content, and thus fat plus protein yield was unaffected by genotype. Milk produced by the SR × J/HOL cows had a higher degree of saturation of fatty acids than milk produced by the HOL cows, and the somatic cell score of milk produced by the former was also higher. Throughout the lactation, HOL cows were on average 30 kg heavier than SR × J/HOL cows, whereas the SR × J/HOL cows had a higher body condition score than the HOL cows. Holstein cows had a higher incidence of mastitis and ovarian dysfunction that SR × J/HOL cows.

Prenatal maternal bereavement and mortality in the first decades of life: a nationwide cohort study from Denmark and Sweden.

BACKGROUND: The 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. METHOD: The 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. RESULTS: Prenatal 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. CONCLUSION: Prenatal 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.

Risk of stroke after bereavement-a systematic literature review.

Several studies have suggested that psychological stress may increase the risk of stroke. However, this link remains a controversial issue because of conflicting findings. Bereavement, the loss of a close relative, is considered a severely stressful life event. Increased risk of stroke could thus be expected after bereavement if stress plays a causal role. We aimed to evaluate the association between bereavement and stroke by performing a systematic review of the existing literature. The literature search was conducted according to the PRISMA guidelines for systematic reviews. A search in Medline and Embase identified eligible studies, which were reviewed by two researchers independently according to specific inclusion criteria. We included six studies: five cohort studies and one case-crossover study. Five studies found that loss of a first-degree relative was associated with a 1.1- to 2.4-fold higher risk of stroke. However, one study found a statistically significant overall risk only for women. Five studies evaluated the risk of stroke according to time since the loss; one study found no association, two studies indicated short-term effect, one study indicated long-term effect, and one study indicated both short-term and long-term effect. Three studies stratified their analysis by sex; two found higher association in bereaved women than men. Our systematic review suggests that bereavement-related stress is associated with a higher risk of stroke. As relatively few studies were identified, new studies are needed to verify this association. These should aim to quantify the risk, describe the effect of time since bereavement, and identify risk-modifying factors.

Effect of substituting soybean meal and canola cake with dried distillers grains with solubles at 2 dietary crude protein levels on feed intake, milk production, and milk quality in dairy cows.

Dried distillers grain with solubles (DDGS) is an alternative source of feed protein for dairy cows. Previous studies found that DDGS, based on grains other than corn, can substitute for soybean meal and canola cake as a dietary protein source without reducing milk production or quality. As societal concerns exist, and in many areas strict regulation, regarding nitrogen excretion from dairy cows, the dairy industry has focused on reducing dietary protein level and nitrogen excretion. In the present study, we investigated the use of DDGS as a protein source, at a marginally low dietary crude protein (CP) levels, in a grass-clover and corn silage-based ration. The experiment involved 24 Holstein cows and 2 protein sources (DDGS or soybean-canola mixture) fed at 2 levels of CP (14 or 16%) in a 4 × 4 Latin square design. The aim of this study was to evaluate the effect of both protein source and protein level on feed intake, milk yield, and milk quality. The results indicated that feed intake, milk yield, and protein in milk increased when the protein level in the ration was 16% CP compared with 14%. We found no effect of substituting the soybean-canola mixture with DDGS. Moreover, no sensory problems were observed when comparing fresh milk with stored milk, and milk taste was unaffected by DDGS. Milk from cows fed DDGS had a slightly higher content of linoleic acid and conjugated linoleic acid (CLA 9-11), and lower content of C11 to C17 fatty acids than cows fed diets with the soybean-canola mixture. Cows fed the diets with 16% CP produced milk with higher oleic acids and lower palmitic acid content than cows fed 14% CP diets. To conclude, DDGS can substitute for a soybean-canola mixture without affecting feed intake, milk yield and quality, or sensory quality. Under the conditions of this experiment, feeding 16% CP compared with 14% CP in the ration can increase feed intake and milk production.

Effect of substituting soybean meal and canola cake with grain-based dried distillers grains with solubles as a protein source on feed intake, milk production, and milk quality in dairy cows.

The growth of the bioethanol industry is leading to an increase in the production of coproducts such as dried distillers grains with solubles (DDGS). Both corn-based DDGS and grain-based DDGS (gDDGS; defined as originating from grain sources such as barley, wheat, triticale, or a mix, excluding corn) appear to be relevant sources of feed and protein for dairy cows. To date, most of the studies investigating DDGS have been performed with corn-based DDGS. The objectives of this study were to determine the effects of the proportion of gDDGS in the diet on feed intake, milk production, and milk quality. The present experiment involved 48 Holstein cows in a replicated 3 × 3 Latin square design with 3 grass-based dietary treatments consisting of 4, 13.5, and 23% gDDGS on a dry matter (DM) basis (L, M, and H, respectively) as a replacement for a concentrate mix. The concentrate mix consisted of soybean meal, canola cake, and beet pulp. Dry matter intake and energy-corrected milk yield were not affected by the proportion of gDDGS in the diet. Daily milk yield decreased with the H diet compared with the L and M diets. The percentage of fat in milk was higher when cows were fed the H diet compared with the L and M diets, whereas milk fat yield was not affected by dietary treatment. The M diet had a higher percentage of protein in milk compared with the L and H diets. Milk protein yield was similar for the L and M diets; however, it decreased for the H diet. Milk taste was not affected by the proportion of gDDGS in the diet or when milk was stored for 7 d. Linoleic acid and conjugated linoleic acid cis-9,trans-11 in milk increased with increasing proportion of gDDGS. To conclude, gDDGS can replace soybean meal and canola cake as a protein source in the diet of dairy cows. Up to 13.5% of the diet may consist of gDDGS without negatively affecting milk production, milk quality, or milk taste. When gDDGS represents 23% of dietary DM, milk production is reduced by 1.6 kg/d, whereas energy-corrected milk production is numerically reduced by 1 kg.

Maternal bereavement and the risk of preterm delivery: the importance of gestational age and of the precursor of preterm birth.

BACKGROUND: Maternal 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. METHOD: We 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. RESULTS: Overall, 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. CONCLUSIONS: Death 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.

Increased use of primary care during 6 years of prodromal schizophrenia.

BACKGROUND: Early diagnosis is important for the course of schizophrenia. AIM: To investigate whether prodromal symptoms of schizophrenia lead to increased use of primary care. METHOD: A register-based cohort study of 21 894 cases with incident schizophrenia and 437 880 matched controls. RESULTS: Cases used daytime primary care 43% more than controls during the 6 years before diagnosis (IRR = 1.43; 95% CI: 1.39; 1.48) and 132% more during the last 2 months (IRR = 2.32; 95% CI: 2.27; 2.37), and 34% (IRR = 1.34; 95% CI: 1.23; 1.48) vs. 374% more for out-of-hours services (IRR = 3.74; 95% CI: 3.52; 3.98). Six years before index diagnosis, 30% of cases had at least one psychiatric contact without being diagnosed with schizophrenia, increasing to 75% 1 month before diagnosis. CONCLUSION: Increased help-seeking behaviour was seen at least 6 years before index diagnosis, suggesting a 'window' for earlier diagnosis of prodromal schizophrenia.

Milk yield and estrous behavior during eight consecutive estruses in Holstein cows fed standardized or high energy diets and grouped according to live weight changes in early lactation.

Cows managed for extended lactation go through several estruses before rebreeding. The aims of this study were (1) to quantify the effect of the first 8 estruses after calving on milk yield, milking frequency, and estrous behavioral activity, and (2) to determine the effects of early lactation live weight gain (LWG) as an indication of energy balance on milk yield, plasma insulin-like growth factor 1 (IGF-1) concentration, estrous behavioral activity, interval from calving to first estrus, between-estrus intervals, and pregnancy risk. Milk yield, live weight, and estrous behavioral activity were measured daily in 62 Holstein cows, 17 primiparous and 45 multiparous, managed for an 18-mo calving interval. Blood plasma obtained at wk 3, 5, 12, and 24 after calving was analyzed for IGF-1. Estrus was detected by use of milk progesterone profiles combined with visual observations (i.e., mounting behavior and other). The cows were divided into 2 groups: the cows having a negative LWG in each of the first 5 wk postpartum and the cows having a positive LWG in at least 1 of the first 5 wk after calving. The results indicate a similar decrease of 0.56 kg of milk per day of estrus during each of the 8 consecutive estruses. The activity level was 17 ± 1 movements per hour higher during the 8 estruses compared with the basic activity level. More cows expressed mounting behavior at estrus 8 than at estrus 2 (63.3 and 45.9%, respectively). The negative LWG cows had lower IGF-1 and higher milk production than the positive LWG cows. Both LWG groups had similar interval from calving to first estrus, on average 55 d. To conclude, the decrease in milk yield during estrus is marginal and similar in consecutive estruses. Moreover, estrous behavior is more highly expressed in the later estruses compared with the earlier estruses. Reproductive parameters (frequency of mounting, pregnancy risk, interval to first estrus, and between-estrus intervals) were not influenced by the live weight change during early lactation.

Non-participation in breast cancer screening for women with chronic diseases and multimorbidity: a population-based cohort study.

BACKGROUND: Chronic diseases and multimorbidity are common in western countries and associated with increased breast cancer mortality. This study aims to investigate non-participation in breast cancer screening among women with chronic diseases and multimorbidity and the role of time in this association. METHOD: This population-based cohort study used regional and national registries. Women who were invited to the first breast cancer screening round in the Central Denmark Region in 2008-09 were included (n = 149,234). Selected chronic diseases and multimorbidity were assessed up to 10 years before the screening date. Prevalence ratios (PR) were used as an association measure. RESULTS: The results indicated that women with at least one chronic condition were significantly more likely not to participate in breast cancer screening. In adjusted analysis, a significantly higher likelihood of non-participation was found for women with cancer (PR = 1.50, 95% CI: 1.40-1.60), mental illness (PR = 1.51, 95% CI: 1.42-1.60), chronic obstructive pulmonary disease (PR = 1.51, 95% CI: 1.42-1.62), neurological disorders (PR = 1.24, 95% CI: 1.12-1.37) and kidney disease (PR = 1.70, 95% CI 1.49-1.94), whereas women with chronic bowel disease (PR = 0.75, 95% CI 0.65-0.88) were more likely to participate than women without these disease. Multimorbidity was associated with increased non-participation likelihood. E.g. having 3 or more diseases was associated with 58% increased non-participation likelihood (95% CI: 27-96%). Higher non-participation was also observed for women with severe multimorbidity (PR = 1.53, 95% CI: 1.23-1.90) and mental-physical multimorbidity (PR = 1.54, 95% CI: 1.36-1.75). CONCLUSION: In conclusion, we found a strong association between non-participation in breast cancer screening for some chronic diseases and for multimorbidity. The highest propensity not to participate was observed for women with hospital contacts related to the chronic disease in the period closest to the screening date.

Long-term mortality of persons with severe mental illness and diabetes: a population-based cohort study in Denmark.

BACKGROUND: Persons with severe mental illness (SMI) have excess mortality, which may partly be explained by their high prevalence of diabetes. METHOD: We 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. RESULTS: The 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. CONCLUSIONS: Long-term mortality is high for persons with SMI and diabetes. This calls for effective intervention from a coordinated and collaborating healthcare system.

Loss of a close family member the year before or during pregnancy and the risk of placental abruption: a cohort study from Denmark and Sweden.

BACKGROUND: Maternal 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. METHOD: We 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. RESULTS: A 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. CONCLUSIONS: Loss 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.

Preschool behavioral problems in children prenatally exposed to antiepileptic drugs - a follow-up study.

We studied the association between maternal epilepsy, antiepileptic drug (AED) treatment, and behavioral problems in preschool children. In the Danish National Birth Cohort, we identified 4- to 5-year-old children whose mothers had epilepsy and received AED treatment (n=133) or not (n=304) during pregnancy and compared them with randomly selected children whose mothers did not have epilepsy (n=1193). The children's behavioral problems were assessed by the use of the Strengths and Difficulties Questionnaire (SDQ). Children prenatally exposed to AEDs more often had an abnormal total SDQ score as compared with children of women without epilepsy (odds ratio (OR)=4.8 (95% CI: 1.9-12.1)) and as compared with children of women with epilepsy who were not treated with AEDs during their pregnancy (OR=4.0 (95% CI: 1.3-12.8)). In conclusion, prenatal AED exposure may increase the risk of behavioral problems in preschool children even after adjustments for potential confounders and maternal epilepsy.