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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.
OBJECTIVES/SPECIFIC AIMS: To investigate the prognostic value of left ventricular mitral annular longitudinal displacement (LD) measured with color tissue Doppler imaging (TDI) in a large population suffering from acute coronary syndrome (ACS). METHODS/STUDY POPULATION: In total, 501 ACS patients underwent an echocardiography within 9 days after a percutaneous coronary intervention. Regional LD was obtained from the 6 mitral annular regions with TDI and GLD was calculated as an average. RESULTS/ANTICIPATED RESULTS: During a median follow-up time of 4.4 years 46 ACS patients suffered CVD. Mean value of GLD in the population was 8.11mm (±2.4). GLD and LD obtained from the inferior wall remained significant independent predictors after multivariate adjustment for clinical parameters, GLD (HR: 1.43, 95% CI: 1.12–1.82, p=0.014, per 1mm decrease), inferior LD (HR: 1.38, 95% CI: 1.14–1.66, p=0.001). Furthermore, inferior wall LD was the primary source of prognostic information in GLD since only inferior LD remained significant when both measures were included in the same model: GLD (HR: 0.95, 95% CI: 0.64–1.40, p=0.781); inferior LD (HR: 1.60, 95% CI: 1.15–2.22, p=0.005). Of all walls, only inferior wall LD remained as an independent predictor after multivariate adjustment. DISCUSSION/SIGNIFICANCE OF IMPACT: GLD provides independent prognostic information in ACS patients over and beyond all conventional echocardiographic measures. Regional inferior LD was the primary source of prognostic information gained from GLD. GLD proved to be a better predictor of cardiovascular events than conventional echocardiographic measures. This could lead to better risk stratification in the clinical setting and open up for earlier intervention in high-risk individuals.
We present an indentation-scope that interfaces with confocal microscopy, enabling direct observation of the three-dimensional (3D) microstructural response of coatings on substrates. Using this method, we compared microns-thick polymer coatings on glass with and without silica nanoparticle filler. Bulk force data confirmed the >30% modulus difference, while microstructural data further revealed slip at the glass-coating interface. Filled coatings slipped more and about two times faster, as reflected in 3D displacement and von Mises strain fields. Overall, these data indicate that silica-doping of coatings can dramatically alter adhesion. Moreover, this method compliments existing theoretical and modeling approaches for studying indentation in layered systems.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Medulloblastoma and neuroblastoma are aggressive solid pediatric tumors, with 5 year survival rates lower than 50-60%. In addition, more than 80% of the survivors develop permanent neurological impairments. Hence, there is a dire need to identify and validate novel, more effective and less toxic therapeutic approaches. Tumors are continually exposed to acute changes in the micro-environment, including nutrient availability. We previously showed that eukaryotic Elongation Factor-2 Kinase (eEF2K) is a critical regulator of cellular adaptation to acute metabolic stress. Based on those findings, we hypothesize that eEF2K is a marker of outcome and mediates medulloblastoma and neuroblastoma adaptation to acute stress. METHODS – Proprietary gene expression datasets (for medulloblastoma) and the R2 genomic analysis platform (for neuroblastoma) were analyzed for links between eEF2K expression and outcome. Effects of eEF2K knockdown on cell survival were evaluated in BE(2)C neuroblastoma cells. Immunoblotting and immunohistochemistry were performed on neuroblastoma cell lines and tissue microarrays (TMAs) for key molecules in the pathway. Similar studies are underway in medulloblastoma cell lines and TMAs. RESULTS - Low eEF2K mRNA expression is predictive of improved survival in medulloblastoma and neuroblastoma. Low p-eEF2 protein expression, indicative of low eEF2K activity, improves survival in human neuroblastoma. Neuroblastoma cell lines with eEF2K knockdown are more sensitive than controls to nutrient deprivation. CONCLUSIONS - eEF2K may represent a critical mechanism for adaptation to acute metabolic stress in neuroblastoma and medulloblastoma, and is therefore a promising therapeutic target. We are currently exploring the pharmacological inhibition of eEF2K in xenograft tumor models.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Animal slurry is separated in order to avoid excessive nitrogen, phosphorus and potassium (NPK) fertilization of crops in the field. To enhance fertilizer efficiency further, slurry and its separation products may be acidified, for instance in animal houses. The current study quantified the effects of these treatments, both individually and in combination, on fertilizer efficiency, energy production and heavy metal accumulation as a result of manure management. Acidification increased the availability of N to plants in the manure applied, and provided a better match between plant-available NPK in the manure and separation fraction applied to fields and crop need. Total biogas production was not affected by separation, whereas acidification reduced biogas production because the process was inhibited by a low pH and a high sulphur concentration. The amount of copper applied per hectare in the liquid manure to the wheat field was lower than the amount taken up and more zink and copper was applied in the solid fraction to maize field than taken up. The transportation and field application of solids and liquids did not increase management costs when compared to the transportation of slurry alone, but the investment and running costs of separators and manure acidification increased overall management costs.
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.
Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene–environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P = 3.98 × 10−8). We followed up the association in further genotyped monozygotic twins (N = 1,261), which showed a moderate association for the variant (P = 0.200, same direction of an effect). In addition, we report a new association on the level of apolipoprotein A-II (P = 4.03 × 10−8).
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).
Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. However, human studies have suggested that fish consumption has no appreciable association with body-weight gain. We investigated the associations between fish consumption and subsequent change in waist circumference. Sex, age and waist circumference at enrolment were considered as potential effect modifiers. Women and men (n 89 432) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 5·5 years. Mixed-effect linear regression was used to investigate the associations between fish consumption and subsequent change in waist circumference. Among all participants, the average annual change in waist circumference was − 0·01 cm/10 g higher total fish consumption per d (95 % CI − 0·01, 0·00) and − 0·01 cm/10 g higher fatty fish consumption per d (95 % CI − 0·02, − 0·01), after adjustment for potential confounders. Lean fish consumption was not associated with change in waist circumference. Adjustment for potential over- or underestimation of fish consumption measurements did not systematically change the observed associations, but the 95 % CI became slightly wider. The results in subgroups from analyses stratified by sex, age or waist circumference at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption does not prevent increase in waist circumference.
Hospitals play a critical role in communities to provide essential medical care during all types of disaster. Depending on their scope and nature, disasters can lead to rapidly increasing service demand that can overwhelm the functional capacity and safety of hospitals and the health care system at large. The World Health Organization (WHO) Regional Office for Europe All-Hazard Hospital Emergency Preparedness Checklist aims to assist hospital administrators and disaster managers in preparing health facilities to respond effectively to the most likely disaster scenarios.
A checklist tool was developed that comprises current hospital-based emergency management principles and techniques, and integrates applications specific to hospital preparedness needs in the WHO European Region.
A list of recommended actions within critical service categories is provided in a step-wise, all-hazard form for rapid implementation by hospital administrators and disaster managers in response to the most likely types of disaster.
The principles and recommendations provided in this tool may be used by hospitals at any level of emergency preparedness. The checklist is not intended to replace standards and protocols already defined in hospital emergency management plans. Rather, it provides recommendations to enhance existing plans in concert with national guidelines.
A vapor deposition technique has been used to prepare nano-size particles of Fe, Co and Ni using argon gas. The particles were passivated from further oxidation using a small volume of air. The range of particle size obtained in these systems was 47–200 Å. The saturation magnetization of Fe particles varied between 25–200 emu/g with the higher values corresponding to larger particles and the highest coercivity achieved at room temperature was 1050 Oe. In the case of Co and Ni, the magnetization varied in the range 35–100 emu/g and 14–45 emu/g, respectively. The highest room temperature coercivity was 1200 and 41 Oe for Co and Ni, respectively. A shell-type structure consisting of a metallic core surrounded by an oxide shell has been proposed for the particles.
Short duration, incoherent light from a xenon lamp has been used to grow
nickel silicides on silicon single crystals from evaporated nickel films.
The formation of these silicides was studied by Rutherford Backscattering
Spectrometry, channeling, sheet resistivity, and transmission electron
microscopy as function of induced temperature (550– 775°C), exposure time
(8– 25 sec), and silicon orientation (>111<, >110<, and
>100<). Epitaxial NiSi2 films were formed for temperatures
above ˜675°C whereas polycrystalline NiSi films were formed below this
We have demonstrated that gas phase explosive combustion can lead to nanoparticle aerosols with sufficiently large volume fraction to cause a volume spanning gel to form on the order of ten’s of seconds. The term “aerosol gel” was coined to name these materials. So far we have made aerosol gels of carbon and silica. These aerosol gels are similar to well-known, liquid-phase, sol-gel synthesized aerogels.
Sows suffering from clinical signs of disease (e.g. lameness, wounds and shoulder ulcers) are often involuntarily culled, affecting the farmer’s economy and the welfare of the animals. In order to investigate the interrelationships between clinical signs of individual pregnant group-housed sows, we performed an explanatory factor analysis to identify factors describing the patterns of variation of clinical signs. Moreover, we investigated how these emerging factors affected the probability of a sow to be either (i) euthanized, (ii) suddenly dead, (iii) sent to slaughter due to clinical signs of disease such as claw lesions or wounds or (iv) involuntarily culled (representing a pool of sows that were either euthanized, dead or sent to slaughter due to disease). Data from 2.989 pregnant sows in group-housing systems from 33 sow herds were included in the study. A thorough clinical examination was performed for each sow by using a protocol including 16 different clinical signs. Farmers recorded all cullings and deaths and the reasons for these actions in a 3-month period after the clinical examination. Among the observed sows, 4.2% were involuntarily culled during the 3-month period. From the explanatory factor analysis, we identified three factors describing the underlying structure of the 16 clinical variables. We interpreted the factors as ‘pressure marks’, ‘wounds’ and ‘lameness’ Logistic analyses were performed to investigate the effect of the three factors and the parity number of each sow on the four outcomes: (i) euthanized, (ii) suddenly dead, (iii) sent to slaughter due to clinical signs of disease and (iv) involuntarily culled. The analyses showed that ‘lameness’ significantly increased the risk of sows to be involuntarily culled (P = 0.016) or sent to slaughter due to clinical signs of disease (P = 0.026). Lameness is generally considered to be an important welfare problem in sows, which could explain the increased risk seen in this study. By contrast, ‘pressure marks’ and ‘wounds’ did not have any significant effect on the four outcomes (P > 0.05).