Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impacts intrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.

Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.

The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm3/kg, 95% CI:(2.5;13.7 cm3/kg), p = 0.004.

In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

The National Institute of Mental Health's Research Domain Criteria (RDoC) framework has prompted a paradigm shift from categorical psychiatric disorders to considering multiple levels of vulnerability for probabilistic risk of disorder. However, the lack of neurodevelopmentally based tools for clinical decision making has limited the real-world impact of the RDoC. Integration with developmental psychopathology principles and statistical methods actualize the clinical implementation of RDoC to inform neurodevelopmental risk. In this conceptual paper, we introduce the probabilistic mental health risk calculator as an innovation for such translation and lay out a research agenda for generating an RDoC- and developmentally informed paradigm that could be applied to predict a range of developmental psychopathologies from early childhood to young adulthood. We discuss methods that weigh the incremental utility for prediction based on intensity and burden of assessment, the addition of developmental change patterns, considerations for assessing outcomes, and integrative data approaches. Throughout, we illustrate the risk calculator approach with different neurodevelopmental pathways and phenotypes. Finally, we discuss real-world implementation of these methods for improving early identification and prevention of developmental psychopathology. We propose that mental health risk calculators can build a needed bridge between the RDoC multiple units of analysis and developmental science.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Use of antimicrobials for food-producing animals is a major public concern due to the risk of antimicrobial resistance. Although dairy production has a relatively low usage of antimicrobials, the potential for further reduction should be explored. The objective of the study was to estimate the current differences in antimicrobial use in Danish organic and conventional dairy herds and to describe the differences between them. Based on data from three different sources, 2604 herds (306 organic and 2298 conventional) were identified for the study. These herds had been either organic or conventional for the entire period from 2015 to 2018. Antimicrobial use was calculated as the treatment incidence in Animal Daily Doses (ADDs)/100 animals/day for three age groups: adult cattle, young stock and calves. For adult cattle, the ratio of median treatment incidence between conventional and organic production ranged from 2.8 : 1 to 3.4 : 1, depending on the specific year. For cows, 25% of the organic herds had a higher treatment incidence than the 25% of conventional herds with the lowest treatment incidence. Antimicrobial use for young stock was low and at a similar level in both the organic and conventional production systems. For calves, the median treatment incidence was 1.2 times higher in conventional herds and 1.6 times higher for the 75th percentile. Analyses of treatment incidence in adult cattle showed an overall decrease from 2015 to 2018 in both organic and conventional herds. The decrease was greater for the conventional herds (0.12 ADD/100 animals/day) compared to the organic herds (0.04 ADD/100 animals/day) over the 4-year period. In addition, herd size was an important risk factor for treatment incidence in conventional herds, increasing by 0.07 ADD/100 animals/day per 100 cows, whereas herd size had a minor influence on the treatment incidence in organic herds. The results of this study demonstrate the large variation in antimicrobial use within both organic and conventional herds, suggesting that further reduction is possible. Furthermore, herd size appears to be a risk factor in conventional herds but not in organic herds – an aspect that should be studied in more detail.

This paper presents a novel solution for precision draping of prepreg composite fabrics onto double curved molds. Our contributions relate to system design, including hardware and software components, and to system integration. On the hardware side, design and implementation of a drape tool with up to 120 suction cups positioned individually by linear actuators are described. On the software side, design and implementation of the software architecture are presented, along with necessary algorithms within sensor technologies and mathematical modeling. The essential system’s components were verified individually, and the entire integrated system was successfully validated in the Proof-of-Concept experiments, performed on an experimental physical model of the system.

Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (β-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-β-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites’ levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.

Piglet mortality is a major problem in organic pig production affecting both farm economy and animal welfare. Knowledge is scarce on the risk factors of piglet mortality in Danish commercial organic pig production. The objectives of this study were to evaluate season, litter size, parity, sow body condition and stillborn littermates as risk factors for early piglet mortality and crushing of liveborn piglets from parturition until castration at day 3 to 5 postpartum (pp). The study was conducted over a 1-year period in nine commercial Danish organic pig herds practicing outdoor farrowing all year round. Data included recordings on 3393 farrowings with 50 284 liveborn piglets of which 14.8% died before castration. A subset of the dead piglets were collected and necropsied to identify crushed piglets. The average number of liveborn piglets per litter was 14.8 (SD=3.7) and the average time from parturition until castration was 4.1 (SD=1.7) days. A negative binomial regression analysis was used to model the effect of the predictive variables on the early piglet mortality accounting for different time periods from parturition to castration. An increase in maternal body condition score (BCS) and parity significantly increased the risk of dying between parturition and castration. Early mortality was found to be lowest during spring (March to May) and highest during summer (June to August). Being born into a litter with one or more stillborn littermates increased the risk of early mortality. The risk factors for crushing of piglets were evaluated using a logistic analysis. A significant effect of parity and litter size was found where the odds of at least one piglet in a litter with mortality was diagnosed as crushed increased with increasing parity and litter size. In conclusion, being born during summer (June to August), high parity and maternal BCS and stillborn littermates were found to be risk factors for piglet mortality between parturition and castration. In addition, parity and increasing litter size were found to be risk factors for crushing of piglets in litters with mortality.

Managed grasslands are characterized by rotations of leys and arable crops. The regime of water flow evolves during the leys because of earthworm and root activity, climate and agricultural practices (fertilizer, cutting and cattle trampling). The effects of duration of the leys, cattle trampling and fertilizer practice on the movement of water through sandy loam soil profiles were investigated in managed grassland of a dairy operation. Experiments using tracer chemicals were performed, with or without cattle slurry application, with cutting or grazing, in the 1st and the 3rd year of ley, and in winter rye. Each plot was irrigated for an hour with 18·5 mm of water containing a conservative tracer, potassium bromide; 24 h after irrigation, macropores >1 mm were recorded visually on a horizontal plan of 0·7 m2 at five depths (10, 30, 40, 70 and 100 cm). The bromide (Br−) concentration in soil was also analysed at these depths and the density of the different earthworm species were recorded. The density of macropores was not directly influenced by the factors investigated. The abundance of anecic earthworms was larger after 3 years of ley and was not affected by grazing (trampling or dung pat deposits) or fertilizer practice. The water infiltration estimated from the Br− concentration was not influenced by fertilizer practice and was reduced after 3 years of ley due to settlement, but was greater than that for the arable phase of the rotation. As shown by Br− concentration, preferential flow was induced by the grazing regime. Infiltrating water may bypass the soil matrix under similar or more extreme conditions than in the current experiment. Such hydraulic functioning in the grazing regime is expected to reduce the risk of leaching of nitrate contained in soil water.

Glycaemic index (GI) and glycaemic load (GL) are indicators of dietary carbohydrate quantity and quality and have been associated with increased risk of certain cancers and type 2 diabetes. Insulin resistance has been associated with increased melanoma risk. However, GI and GL have not been investigated for melanoma. We present the first study to examine the possible association of GI and GL with melanoma risk. We carried out a population-based, case–control study involving 380 incident cases of cutaneous melanoma and 719 age- and sex-matched controls in a northern Italian region. Dietary GI and GL were computed for each subject using data from a self-administered, semi-quantitative food frequency questionnaire. We computed the odds ratio (OR) for melanoma according to quintiles of distribution of GL and GL among controls. A direct association between melanoma risk and GL emerged in females (OR 2·38; 95 % CI 1·25, 4·52 for the highest v. the lowest quintile of GL score, Pfor trend 0·070) but not in males. The association in females persisted in the multivariable analysis after adjusting for several potential confounders. There was no evidence of an association between GI and melanoma risk. GL might be associated with melanoma risk in females.

In Danish organic pig production, one-third of total born piglets die before weaning, and stillbirth has previously crudely been estimated to account for 27% of the total preweaning mortality. The objective of this study was to evaluate season, litter size, parity and body condition of the sow as risk factors for stillbirth in nine commercial Danish organic pig herds. The study was conducted over a 1-year period, and the data included registrations on 5170 farrowings with 82 906 total born piglets. The average number of total born piglets per litter was 16.0, and the number of stillborn piglets per litter was 1.1. A significant effect of season was seen with an odds ratio for stillbirth of 1.15 during summer (May to August) compared with the remaining part of the year. A non-linear effect of litter size was seen where an increase in litter size from 11 to 16 resulted in an odds ratio of stillbirth of 1.11. An increase in litter size from 16 to 21 resulted in an odds ratio of stillbirth of 1.45. A significant interaction between body condition and parity was present. In first parity sows, an increase in body condition score from 2 (thin) to 3 (moderate) and from 3 to 4 (fat) increased the probability of stillbirth with an odds ratio of 1.23 and 1.36, respectively. In sows with parity above 4, an increase in body condition score from 2 to 3 and from 3 to 4 decreases the probability of stillbirth with an odds ratio of 0.68 and 0.79, respectively. In conclusion, increasing litter size and being born during the summer months of May to August were found to be risk factors for stillbirth. Furthermore, an interaction between body condition and parity showed that thin sows with parity above 4 had a substantially increased risk of stillbirth compared with normal and fat sows with parity above 4. In contrast, for parity 1 sows risk of stillbirth was increased in fat sows.

Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35–74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.

Machery proposes that the construct of “concept” detracts from research progress. However, ignoring development also detracts from research progress. Developmental research has advanced our understanding of how concepts are acquired and thus is essential to a complete theory. We propose a framework that both accounts for development and holds great promise as a new direction for thinking about concepts.

The development of new conjugated-polymer tools for the study of the biological realm, and for use in a clinical setting, is reviewed in this article. Conjugated-polymer actuators, based on the changes of volume of the active conjugated polymer during redox transformation, can be used in electrolytes employed in cell-culture media and in biological fluids such as blood, plasma, and urine. Actuators ranging in size from 10 μm to 100 μm suitable for building structures to manipulate single cells are produced with photolithographic techniques. Larger actuators may be used for the manipulation of blood vessels and biological tissue.