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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.
Although application of organic fertilizers has become a recommended way for developing sustainable agriculture, it is still unclear whether above-ground and below-ground crops have similar responses to chemical fertilizers (CF) and organic manure (OM) under the same farming conditions. The current study investigated soil quality and crop yield response to fertilization of a double-cropping system with rapeseed (above-ground) and sweet potato (below-ground) in an infertile red soil for 2 years (2014–16). Three fertilizer treatments were compared, including CF, OM and organic manure plus chemical fertilizer (MCF). Organic fertilizers (OM and MCF) increased the yield of both above- and below-ground crops and improved soil biochemical properties significantly. The current study also found that soil-chemical properties were the most important and direct factors in increasing crop yields. Also, crop yield was affected indirectly by soil-biological properties, because no significant effects of soil-biological activities on yield were detected after controlling the positive effects of soil-chemical properties. Since organic fertilizers could not only increase crop yield, but also improve soil nutrients and microbial activities efficiently and continuously, OM application is a reliable agricultural practice for both above- and below-ground crops in the red soils of China.
Introduction: ex-specific diagnostic cutoffs may improve the test characteristics of high-sensitivity troponin assays for the diagnosis of myocardial infarction. Sex-specific cutoffs for ruling in MI improve the sensitivity of the assay for MI among women, and improve the specificity of diagnosis among men. We hypothesized that the use of sex-specific high-sensitivity Troponin T (hsTnT) cutoffs for ruling out MI at the time of ED arrival would improve the classification efficiency of the assay by enabling more patients to have MI ruled out at the time of ED arrival while maintaining diagnostic sensitivity. The objective of this study was to quantify the test characteristics of sex-specific cutoffs of an hsTnT assay for acute myocardial infarction (AMI) when performed at ED arrival in patients with chest pain. Methods: This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs were, excluding those with ST-elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes was AMI at 7 days. Secondary outcomes included major adverse cardiac events (MACE: all-cause mortality, AMI and revascularization) and the individual MACE components. We quantified test characteristics (sensitivity, negative predictive value, likelihood ratios and proportion of patients ruled out) for multiple combinations of sex-specific rule-out cutoffs. We calculated net reclassification improvement compared to universal rule-out cutoffs of 5ng/L (the assays limit of detection) and 6ng/L (the FDA-approved limit of quantitation for US laboratories). Results: 7130 patients, including 3931 men and 3199 women, were included. The 7-day incidence of AMI was 7.38% among men and 3.78% among women. Universal cutoffs of 5 and 6 ng/L ruled out AMI with 99.7% sensitivity in 33.6 and 42.2% of patients. The best-performing combination of sex-specific cutoffs (8g/L for men and 6ng/L for men) ruled out AMI with 98.7% sensitivity in 51.9% of patients. Conclusion: Sex-specific hsTnT cutoffs for ruling out AMI at ED arrival may achieve substantial improvement in classification performance, enabling more patients to be ruled out at ED arrival, while maintaining acceptable diagnostic sensitivity for AMI. Universal and sex-specific rule-out cutoffs differ by only small changes in hsTnT concentration. Therefore, these findings should be confirmed in other datasets.
Introduction: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular events, and have worse outcomes following acute myocardial infarction (AMI). Cardiac troponin is often elevated in CKD, making the diagnosis of AMI challenging in this population. We sought to quantify test characteristics for AMI of a high-sensitivity troponin T (hsTnT) assay performed at emergency department (ED) arrival in CKD patients with chest pain, and to derive rule-out cutoffs specific to patient subgroups stratified by estimated glomerular filtration rate (eGFR). We also quantified the sensitivity and classification performance of the assays limit of detection (5 ng/L) and the FDA-approved limit of quantitation (6 ng/L) for ruling out AMI at ED arrival. Methods: Consecutive patients in four urban EDs from the 2013 calendar year with suspected cardiac chest pain who had a Roche Elecsys hsTnT assay performed on arrival were included f. This analysis was restricted to patients with an eGFR< 60 ml/min/1.73m2. The primary outcome was 7-day AMI. Secondary outcomes included major adverse cardiac events (death, AMI and revascularization). Test characteristics were calculated and ROC curves were generated for eGFR subgroups. Results: 1416 patients were included. 7-day AMI incidence was 10.1%. 73% of patients had an initial hsTnT concentration greater than the assays 99th percentile (14 ng/L). TCurrently accepted cutoffs to rule out MI at ED arrival ( 5 ng/L and 6 ng/L) had 100% sensitivity for AMI, but no patients with an eGFR less than 30 ml/min/1.73M had hsTnT concentrations below these thresholds. We derived eGFR-adjusted cutoffs to rule out MI with sensitivity >98% at ED arrival, which were able to rule out 6-42% of patients, depending on eGFR category. The proportion of patients able to be accurately ruled-in with a single hsTnT assay was substantially lower among patients with an eGFR <30 ml/min/1.73m2 (6-20% vs 25-43%). We also derived eGFR-adjusted cutoffs to rule-in AMI with specificity >90%, which accurately ruled-in up to 18% of patients. Conclusion: Cutoffs achieving acceptable diagnostic performance for AMI using single hsTnT sampling on ED arrival may have limited clinical utility, particularly among patients with very low eGFR. The ideal diagnostic strategy for AMI in patients with CKD likely involves serial high-sensitivity troponin testing with diagnostic thresholds customized to different eGFR categories.
The submarine channel-fill system of the Cambrian Spurs Formation exhibits unique metre-scale cycles of breccia and diamictite. The studied sections, Eureka Spurs, are located at the Mariner Glacier in the central-eastern part of northern Victoria Land, Antarctica. A facies analysis of the channel-fill deposit has led to the recognition of four main lithofacies: breccia, diamictite, thin-bedded sandstone and mudstone. The channel-fill deposit consists of two architectural elements: hollow-fill (HF) and sheet-like (SL) elements. The SL has wide convex-up geometry and consists solely of a very thick bed of diamictite, and is interpreted as a submarine channel lobe. The HF has a concave-up erosional base and flat upper surface. The HF consists of nine cyclic alternations of underlying breccia (cohesionless debris flow) and overlying diamictite (cohesive debris flow). The deposition of breccia is interpreted to have been controlled by repeated allogenic processes such as earthquakes. In contrast, the abrupt vertical transition from breccia to diamictite in each cycle is interpreted to have resulted from an autogenic, slope instability-related process. The interaction of the allogenic and autogenic factors recorded in the metre-scale unique cyclic deposits provides new criteria to interpret cycles of submarine debris flow.
In this work we consider the generalized Pólya process with baseline intensity function r and parameters α and β recently studied by Cha (2014). The aim of this work is to provide both univariate and multivariate stochastic comparisons between two generalized Pólya processes with different baseline intensity functions and the same parameters α and β for the epoch and inter-epoch times of the two processes. The comparisons are analogous to stochastic comparisons in Belzunce et al. (2001) for two nonhomogeneous Poisson or pure-birth processes with different intensity functions. Moreover, we study both univariate and multivariate ageing properties of the epoch and inter-epoch times of the generalized Pólya process.
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.
Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.
We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.
ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.
Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
This paper critically evaluates methods used to synthesize boride compounds with emphasis on diborides of the early transition metals. The earliest reports of the synthesis of boride ceramics used impure elemental powders to produce multiphase reaction products; phase-pure borides were only synthesized after processes were established to purify elemental boron. Carbothermal reduction of the corresponding transition metal oxides emerged as a viable production route and continues to be the primary method for the synthesis of commercial transition metal diboride powders. Even though reaction-based processes and chemical synthesis methods are mainly used for research studies, they are powerful tools for producing diborides because they provide the ability to tailor purity and particle size. The choice of synthesis method requires balancing factors that include cost, purity, and particle size with the performance needed in expected applications.
Introduction: Chest pain and symptoms of acute coronary syndrome are responsible for a large proportion of ED visits and acute hospitalizations. However, only about 15% of patients presenting to the ED with high-risk symptoms do, in fact, have an acute coronary syndrome. The objective of this study is to derive a 2-hour high-sensitivity Troponin T (hsTnT) testing algorithm with outcome based-cutoffs to rapidly rule out acute myocardial infarction (AMI) in a large proportion of ED chest pain patients. Methods: Patients included consecutive ED patients with a chief complaint of cardiac chest pain who had an hsTnT assay performed at ED arrival and 2 hours after ED arrival. Administrative databases were queried to identify troponin results and major adverse cardiac outcomes (MACE) including death, MI, and revascularization. Test characteristics of iterative combinations of initial troponin level and absolute change in troponin level were quantified in order to identify the testing algorithm that identified the greatest proportion of patients eligible for early discharge while maintaining a target sensitivity of 98.5% for the primary outcome of 7-day AMI. Results: 755 eligible patients had hsTnT assays performed at ED arrival and at 2 hours. 91 patients (12.1%) had a 7-day AMI while 108 (14.0%) had 7-day MACE. An initial hsTnT level of less than 14 ng/L, in combination with a 2-hour absolute change of less than 10ng/L had a sensitivity of 98.9% (95% CI 94.0,99.8) and an NPV of 99.8% (95% CI 98.7, 100.0) for 7-day AMI. This identified 58.5% of all patients as being suitable for early discharge. Sensitivity and NPV for 7-day MACE were 90.0% (95% CI 83.3, 94.2) and 97.3% (95% CI 95.3,98.4) respectively. Sex-specific differences in test characteristics were not clinically important. Rule-in hsTnT cutoffs were also evaluated, with specificities ranging from 85-95%, although cutoffs with higher specificity had less ability to rapidly rule-in AMI, leaving more patients with indeterminate results after 2 hours. Conclusion: A hsTnT algorithm can safely and accurately rule out AMI in 58.5% of ED chest pain patients within 2 hours of ED arrival. The lower sensitivity of this algorithm for MACE compared to AMI speaks to the importance of clinical assessment and ECG findings in identifying patients at risk for acute coronary syndromes.
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.
The intracavity optogalvanic spectroscopy (ICOGS) method has been reported to quantify radiocarbon at subambient levels (<1 part per trillion). ICOGS uses a gas sample that is ionized in a low-pressure glow discharge located inside a 14CO2 laser cavity to detect changes in the discharge current under periodic modulation of the laser power to determine the 14CO2 concentration of the sample. When claims of detection thresholds below ambient levels were not verified by other researchers, we constructed a theoretical analysis to resolve differences between these conflicting reports and built and tested an ICOGS system to establish a lower limit of detection. Using a linear absorbance model of the background contribution of 12CO2 and data from the HITRAN database, we estimate that the limit of detection (3σx) is close to 1.5×104 Modern. By measuring a 1.5×104 Modern enriched CO2 sample in a cavity modulation ICOGS system without a clear signal, we conclude that for this system the limit of detection for ICOGS must be above 1.5×104. The implications for previous ICOGS reports are discussed.
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.
Since the electromagnetic energy gained by the laser wave in a free-electron laser (FEL) is transferred from the kinetic energy loss of a relativistic electron beam, the stability of electron motion is one of the key factors that affect FEL performance. In this paper the stability of electron motion is compared for different focusing regimes. It is demonstrated that the natural focusing regime of a three-dimensional wiggler is easily broken by the self-field of the electron beam. The magnetic focusing regime of an axial guide magnetic field is based on the superposition of a strong Larmor rotation on the transverse quiver motion of the electrons, while the electric focusing regime of an ion-channel guiding field generates an electric force to counteract the divergent effect of the beam self-field. In comparison with the magnetic focusing regime of an external magnetic system, the electric focusing regime of an ion-channel guiding field may yield smaller instantaneous Larmor radius and slighter Larmor-centre deviation from the axis and provide better motion stability.
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.
Electroretinogram (ERG) studies identified a new mouse line with a normal a-wave
but lacking the b-wave component. The ERG phenotype of this new allele,
nob7, matched closely that of mouse mutants for
Grm6, Lrit3, Trpm1, and
Nyx, which encode for proteins expressed in depolarizing
bipolar cells (DBCs). To identify the underlying mutation, we first crossed
nob7 mice with Grm6nob3 mutants and measured the ERGs in offspring. All the offspring lacked the
b-wave, indicating that nob7 is a new allele for
Grm6: Grm6nob7. Sequence analyses of Grm6nob7 cDNAs identified a 28 base pair insertion between exons 8 and 9, which
would result in a frameshift mutation in the open reading frame that encodes the
metabotropic glutamate receptor 6 (Grm6). Sequencing both the
cDNA and genomic DNA from exon 8 and intron 8, respectively, from the
Grm6nob7 mouse revealed a G to A transition at the last position in exon 8. This
mutation disrupts splicing and the normal exon 8 is extended by 28 base pairs,
because splicing occurs 28 base pairs downstream at a cryptic splice donor.
Consistent with the impact of the resulting frameshift mutation, there is a loss
of mGluR6 protein (encoded by Grm6) from the dendritic tips of
DBCs in the Grm6nob7 retina. These results indicate that Grm6nob7 is a new model of the complete form of congenital stationary night
blindness, a human condition that has been linked to mutations of
Saturation-power enhancement of a free-electron laser (FEL) amplifier by using tapered wiggler amplitude is based on the postponement of the saturation length of the uniform wiggler. In this paper, we qualitatively and quantitatively demonstrate that the saturation-power enhancement can be approached by means of the parameters adjustment, which is comparable to that by using a tapered wiggler. Compared to the method by tapering the wiggler amplitude, the method of parameters adjustment substantially shortens the saturation length, which is favorable to cutting down the manufacture and operation costs of the device.
Human infection with the emerging avian influenza A(H7N9) virus in China in 2013 has raised global concerns. We conducted a retrospective descriptive study of 27 confirmed human influenza A(H7N9) cases in Jiangsu Province, to elaborate poultry-related exposures and to provide a more precise estimate of the incubation periods of the illness. The median incubation period was 6 days (range 2–10 days) in cases with single known exposure and was 7·5 days (range 6·5–12·5 days) in cases with exposures on multiple days, difference between the two groups was not significant (Z = −1·895, P = 0·058). The overall median incubation period for all patients was estimated to be 7·5 days (range 2–12·5 days). Our findings further highlight the necessity for public health authorities to extend the period of medical surveillance from 7 days to 10 days.