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Elevated maternal interleukin 6 (IL-6) during pregnancy has been associated with adverse fetal brain development and neurodevelopmental disorders, which often involve executive functioning (EF) impairments. However, the association between maternal IL-6 levels during pregnancy and EF remains largely unexplored.
Methods
The COPSYCH study is based on the prospective COPSAC2010 birth cohort of 700 mother-child pairs, recruited during pregnancy. The children’s executive functioning was assessed at age 10 using: (i) the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) parental questionnaire, and (ii) a comprehensive neuropsychological test battery. Maternal blood levels of IL-6 and hs-CRP were measured at gestational week 24. Associations between IL-6 (main analysis) and hs-CRP (secondary analysis) and EF in children at age 10 were investigated with regression models with extensive confounder adjustment.
Results
Six hundred and four children (86% of the cohort) completed the 10-year follow-up. Higher maternal IL-6 levels were significantly associated with less efficient parental-rated executive functioning in the children: BRIEF-2 Global Executive Composite score (p = 0.003), Behavior Regulation Index (p = 0.005), Emotion Regulation Index (p=0.04), and Cognitive Regulation Index (p=0.007). Interaction analysis with sex was significant (p-value=0.01) and exploratory analyses showed that IL-6 associations to BRIEF-2 were solely driven by boys. Associations between IL-6 and neuropsychological tests, as well as associations between hs-CRP and EF outcomes, were non-significant.
Conclusion
IL-6 during pregnancy was associated with less efficient everyday EF in children at age 10. If replicated, preventive strategies targeting inflammation in pregnancy may ameliorate adverse cognitive outcomes in offspring.
To illustrate that different approaches lead to different costs a cost calculation on four different welfare assessment systems for four different animal species has been carried out; an integrated pig herd (450 sows), a dairy cattle herd with automatic milking (90 cows), an organic egg production system (3000 layers) and a mink farm (1000 mink). We calculated the cost to be: €375 per annum for the mink farm and €2205, €2430 and €2435 for the egg production system, the AMS dairy herd and the integrated pig farm, respectively. The costs can be reduced by: reducing the number of indicators and/or the recording frequency, reducing sample sizes, more intensive use of existing data and by exchanging external for internal recordings.
A welfare indicator protocol integrating a total of 38 measures from 4 information sources: housing system, management, animal behaviour and clinical health has been developed for decision support in Automatic Milking System (AMS) herds. Two expert opinion studies focusing on the relevance of the welfare indicator protocol as basis for on-farm welfare assessment have been carried out; one study focused on the opinion of 21 AMS researchers; the other on that of 14 AMS production advisors and 15 veterinary practitioners. The researchers were asked to score the individual welfare relevance of the 38 measures. Furthermore, both the panels were asked to prioritise the 10 most important measures. The 21 researchers generally appreciated the listed protocol measures as highly relevant. The researcher and advisor panels agreed on prioritised measures from all 4 information sources among the 10 most important welfare indicators. In summary, researchers as well as production advisors and veterinarians supported the suggested measures for inclusion in a welfare assessment system. This has demonstrated that integration of different information is considered decisive for operational welfare assessment at herd level.
This study aimed to identify current weak points in animal welfare in Danish dairy production at herd level using the Welfare Quality® (WQ) protocol, and at national level using the Danish Animal Welfare Index (DAWIN) protocol. The DAWIN was developed as a monitoring tool for the welfare of the Danish dairy cow population, derived from the aggregation of DAWIN assessments at herd level. The DAWIN dairy cow protocol covers 29 measures (13 resource- and 16 animal-based measures) that were weighted and aggregated into a final overall population welfare score. A total of 3,591 cows from 60 dairy herds were assessed throughout 2015. Results from both the WQ and DAWIN were presented at six criteria levels in order to identify specific areas of concern relating to animal welfare at herd versus population level. Both protocols indicated a good general level of welfare across study herds, but also identified insufficient water supply as the main area of concern. In addition, resting comfort (ie time needed to lie down, collisions with barn equipment, cleanliness of rear body parts, animals lying outside of the designated lying area) and disease (in terms of the proportion of cows with chronically elevated somatic cell counts) were identified as problematic areas. The two assessment protocols both identified behavioural deficits, but in the WQ it was due to zero-grazing systems in contrast to the insufficient numbers of cow brushes in the DAWIN protocol. Despite differences in the aggregation, similar areas of concern were identified at criteria level.
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.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
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.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The six LIGO detections of merging black holes (BHs) allowed to infer slow spin values for the two pre-merging BHs. The three cases where the spins of the BHs can be determined in high-mass X-ray binaries (HMXBs) show that those BHs have high spin values. We discuss here scenarios explaining these differences in spin properties in these two classes of object.
Unbalanced metabolic status in the weeks after calving predisposes dairy cows to metabolic and infectious diseases. Blood glucose, IGF-I, non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) are used as indicators of the metabolic status of cows. This work aims to (1) evaluate the potential of milk mid-IR spectra to predict these blood components individually and (2) to evaluate the possibility of predicting the metabolic status of cows based on the clustering of these blood components. Blood samples were collected from 241 Holstein cows on six experimental farms, at days 14 and 35 after calving. Blood samples were analyzed by reference analysis and metabolic status was defined by k-means clustering (k=3) based on the four blood components. Milk mid-IR analyses were undertaken on different instruments and the spectra were harmonized into a common standardized format. Quantitative models predicting blood components were developed using partial least squares regression and discriminant models aiming to differentiate the metabolic status were developed with partial least squares discriminant analysis. Cross-validations were performed for both quantitative and discriminant models using four subsets randomly constituted. Blood glucose, IGF-I, NEFA and BHB were predicted with respective R2 of calibration of 0.55, 0.69, 0.49 and 0.77, and R2 of cross-validation of 0.44, 0.61, 0.39 and 0.70. Although these models were not able to provide precise quantitative values, they allow for screening of individual milk samples for high or low values. The clustering methodology led to the sharing out of the data set into three groups of cows representing healthy, moderately impacted and imbalanced metabolic status. The discriminant models allow to fairly classify the three groups, with a global percentage of correct classification up to 74%. When discriminating the cows with imbalanced metabolic status from cows with healthy and moderately impacted metabolic status, the models were able to distinguish imbalanced group with a global percentage of correct classification up to 92%. The performances were satisfactory considering the variables are not present in milk, and consequently predicted indirectly. This work showed the potential of milk mid-IR analysis to provide new metabolic status indicators based on individual blood components or a combination of these variables into a global status. Models have been developed within a standardized spectral format, and although robustness should preferably be improved with additional data integrating different geographic regions, diets and breeds, they constitute rapid, cost-effective and large-scale tools for management and breeding of dairy cows.
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.
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.
This paper aims to contribute to the development of a cost-effective alternative to expensive on-farm animal-based welfare assessment systems. The objective of the study was to design an animal welfare index based on central database information (DBWI), and to validate it against an animal welfare index based on-farm animal-based measurements (AWI). Data on 63 Danish sow herds with herd-sizes of 80 to 2500 sows and an average herd size of 501 were collected from three central databases containing: Meat inspection data collected at animal level in the abattoir, mortality data at herd level from the rendering plants of DAKA, and medicine records at both herd and animal group level (sow with piglets, weaners or finishers) from the central database Vetstat. Selected measurements taken from these central databases were used to construct the DBWI. The relative welfare impacts of both individual database measurements and the databases overall were assigned in consultation with a panel consisting of 12 experts. The experts were drawn from production advisory activities, animal science and in one case an animal welfare organization. The expert panel weighted each measurement on a scale from 1 (not-important) to 5 (very important). The experts also gave opinions on the relative weightings of measurements for each of the three databases by stating a relative weight of each database in the DBWI. On the basis of this, the aggregated DBWI was normalized. The aggregation of AWI was based on weighted summary of herd prevalence’s of 20 clinical and behavioural measurements originating from a 1 day data collection. AWI did not show linear dependency of DBWI. This suggests that DBWI is not suited to replace an animal welfare index using on-farm animal-based measurements.
Health-beneficial effects of adhering to a healthy Nordic diet index have been suggested. However, it has not been examined to what extent the included dietary components are exclusively related to the Nordic countries or if they are part of other European diets as well, suggesting a broader preventive potential. The present study describes the intake of seven a priori defined healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish and root vegetables) across ten countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) and examines their consumption across Europe.
Design
Cross-sectional study. A 24 h dietary recall was administered through a software program containing country-specific recipes. Sex-specific mean food intake was calculated for each centre/country, as well as percentage of overall food groups consumed as healthy Nordic food items. All analyses were weighted by day and season of data collection.
Setting
Multi-centre, European study.
Subjects
Persons (n 36 970) aged 35–74 years, constituting a random sample of 519 978 EPIC participants.
Results
The highest intakes of the included diet components were: cabbages and berries in Central Europe; apples/pears in Southern Europe; dark bread in Norway, Denmark and Greece; fish in Southern and Northern countries; shellfish in Spain; and root vegetables in Northern and Central Europe. Large inter-centre variation, however, existed in some countries.
Conclusions
Dark bread, root vegetables and fish are strongly related to a Nordic dietary tradition. Apples/pears, berries, cabbages, fish, shellfish and root vegetables are broadly consumed in Europe, and may thus be included in regional public health campaigns.
Experiments were conducted to determine the effectiveness of controlling vortex breakdown in a confined cylindrical vessel using a small rotating disk, which was flush-mounted into the opposite endwall to the rotating endwall driving the primary recirculating flow. The results show that the control disk, with relatively little power input, can modify the azimuthal and axial flow significantly, changing the entire flow structure in the cylinder. Co-rotation was found to precipitate vortex breakdown onset whereas counter-rotation delays it. Furthermore, for the Reynolds-number range over which breakdown normally exists, co-rotation increases the bubble radial and axial dimensions, while shifting the bubble in the upstream direction. By contrast, counter-rotation tends to reduce the size of the bubble, or completely suppress it, while shifting the bubble in the downstream direction. These effects are amplified substantially by the use of larger control disks and higher rotation ratios. A series of numerical simulations close to the onset Reynolds number reveals that the control disk acts to generate a rotation-rate-invariant local positive or negative azimuthal vorticity source away from the immediate vicinity of the control disk but upstream of breakdown. Advection of this source along streamlines modifies the strength of the azimuthal vorticity ring, which effectively controls whether the flow reverses on the axis, and thus, in turn, whether vortex breakdown occurs. The vorticity source generated by the control disk scales approximately linearly with rotation ratio and cubically with disk diameter; this allows the observed variation of the critical Reynolds number to be approximately predicted.
This study assesses the contribution of different sources of human campylobacteriosis in Denmark using two different source-attribution approaches. In total, 794 non-human isolates and 406 isolates from human cases (domestic, travel related, and cases with unknown travel history) were collected. Isolates were characterized by multilocus sequence typing, flaA typing and susceptibility to antibiotics. Both models used indicate that the major burden of human campylobacteriosis in Denmark originates from the domestic broiler chicken reservoir. The second most important reservoir was found to be cattle. The Asymmetric Island model attributed 52% [95% credibility interval (CrI) 37–67] to Danish chicken, 17% (95% CrI 3–33) to imported chicken, and 17% (95% CrI 7–28) to cattle. Similarly, the Campylobacter source-attribution model apportioned 38% (95% CrI 28–47) to Danish chicken, 14% (95% CrI 10–18) to imported chicken, and 16% (95% CrI 7–25) to cattle. The addition of flaA type as an extra discriminatory typing parameter did not change the attribution of cases markedly.
Lameness in sows is an animal welfare problem which also presents an economic challenge to pig producers. Information about the prevalence of herd lameness in organic sows is relatively scarce. The first objective of this study was to establish the prevalence of lameness and to identify risk factors associated with sow lameness in Danish outdoor organic sow herds by analysing the association between risk factors at both sow and herd level using clinical records of lameness. A total of 1850 sows from nine organic herds were included in the study. Second, the study examined differences in the prevalence of sow lameness between outdoor organic and indoor conventional herds. An additional aim here was to identify risk factors associated with clinical records of sow lameness in Danish sow herds by analysing the association between risk factors with lameness at sow and herd level. One thousand and fifty four gestation sows from 44 indoor conventional and nine organic sow herds were included in this study. The nine organic herds were visited twice: once in summer/autumn 2011, and once in winter/spring 2012. In winter/spring 2011, a total of 44 indoor conventional herds were visited. Risk factors included in the study were clinical parameters and factors related to the production system. Sows were examined visually by one of four trained observers. The organic sows were assigned scores for lameness, body condition, hoof length, bursitis, abscesses and leg wounds, while the conventional sows were assigned scores for lameness, body condition and bursitis. A multivariable analysis was carried out by logistic regression with the herd and observer as random effects. The average herd lameness prevalence in gestation and lactation sows in organic herds was 11% in summer/autumn and 4.6% in winter/spring. ‘Wounds, bursitis and abscess’ on legs (OR=4.7, P<0.001) and body condition score >3 (OR=1.79, P=0.008) were associated with increased risk of lameness in Danish organic sow herds. Season (winter/spring v. summer/autumn) lowered the risk of lameness (OR=0.37, P<0.001). Average prevalence of lameness in gestation sow herds in winter/spring in conventional herds was 24.4%, and in organic herds it was 5.4%. An organic sow had a decreased risk of lameness (OR=0.28, P<0.001) as compared with a conventional sow. Bursitis was associated with increased risk of lameness (OR=2.08, P=0.002) regardless of the production system (i.e. whether the herd was organic or conventional).
Neutrinos are one of the major puzzles in modern physics. Despite measurements of mass differences, the Standard Model of particle physics describes them as exactly massless. Additionally, recent measurements from both particle physics experiments and cosmology indicate the existence of more than the three Standard Model species. Here, we review the cosmological evidence and its possible interpretations.
The in utero origins of breast cancer are an increasing focus ofresearch. However, the long time period between exposure and disease diagnosis,and the lack of standardized perinatal data collection makes this researchchallenging. We assessed perinatal factors, as proxies for inutero exposures, and breast cancer risk using pooled,population-based birth and cancer registry data. Birth registries providedinformation on perinatal exposures. Cases were females born in Norway, Sweden orDenmark who were subsequently diagnosed with primary, invasive breast cancer(n = 1419). Ten controls for each case were selected fromthe birth registries matched on country and birth year (n =14,190). Relative risks (RRs) and 95% confidence intervals (CIs) were estimatedusing unconditional regression models. Breast cancer risk rose 7% (95% CI2–13%) with every 500 g (roughly 1 s.d.) increase in birthweight and 7% for every 1 s.d. increase in birth length (95% CI1–14%). The association with birth length was attenuated after adjustmentfor birth weight, while the increase in risk with birth weight remained withadjustment for birth length. Ponderal index and small- andlarge-for-gestational-age status were not better predictors of risk than eitherweight or length alone. Risk was not associated with maternal education or age,gestational duration, delivery type or birth order, or with several pregnancycomplications, including preeclampsia. These data confirm the positiveassociation between birth weight and breast cancer risk. Other pregnancycharacteristics, including complications such as preeclampsia, do not appear tobe involved in later breast carcinogenesis in young women.
This paper shows that control of foodborne disease outbreaks may be challenging even after establishing the source of infection. An outbreak of Salmonella Typhimurium U323 infections occurred in Denmark from March to September 2010, involving 172 cases. Before the detection of human cases, several positive isolates of the outbreak strain had been found in a particular pig slaughterhouse and thus early traceback, investigation and control measures were possible. Several batches of pork and pork products were recalled and the slaughterhouse was closed twice for disinfection. No single common food item was identified as the outbreak source, but repeated isolation of the outbreak strain from the slaughterhouse environment and in pork and products as well as patient interviews strongly suggested different pork products as the source of infection. Furthermore, a matched case-control study identified a specific ready-to-eat spreadable pork sausage (teewurst) as the source of a sub-outbreak (matched odds ratio 17, 95% confidence interval 2·1–130).