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First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Contemporary ice stream flow is directly linked to conditions at the ice/bed interface, yet this environment is logistically difficult to access. Instead, we investigate subglacial processes important for ice stream flow by studying tills on the deglaciated Antarctic continental shelf. We test currently-accepted hypotheses surrounding subglacial processes and till properties with a Ross Sea dataset. Till shear strengths indicate a continuum of simultaneous processes acting at the bed, rather than discrete ‘deformation’ and ‘lodgement’ end-members. We identify a threshold water content representing saturated pore spaces, leading to basal sliding and meltwater channelization. Based on observations of till properties relative to glacial landforms, we challenge the assumption that low shear strength is linked to intense deformation. Spatial variability in landform morphology reflects variability in deforming processes at the sub-ice stream scale and suggests a maximum deforming bed thickness of 2 m at the grounding line. Regional till properties generally correlate with seafloor geology and deglacial history; the western Ross Sea is characterized by higher and more variable shear strengths and water contents, while lower-shear strength till was preserved in the Eastern Basin. These observations inform till interpretation and provide context for deforming beds beneath the modern ice sheet and on glaciated continental shelves.
As treaties decline, customary international law can be an important mechanism of international cooperation over the medium term. There are increasingly fewer treaties ratified by the United States, with a record-low number of five in 2009–2012, and fewer multilateral treaties adopted worldwide. Yet, the demand for global rules and standards has not abated. Thus, for many international questions where treaties are not available as a source of new rules, customary international law may serve as an interchangeable instrument of national policy.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Nature and origin of the high-velocity clouds (HVCs) remain enigmatic after thirty years (Wakker & van Woerden 1997, ARA&A, 35, 217), owing to lack of distance information. Hypotheses range from supernova shells at 100 pc to intergalactic clouds at 1 Mpc. On statistical grounds, Blitz et al. (1996, BAAS, 28, 1349) claim that the HVCs are “remnants of Local Group formation, best explained as members of the Local Group of galaxies”. Reliable distances must come from the presence or absence of absorption at the HVC's velocity in spectra of stars at different distances. For Complex A, MgII absorption is seen in HST spectra of the Seyfert galaxy Mrk 106, but not in the star PG0859+593 at 4 kpc (Wakker et al. 1996, ApJ, 473, 834). La Palma spectra of the RR Lyr star AD UMa at 11 kpc distance show CaII absorption by Complex A at both K and H, which is lacking at 4 kpc. These absorptions are not confused with stellar metal lines. Our distance bracket 4 < d < 11 kpc places Complex A in the Galactic Halo, at 2.5 < z < 7.5 kpc above the plane; a distance similar to Local Group galaxies is excluded. The HI mass implied lies between 0.15 and 1.2 times 106M⊙. Our result precludes local origins for this HVC. It allows an origin in a Galactic Fountain, or in interaction of infalling intergalactic material (from the Magellanic System or the Local Group) with the Galactic Halo.
Several studies have shown that the combined community-based Meeting Centres Support Programme (MCSP) for people with mild to moderate dementia and their carers were more effective in reducing behavior and mood problems of people with dementia than traditional nursing home-based (NH) day care. We therefore investigated in this study whether community-based (CO) psychogeriatric day care for people with mild to severe dementia combined with carer support (in accordance with the MCSP), is more effective than regular NH day care.
A pre-test–post-test control group design was used to compare the effect of CO and NH day care on care needs, behavior and mood problems, and quality of life of people with dementia. 138 dyads of people with mild to severe dementia and family carers participated in the study: 70 from (new and longer existing) CO day cares (experimental group), and 68 from NH day cares (control group). ANCOVAs were performed at post-tests, including baseline data as covariates.
After six months, no overall differences on outcome measures were found between CO and NH day cares. However, participants of recently started CO day cares showed fewer neuropsychiatric symptoms, whereas carers in the longer existing CO day cares reported fewer care needs compared to the control group (large effects). Persons with dementia cohabiting with their carer benefitted most from CO day care.
This study shows that combined CO day care has promising added value compared to NH day care, especially for participants with dementia cohabiting with their carer.
Tic disorders are moderately heritable common psychiatric disorders that can be highly troubling, both in childhood and in adulthood. In this study, we report results obtained in the first epigenome-wide association study (EWAS) of tic disorders. The subjects are participants in surveys at the Netherlands Twin Register (NTR) and the NTR biobank project. Tic disorders were measured with a self-report version of the Yale Global Tic Severity Scale Abbreviated version (YGTSS-ABBR), included in the 8th wave NTR data collection (2008). DNA methylation data consisted of 411,169 autosomal methylation sites assessed by the Illumina Infinium HumanMethylation450 BeadChip Kit (HM450k array). Phenotype and DNA methylation data were available in 1,678 subjects (mean age = 41.5). No probes reached genome-wide significance (p < 1.2 × 10−7). The strongest associated probe was cg15583738, located in an intergenic region on chromosome 8 (p = 1.98 × 10−6). Several of the top ranking probes (p < 1 × 10−4) were in or nearby genes previously associated with neurological disorders (e.g., GABBRI, BLM, and ADAM10), warranting their further investigation in relation to tic disorders. The top significantly enriched gene ontology (GO) terms among higher ranking methylation sites included anatomical structure morphogenesis (GO:0009653, p = 4.6 × 10−15) developmental process (GO:0032502, p = 2.96 × 10−12), and cellular developmental process (GO:0048869, p = 1.96 × 10−12). Overall, these results provide a first insight into the epigenetic mechanisms of tic disorders. This first study assesses the role of DNA methylation in tic disorders, and it lays the foundations for future work aiming to unravel the biological mechanisms underlying the architecture of this disorder.
Fluctuations in Zn metabolism throughout gestation and lactation might affect Zn requirements. However, scientific data on Zn requirements for breeding sows are limited. The objective of the present study was to assess the Zn status of primiparous and multiparous sows using different Zn status biomarkers, to identify periods of critical Zn status throughout the reproductive cycle at different parities. Blood samples were taken after overnight fasting before feeding in the morning from five primiparous and ten multiparous sows at fixed time intervals during gestation (days − 5, 0 (insemination), 21, 42, 63 and 84), around parturition (days 108, 112, 115 (parturition) and 118) and during lactation (days 122, 129 and 143 (weaning)). At parturition, blood samples were collected from two randomly selected piglets per sow before colostrum intake. Plasma was analysed for Zn and Cu contents, whereas serum was analysed for alkaline phosphatase, metallothionein and albumin concentrations. Independently of parity, all biomarkers fluctuated differently during gestation and lactation (P< 0·050). This reflects their different roles in Zn metabolism, and suggests that the choice of a Zn status biomarker necessitates careful consideration. Low average plasma Zn concentration at the end of gestation and throughout lactation seem to be replenished towards weaning.
We present the results of an approximately 6 100 deg2 104–196 MHz radio sky survey performed with the Murchison Widefield Array during instrument commissioning between 2012 September and 2012 December: the MWACS. The data were taken as meridian drift scans with two different 32-antenna sub-arrays that were available during the commissioning period. The survey covers approximately 20.5 h < RA < 8.5 h, − 58° < Dec < −14°over three frequency bands centred on 119, 150 and 180 MHz, with image resolutions of 6–3 arcmin. The catalogue has 3 arcmin angular resolution and a typical noise level of 40 mJy beam− 1, with reduced sensitivity near the field boundaries and bright sources. We describe the data reduction strategy, based upon mosaicked snapshots, flux density calibration, and source-finding method. We present a catalogue of flux density and spectral index measurements for 14 110 sources, extracted from the mosaic, 1 247 of which are sub-components of complexes of sources.
Antipsychotic drugs (APD) are widely prescribed for people with dementia residing in long term care facilities (LTCFs). Concern has been expressed that such prescribing is largely inappropriate. The objective of this study is to examine if differences in facility-level prevalence of APD use in a sample of LTCFs for patients with dementia can be explained by patient and facility-related characteristics.
A point prevalence study was conducted using data from the VU University Resident Assessment Instrument (VURAI) database from nursing homes and residential care facilities in the Netherlands. Patients were selected who had a diagnosis of dementia. LTCF and patient characteristics were extracted from the VURAI; facility-level resident satisfaction surveys were provided by the National Institute for Public Health.
In total, 20 LTCFs providing care for 1,090 patients with dementia were investigated. Overall, 31% of patients used an APD. In facilities with a high prevalence of APD use behavioral symptoms were present in 62% of their patients. In facilities with medium APD use behavioral problems remained frequent (57%), and in facilities with low prevalence of APD use 54% of the patients had behavioral symptoms. Facilities with a high prevalence of APD use were often large, situated in urban communities, and scored below average on staffing, personal care, and recreational activities.
There was considerable variation between the participating LTCFs in the prevalence of APD use. Variability was related to LTCF characteristics and patient satisfaction. This indicates potential inappropriate prescribing because of differences in institutional prescribing culture.
Galactic short period double white dwarfs (DWD) are guaranteed gravitational wave (GW) sources for the next generation of space-based interferometers sensitive to low-frequency GWs (10−4− 1 Hz). Here we investigate the possibility of constraining the white dwarf (WD) properties through measurements of apsidal precession in eccentric binaries. We analyze the general relativistic (GR), tidal, and rotational contributions to apsidal precession by using detailed He WD models. We find that apsidal precession can lead to a detectable shift in the emitted GW signal, the effect being stronger (weaker) for binaries hosting hot (cool) WDs. We find that in hot (cool) DWDs tides dominate the precession at orbital frequencies above ~0.01 mHz (~1 mHz). Analyzing the apsidal precession of these sources only accounting for GR would potentially lead to an extreme overestimate of the component masses. Finally, we derive a relation that ties the radius and apsidal precession constant of cool WD components to their masses, therefore allowing tides to be used as an additional mass measurement tool.
In future technology nodes, 22nm and below, carbon nanotubes (CNTs) may provide a viable alternative to Cu as an interconnect material. CNTs exhibit a current carrying capacity (up to 109 A/cm2), whilst also providing a significantly higher thermal conductivity (SWCNT ~ 5000 WmK) over Copper (106 A/cm2 and ~400WmK). However, exploiting such properties of CNTs in small vias is a challenging endeavor. In reality, to outperform Cu in terms of a reduction in via resistance alone, densities in the order of 1013 CNTs/cm2 are required. At present, conventional thermal CVD of carbon nanotubes is carried out at temperatures far in excess of CMOS temperature limits (400 C). Furthermore, high density CNT bundles are most commonly grown on insulating supports such as Al2O3 and SiO2 as they can effectively stabilize metallic nanoparticles at elevated temperatures but this limits their application in electronic devices. To circumvent these obstacles we employ a remote microwave plasma to grow high density CNTs at a temperature of 400 C on conductive underlayers such as TiN. We identify some critical factors important for high-quality CNTs at low temperatures such as control over the catalyst to underlayer interaction and plasma growth environment while presenting a fully CMOS compatible carbon nanotube synthesis approach
Neuronal research requires to efficiently perform long-time experiments on large-scale neuronal networks in a minimally invasive way. Such experiments imply stimulation and measurements of electrical activity on a large number of neurons. This could be achieved by on-chip integration of actuators, sensors and readout electronics with dimensions comparable to the sizes of neurons. Integration of biosensors at this scale creates new challenges: the processing of the sensors must be compatible with state-of-the art CMOS technology, the system must be biocompatible, and the down-scaled technology imposes restrictions on the applicable stimulation voltages and increases the electrical noise.
Recently it has been demonstrated that biological phenomena can be exploited in order to achieve the best coupling between cells and sub-micron scale electronics. Engulfment of sub-micron nail structures by the cell membrane minimizes the distance between the sensor and the cell , .
This paper presents two methods to produce nails with sizes from sub-micrometer to micrometer scales, on top of a CMOS chip. Prototype chips have been fabricated, and cells have been cultured to examine the in-vitro bio-compatibility of the chip.
Oriented gases of biopolymers in simple, single crystal hosts might be used to measure anisotropic molecular properties of analytes that could not otherwise be crystallized. Here we show two types of crystals as examples of the single crystal matrix isolation of biopolymers: green fluorescent protein in α-lactose monohydrate as a model system for studying the kinetic stabilization of biopharmaceuticals, and adenosine phosphates in potassium dihydrogen phosphate, a first step in the matrix isolation of oligonucleotides. In each case, the hosts undergo compositional zoning – both intersectoral and intrasectoral – during growth from solution. Intrasectoral zoning is evident by the selective luminescence of adjacent vicinal slopes of growth active hillocks. Nucleotides furthermore distinguish between symmetry related growth sectors enantioselectively.