Irish study on high-density schizophrenia families:field methods and power to detect linkage

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one whom had schizophrenia (S) or poor-outcome schizo-affective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. The phenotypic sample contained 277 pedigrees and 1,770 individuals and the linkage sample 265 pedigrees and 1,408 individuals. Using the intermediate definition of affection, the phenotypic sample contained 837 affected individuals and 526 affected sibling pairs. Parallel figures for the linkage sample were 700 and 420. Individuals with schizophrenia from these multiplex pedigrees resembled epidemiologically sampled cases with respect to age at onset, gender distribution, and most clinical symptoms, although they were more thought-disordered and had a poorer outcome. Power analyses based on the model of linkage heterogeneity indicated that the ISHDSF should be able to detect a major locus that influences susceptibility to schizophrenia in as few as 20% of families. Compared to first-degree relatives of epidemiologically sampled schizophrenic probands, first-degree relatives of schizophrenic members from the ISHDSF had a similar risk for schizotypal personality disorder, affective illness, alcoholism, and anxiety disorder. With sufficient resources, large-scale ascertainment of multiplex schizophrenia pedigrees is feasible, especially in countries with catchmented psychiatric care and stable populations. Although somewhat more severely ill, schizophrenic members of such pedigrees appear to clinically resemble typical schizophrenic patients. Our ascertainment process for multiplex schizophrenia families did not select for excess familial risk for affective illness or alcoholism. With its large sample ascertained in a standardized manner from a relatively homogeneous population, the ISHDSF provides considerable power to detect susceptibility loci for schizophrenia.

Resemblance of psychotic symptoms and syndromes in affected sibling pairs from the Irish Study of High-Density Schizophrenia Families:evidence for possible etiologic heterogeneity

The authors sought to determine whether the clinical manifestations of schizophrenia and other psychotic disorders are correlated in affected sibling pairs.

Sibling correlation of deficit syndrome in the Irish study of high-density schizophrenia families

The deficit syndrome is a subtype of schizophrenia characterized by primary and enduring negative features of psychopathology. It appears to reflect a distinct subtype within the syndrome of schizophrenia. Little is known about the familial or genetic aspects of the deficit syndrome. The purpose of this study was to determine whether deficit versus nondeficit subtypes are correlated in sibling pairs affected with schizophrenia.

Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families

The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.

No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

Analysis of the compressive behaviour of the three-dimensional printed porous titanium for dental implants using a modified cellular solid model

A set of cylindrical porous titanium test samples were produced using the three-dimensional printing and sintering method with samples sintered at 900 °C, 1000 °C, 1100 °C, 1200 °C or 1300 °C. Following compression testing, it was apparent that the stress-strain curves were similar in shape to the curves that represent cellular solids. This is despite a relative density twice as high as what is considered the threshold for defining a cellular solid. As final sintering temperature increased, the compressive behaviour developed from being elastic-brittle to elastic-plastic and while Young's modulus remained fairly constant in the region of 1.5 GPa, there was a corresponding increase in 0.2% proof stress of approximately 40-80 MPa. The cellular solid model consists of two equations that predict Young's modulus and yield or proof stress. By fitting to experimental data and consideration of porous morphology, appropriate changes to the geometry constants allow modification of the current models to predict with better accuracy the behaviour of porous materials with higher relative densities (lower porosity).

Seasonality of cardiovascular risk factors: an analysis including over 230 000 participants in 15 countries

Objective: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies.

Methods: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed.

Results: In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m2 for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol.

Conclusions: CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.

Spatial and Temporal Changes in Soil Organic Carbon Assessment using an Integrated Geostatistical and Compositional Data Analysis Approach

The Irish and UK governments, along with other countries, have made a commitment to limit the concentrations of greenhouse gases in the atmosphere by reducing emissions from the burning of fossil fuels. This can be achieved (in part) through increasing the sequestration of CO2 from the atmosphere including monitoring the amount stored in vegetation and soils. A large proportion of soil carbon is held within peat due to the relatively high carbon density of peat and organic-rich soils. This is particularly important for a country such as Ireland, where some 16% of the land surface is covered by peat. For Northern Ireland, it has been estimated that the total amount of carbon stored in vegetation is 4.4Mt compared to 386Mt stored within peat and soils. As a result it has become increasingly important to measure and monitor changes in stores of carbon in soils. The conservation and restoration of peat covered areas, although ongoing for many years, has become increasingly important. This is summed up in current EU policy outlined by the European Commission (2012) which seeks to assess the relative contributions of the different inputs and outputs of organic carbon and organic matter to and from soil. Results are presented from the EU-funded Tellus Border Soil Carbon Project (2011 to 2013) which aimed to improve current estimates of carbon in soil and peat across Northern Ireland and the bordering counties of the Republic of Ireland.
Historical reports and previous surveys provide baseline data. To monitor change in peat depth and soil organic carbon, these historical data are integrated with more recently acquired airborne geophysical (radiometric) data and ground-based geochemical data generated by two surveys, the Tellus Project (2004-2007: covering Northern Ireland) and the EU-funded Tellus Border project (2011-2013) covering the six bordering counties of the Republic of Ireland, Donegal, Sligo, Leitrim, Cavan, Monaghan and Louth. The concept being applied is that saturated organic-rich soil and peat attenuate gamma-radiation from underlying soils and rocks. This research uses the degree of spatial correlation (coregionalization) between peat depth, soil organic carbon (SOC) and the attenuation of the radiometric signal to update a limited sampling regime of ground-based measurements with remotely acquired data. To comply with the compositional nature of the SOC data (perturbations of loss on ignition [LOI] data), a compositional data analysis approach is investigated. Contemporaneous ground-based measurements allow corroboration for the updated mapped outputs. This provides a methodology that can be used to improve estimates of soil carbon with minimal impact to sensitive habitats (like peat bogs), but with maximum output of data and knowledge.

Fruit and vegetable consumption and muscle strength and power during adolescence: a cross-sectional analysis of the Northern Ireland Young Hearts Project 1999-2001

Objectives: To examine the association between fruit and vegetable (FV) consumption and muscle strength and power in an adolescent population. Methods: We conducted a cross-sectional analysis among 1019 boys and 998 girls, aged 12 and 15 years, who participated in The Young Hearts Project. FV consumption (excluding potatoes) was assessed by 7-d diet history. Grip strength and jump power was assessed with a dynamometer and Jump-MD meter, respectively. Associations between FV consumption and strength and power were assessed by regression modelling. Results: Boys and girls with the highest FV intakes (>237.71 g/d and >267.57 g/d, respectively, based on the highest tertile) had significantly higher jump power than those with the lowest intakes (<135.09 g/d and <147.43 g/d, respectively), after adjustment for confounding factors. Although girls with the highest FV intakes had higher grip strength than those with the lowest intakes, no significant independent associations were evident between FV intake and grip strength in boys or girls. Similar findings were observed when FV were analysed separately.Conclusions: Higher FV consumption in this group of adolescents was positively associated with muscle power. There was no independent association between higher FV consumption and muscle strength. Intervention studies are required to determine whether muscle strength and power can be improved through increased FV consumption.

Stochastic Analysis of Saltwater Intrusion in Heterogeneous Aquifers using Local Average Subdivision

This study investigates the effects of ground heterogeneity, considering permeability as a random variable, on an intruding SW wedge using Monte Carlo simulations. Random permeability fields were generated, using the method of Local Average Subdivision (LAS), based on a lognormal probability density function. The LAS method allows the creation of spatially correlated random fields, generated using coefficients of variation (COV) and horizontal and vertical scales of fluctuation (SOF). The numerical modelling code SUTRA was employed to solve the coupled flow and transport problem. The well-defined 2D dispersive Henry problem was used as the test case for the method. The intruding SW wedge is defined by two key parameters, the toe penetration length (TL) and the width of mixing zone (WMZ). These parameters were compared to the results of a homogeneous case simulated using effective permeability values. The simulation results revealed: (1) an increase in COV resulted in a seaward movement of TL; (2) the WMZ extended with increasing COV; (3) a general increase in horizontal and vertical SOF produced a seaward movement of TL, with the WMZ increasing slightly; (4) as the anisotropic ratio increased the TL intruded further inland and the WMZ reduced in size. The results show that for large values of COV, effective permeability parameters are inadequate at reproducing the effects of heterogeneity on SW intrusion.

Density functional study of the C atom adsorption on the α-Fe 2O3 (001) surface

The adsorption of C atoms on the α-Fe₂O₃ (001) surface was studied based on density function theory (DFT), in which the exchange-correlation potential was chosen as the PBE (Perdew, Burke and Ernzerhof) generalized gradient approximation (GGA) with a plane wave basis set. Upon the optimization on different adsorption sites with coverage of 1/20 and 1/5 ML, it was found that the adsorption of C atoms on the α-Fe ₂O₃ (001) surface was chemical adsorption. The coverage can affect the adsorption behavior greatly. Under low coverage, the most stable adsorption geometry lied on the bridged site with the adsorption energy of about 3.22 eV; however, under high coverage, it located at the top site with the energy change of 8.79 eV. Strong chemical reaction has occurred between the C and O atoms at this site. The density of states and population analysis showed that the s, p orbitals of C and p orbital of O give the most contribution to the adsorption bonding. During the adsorption process, O atom shares the electrons with C, and C can only affect the outermost and subsurface layers of α-Fe₂O₃; the third layer can not be affected obviously. Copyright © 2008 Chinese Journal of Structural Chemistry.

Effective grain size distribution analysis for interpretation of tidal-deltaic facies: West Bengal Sundarbans

Research over the past two decades on the Holocene sediments from the tide dominated west side of the lower Ganges delta has focussed on constraining the sedimentary environment through grain size distributions (GSD). GSD has traditionally been assessed through the use of probability density function (PDF) methods (e.g. log-normal, log skew-Laplace functions), but these approaches do not acknowledge the compositional nature of the data, which may compromise outcomes in lithofacies interpretations. The use of PDF approaches in GSD analysis poses a series of challenges for the development of lithofacies models, such as equifinal distribution coefficients and obscuring the empirical data variability. In this study a methodological framework for characterising GSD is presented through compositional data analysis (CODA) plus a multivariate statistical framework. This provides a statistically robust analysis of the fine tidal estuary sediments from the West Bengal Sundarbans, relative to alternative PDF approaches.

A cross-sectional study demonstrating increased serum amyloid A-related inflammation in high density lipoproteins from subjects with type 1 diabetes mellitus and how this association was augmented by poor glycaemic control

Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins(HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this propertymay be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matchedcontrol subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-,and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly inserum (P = 0.088), and significantly in HDL2 (P  = 0.003) and HDL3 (P  = 0.005). When the T1DM group were separated accordingto mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared towhen HbA1c was <8.34% (P  < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAAincreased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P  > 0.05).This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poorglycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increasedatherosclerosis risk.

Conjugate Heat Transfer Analysis of an Internally Cooled Gas Turbine Vane

A conjugate heat transfer (CHT) method was used to perform the aerothermal analysis of an internally cooled turbine vane, and was validated against experimental and empirical data.
Firstly, validation of the method with regard to internal cooling was done by reproducing heat transfer test data in a channel with pin fin heat augmenters, under steady constant wall temperature. The computed Nusselt numbers for the two tested configurations (full length circular pin fins attached to both walls and partial pin fins attached to one wall only) showed good agreement with the measurements. Sensitivity to mesh density was evaluated under this simplified case in order to establish mesh requirements for the analysis of the full component.
Secondly, the CHT method was applied onto a turbine vane test case from an actual engine. The predicted vane airfoil metal temperature was compared to the measured thermal paint data and the in-house empirical predictions. The CHT results agreed well with the thermal paint data and showed better prediction than the current empirical modeling approach.

Design and Analysis of Inexact Floating-Point Adders

Power has become a key constraint in nanoscale inte-grated circuit design due to the increasing demands for mobile computing and higher integration density. As an emerging compu-tational paradigm, an inexact circuit offers a promising approach to significantly reduce both dynamic and static power dissipation for error-tolerant applications. In this paper, an inexact floating-point adder is proposed by approximately designing an exponent sub-tractor and mantissa adder. Related operations such as normaliza-tion and rounding are also dealt with in terms of inexact computing. An upper bound error analysis for the average case is presented to guide the inexact design; it shows that the inexact floating-point adder design is dependent on the application data range. High dynamic range images are then processed using the proposed inexact floating-point adders to show the validity of the inexact design; comparison results show that the proposed inexact floating-point adders can improve the power consumption and power-delay product by 29.98% and 39.60%, respectively.