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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Fast ice flow is associated with the deformation of subglacial sediment. Seismic shear velocities, Vs, increase with the rigidity of material and hence can be used to distinguish soft sediment from hard bedrock substrates. Depth profiles of Vs can be obtained from inversions of Rayleigh wave dispersion curves, from passive or active-sources, but these can be highly ambiguous and lack depth sensitivity. Our novel Bayesian transdimensional algorithm, MuLTI, circumvents these issues by adding independent depth constraints to the inversion, also allowing comprehensive uncertainty analysis. We apply MuLTI to the inversion of a Rayleigh wave dataset, acquired using active-source (Multichannel Analysis of Surface Waves) techniques, to characterise sediment distribution beneath the frontal margin of Midtdalsbreen, an outlet of Norway's Hardangerjøkulen ice cap. Ice thickness (0–20 m) is constrained using co-located GPR data. Outputs from MuLTI suggest that partly-frozen sediment (Vs 500–1000 m s−1), overlying bedrock (Vs 2000–2500 m s−1), is present in patches with a thickness of ~4 m, although this approaches the resolvable limit of our Rayleigh wave frequencies (14–100 Hz). Uncertainties immediately beneath the glacier bed are <280 m s−1, implying that MuLTI cannot only distinguish bedrock and sediment substrates but does so with an accuracy sufficient for resolving variations in sediment properties.
Ion-implantation has many applications in the fabrication and processing of microelectronic devices from semiconductors, but thermal treatments are required to remove defects produced by the implant and to electrically activate dopants. Recently, pulsed laser annealing has been used to activate surface layers of GaAs that have been heavily doped with 28Si+ by ion implantation, and carrier concentrations of > 1 x 1019 cm-3 have been achieved (Ref. 1). Double-crystal x-ray diffraction techniques are very sensitive to strains and defects in single crystals and provide a means for characterizing and quantifying the damage produced by ion-implantation and the subsequent relief of damage by pulsed laser annealing.
The effects of growing pinto peanut mixed with elephant grass-based pastures are still little known. The aim of the current research was to evaluate the performance of herbage yield, nutritive value of forage and animal responses to levels of pinto peanut forage mass mixed with elephant grass in low-input systems. Three grazing systems were evaluated: (i) elephant grass-based (control); (ii) pinto peanut, low-density forage yield (63 g/kg of dry matter – DM) + elephant grass; and (iii) pinto peanut, high-density dry matter forage yield (206 g/kg DM) + elephant grass. The experimental design was completely randomized with the three treatments (grazing systems) and three replicates (paddocks) in split-plot grazing cycles. Forage samples were collected to evaluate the pasture and animal responses. Leaf blades of elephant grass and the other companion grasses of pinto peanut were collected to analyse the crude protein, in vitro digestible organic matter and total digestible nutrients. The pinto peanut, high-density dry matter forage yield + elephant grass treatment was found to give the best results in terms of herbage yield, forage intake and stocking rate, as well as having higher crude protein contents for both elephant grass and the other grasses, followed by pinto peanut with low-density forage yield + elephant grass and finally elephant grass alone. Better results were found with the grass–legume system for pasture and animal responses.
Multimorbidity is common but little is known about its relationship with obstructive sleep apnea (OSA).
Men Androgen Inflammation Lifestyle Environment and Stress Study participants underwent polysomnography. Chronic diseases (CDs) were determined by biomedical measurement (diabetes, dyslipidaemia, hypertension, obesity), or self-report (depression, asthma, cardiovascular disease, arthritis). Associations between CD count, multimorbidity, apnea-hyponea index (AHI) and OSA severity and quality-of-life (QoL; mental & physical component scores), were determined using multinomial regression analyses, after adjustment for age.
Of the 743 men participating in the study, overall 58% had multimorbidity (2+ CDs), and 52% had OSA (11% severe). About 70% of those with multimorbidity had undiagnosed OSA. Multimorbidity was associated with AHI and undiagnosed OSA. Elevated CD count was associated with higher AHI value and increased OSA severity.
We demonstrate an independent association between the presence of OSA and multimorbidity in this representative sample of community-based men. This effect was strongest in men with moderate to severe OSA and three or more CDs, and appeared to produce a greater reduction in QoL when both conditions were present together.
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.
Cortisol is the primary output of the hypothalamic–pituitary–adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function.
In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80–19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type.
Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone.
Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.
Transfrontier wildlife corridors can be successful conservation tools, connecting protected areas and reducing the impact of habitat fragmentation on mobile species. Urban wildlife corridors have been proposed as a potential mitigation tool to facilitate the passage of elephants through towns without causing conflict with urban communities. However, because such corridors are typically narrow and close to human development, wildlife (particularly large mammals) may be less likely to use them. We used remote-sensor camera traps and global positioning system collars to identify the movement patterns of African elephants Loxondonta africana through narrow, urban corridors in Botswana. The corridors were in three types of human-dominated land-use designations with varying levels of human activity: agricultural, industrial and open-space recreational land. We found that elephants used the corridors within all three land-use designations and we identified, using a model selection approach, that season, time of day and rainfall were important factors in determining the presence of elephants in the corridors. Elephants moved more slowly through the narrow corridors compared with their movement patterns through broader, wide-ranging corridors. Our results indicate that urban wildlife corridors are useful for facilitating elephants to pass through urban areas.
At the meeting of the Commission in 1932 under the Presidency of Prof. E. W. Brown, it was resolved that the “Named Lunar Formations” presented in manuscript by Miss Blagg and Dr Müller should be printed and published. It is anticipated that the volume will be distributed before the meeting of the I.A.U. in Paris.
The reference maps prepared by Mr Wesley and Miss Blagg were not recommended for immediate publication. It was thought that they might be incorporated with the series of photographic maps in preparation by the Committee of the Carnegie Institution of Washington on Study of the Surface Features of the Moon. After correspondence with Dr Wright, however, it seemed better that the maps accompanying the “Named Lunar Formations” should be published with them. The Commission again expresses its great indebtedness to Miss Blagg and Dr Müller for their arduous and painstaking labour.
Flooding of the southern part of the North Sea occurred between 9000 and 8000 BP, when the rate of relative sea-level rise was on the order of 0.7 cm per year for the Dover Strait Region and 1.6 cm per year for the area north of the Frisian Islands, forcing the shoreline to recede rapidly. When relative sea-level rise decelerated after 7000 BP for the Belgian coast and 6000 BP for the central Netherlands coast, sediment supply by the tidal currents balanced the creation of accommodation space in the estuaries and other back-barrier basins. Consequently, the barrier started to stabilize, and the tidal basins and their inlets silted up. Between 5500 and 4500 BP, the Belgian coastal plain changed into a freshwater marsh with peat accumulation, and the same happened 500–1000 years later in the western provinces of the Netherlands. The E-W running barrier/back-barrier system of the Frisian Islands in the northern Netherlands stayed open until today, however, because of lower sediment supply.
The period between 4000 and 2000 BP was relatively quiet due to the strong deceleration of the rate of sea-level rise; peat cushions developed behind the barriers, which were straightened by erosion of the headlands. Major and often catastrophic flooding occurred in the Middle Ages, when the estuaries in the southwestern part of the Netherlands formed.
About 226 (± 15%) × 109 m3 sediment, mostly sand, is stored in the barriers and back-barrier basins of the Netherlands, 70% of which was deposited prior to 5000 BP. About 10% of the stored sediment is estimated to be of alluvial origin. Most of the sediment is derived by the erosion of the Pleistocene basement during recession of the barriers, but tide-induced crossshore transport from the North Sea forms an additional source for the barriers and back-barriers of the west-facing coast of the Netherlands.
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.
We present a tapped tunable delay line filter for radiofrequency (RF) photonic filtering applications, capable of rapid tunability over a wide RF bandwidth limited only by the optical components’ losses, while maintaining independence from polarization state. Multiple fiber taps with contrasting dispersion slopes are used in intensity-modulated direct detection microwave photonic links. A temporal delay is generated between the signals within each arm of the link. Once a signal is received using balanced differential detection, nulls are generated as a function of the laser's operating wavelength. Tuning of the laser allows for a rapid shifting of the nulls in the RF spectrum to dynamically mitigate co-site interference. Through this method we demonstrate the potential for rapid tunability over the RF spectrum by the variation of the operating wavelength of the optical carrier.
Depression is characterized by poor executive function, but – counterintuitively – in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study.
One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials).
Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = −0.28, p = 0.007).
Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.