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Psychiatric and neurodegenerative illnesses are characterized by cognitive impairments, in particular deficits in working memory, decision-making, and executive functions including cognitive flexibility. However, the neuropharmacology of these cognitive functions is poorly understood. The serotonin (5-HT) 2A receptor might be a promising candidate for the modulation of cognitive processes. However, pharmacological studies investigating the role of this receptor system in humans are rare. Recent evidence demonstrates that the effects of Lysergic acid diethylamide (LSD) are mediated via agonistic action at the 5-HT2A receptor. Yet, the effects of LSD on specific cognitive domains using standardized neuropsychological test have not been studied.
We examined the acute effects of LSD (100 µg) alone and in combination with the 5-HT2A antagonist ketanserin (40 mg) on cognition, employing a double-blind, randomized, placebo-controlled, within-subject design in 25 healthy participants. Executive functions, cognitive flexibility, spatial working memory, and risk-based decision-making were examined by the Intra/Extra-Dimensional shift task (IED), Spatial Working Memory task (SWM), and Cambridge Gambling Task (CGT) of the Cambridge Neuropsychological Test Automated Battery.
Compared to placebo, LSD significantly impaired executive functions, cognitive flexibility, and working memory on the IED and SWM, but did not influence the quality of decision-making and risk taking on the CGT. Pretreatment with the 5-HT2A antagonist ketanserin normalized all LSD-induced cognitive deficits.
The present findings highlight the role of the 5-HT2A receptor system in executive functions and working memory and suggest that specific 5-HT2A antagonists may be relevant for improving cognitive dysfunctions in psychiatric disorders.
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.
To assess the effect of topical betahistine on Eustachian tube function in subjectively abnormal subjects in a hyperbaric chamber.
Active and passive Eustachian tube function was examined using tympanometry in a pressure chamber.
Active Eustachian tube function was tested against the negative middle ear pressure induced by increasing the chamber pressure to +3 kPa. One voluntary swallow decreased middle-ear pressure by a mean of 1.36 kPa. Passive Eustachian tube function was tested by measuring spontaneous Eustachian tube openings as the chamber pressure dropped from +10 kPa to ambient. Four distinct patterns of Eustachian tube behaviour were seen, three of which indicated Eustachian tube dysfunction. Betahistine had no positive effect on Eustachian tube opening, although previous animal studies had suggested a beneficial effect.
Topical betahistine had no effect on Eustachian tube function. Combining a hyperbaric chamber with tympanometry proved ideal for evaluating Eustachian tube function.
We present possible conceptual designs of a laser system for driving table-top free-electron lasers based on terahertz acceleration. After discussing the achievable performances of laser amplifiers with Yb:YAG at cryogenic and room temperature and Yb:YLF at cryogenic temperature, we present amplification modules with available results and concepts of amplifier chains based on these laser media. Their performances are discussed in light of the specifications for the tasks within the table-top light source. Technical and engineering challenges, such as cooling, control, synchronization and diagnostics, are outlined. Three concepts for the laser layout feeding the accelerator are eventually derived and presented.
Objectives: Fatigue is a common and persisting symptom after childhood brain injury. This study examined whether child characteristics and symptomatology preinjury or 6 months postinjury (pain, sleep, and mood, inattention) predicted fatigue at 12months postinjury. Methods: Parents of 79 children (0–18 years) rated fatigue at 12 months after injury on a multidimensional scale (general, sleep/rest, and cognitive). Demographic and clinical data were collected at injury. Parents rated child sleep, pain, physical/motor function, mood, and inattention at injury (preinjury description), and 6 months postinjury. Children were divided into two traumatic brain injury severity groups: mild TBI (n=57) and moderate/severe TBI (n=27). Hierarchical regression models were used to examine (i) preinjury factors and (ii) symptoms 6 months postinjury predictive of fatigue (general, sleep/rest, and cognitive) at 12 months postinjury. Results: Sleep/rest fatigue was predicted by preinjury fatigue (7% of variance) and psychological symptoms preinjury (10% of variance). General fatigue was predicted by physical/motor symptoms (27%), sleep (10%) and mood symptoms (9%) 6 months postinjury. Sleep/rest fatigue was predicted by physical/motor symptoms (10%), sleep symptoms (13%) and mood symptoms (9%) 6 months postinjury. Cognitive fatigue was predicted by physical/motor symptoms (17%) 6 months postinjury. Conclusions: Preinjury fatigue and psychological functioning identified those at greatest risk of fatigue 12 months post-TBI. Predictors of specific fatigue domains at 12 months differed across each of the domains, although consistently included physical/motor function as well as sleep and mood symptoms postinjury. (JINS, 2018, 24, 224–236)
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.
The astrometric capability of the Hubble Space Telescope Planetary Camera (WF/PC1) is investigated, motivated by a study of the internal velocity distribution of globular clusters. The astrometric accuracy of the HST PC will be determined ultimately by 1) the accuracy to which the aberrated images can be ‘centered’, and 2) the accuracy to which the distortions across the PC field can be modeled. A series of overlapping exposures of two clusters, NGC 6752 and M15, are utilized to examine these issues.
We have made use of maximum-likelihood image reconstruction to address the first issue, with good success. Reconstruction improves both the detectability and precision of the image centers. A preliminary exploration of the second issue, that of modeling the distortion across the PC field, is also presented, using positions derived from the multiple overlapping exposures.
We report on a target system supporting automated positioning of nano-targets with a precision resolution of
in three dimensions. It relies on a confocal distance sensor and a microscope. The system has been commissioned to position nanometer targets with 1 Hz repetition rate. Integrating our prototype into the table-top ATLAS 300 TW-laser system at the Laboratory for Extreme Photonics in Garching, we demonstrate the operation of a 0.5 Hz laser-driven proton source with a shot-to-shot variation of the maximum energy about 27% for a level of confidence of 0.95. The reason of laser shooting experiments operated at 0.5 Hz rather than 1 Hz is because the synchronization between the nano-foil target positioning system and the laser trigger needs to improve.
Commission 26 has changed its name. The new denomination, warmly promoted by Dommanget, represents more adequately the actual field of the Commission Itself and appears as a good start for extending its interest beyond the traditional aspects (morphology and statistics) and plunging into problems connected with the origin, evolution, mass spectrum and dynamics of small star associations.
An efficient and robust method to measure vitamin D (25-hydroxy vitamin D3 (25(OH)D3) and 25-hydroxy vitamin D2 in dried blood spots (DBS) has been developed and applied in the pan-European multi-centre, internet-based, personalised nutrition intervention study Food4Me. The method includes calibration with blood containing endogenous 25(OH)D3, spotted as DBS and corrected for haematocrit content. The methodology was validated following international standards. The performance characteristics did not reach those of the current gold standard liquid chromatography-MS/MS in plasma for all parameters, but were found to be very suitable for status-level determination under field conditions. DBS sample quality was very high, and 3778 measurements of 25(OH)D3 were obtained from 1465 participants. The study centre and the season within the study centre were very good predictors of 25(OH)D3 levels (P<0·001 for each case). Seasonal effects were modelled by fitting a sine function with a minimum 25(OH)D3 level on 20 January and a maximum on 21 July. The seasonal amplitude varied from centre to centre. The largest difference between winter and summer levels was found in Germany and the smallest in Poland. The model was cross-validated to determine the consistency of the predictions and the performance of the DBS method. The Pearson’s correlation between the measured values and the predicted values was r 0·65, and the sd of their differences was 21·2 nmol/l. This includes the analytical variation and the biological variation within subjects. Overall, DBS obtained by unsupervised sampling of the participants at home was a viable methodology for obtaining vitamin D status information in a large nutritional study.
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.
In this paper we present a first supercloseness analysis for higher-order Galerkin FEM applied to a singularly perturbed convection-diffusion problem. Using a solution decomposition and a special representation of our finite element space, we are able to prove a supercloseness property of p + 1/4 in the energy norm where the polynomial order p ≥ 3 is odd.
The concept of THz detection based on excitation of plasma waves in two-dimensional electron gas in Si FETs is one of the most attractive ones, as it makes possible the development of the large-scale integrated devices based on a conventional microelectronic technology including on-chip antennas and readout devices integration. In this work we report on investigations of Terahertz detectors based on low-cost silicon technology field effect transistors. We show that detectors, consisting of a coupling antenna and a n-MOS field effect transistor as rectifying element, are efficient for THz detection and imaging. We demonstrate that in the atmospheric window around 300 GHz, these detectors can achieve a record noise equivalent power below 10 pW/Hz0.5 and a responsivity above 90 kV/W once integrated with on-chip amplifier. We show also that they can be used in a very wide frequency range: from ∼0.2 THz up to 1.1 THz. THz detection by Si FETs pave the way towards high sensitivity silicon technology based focal plane arrays for THz imaging.
Substrates with extremely low roughness to allow the growth of good-quality silicon material but that nevertheless present high light trapping properties are presented. In a first application, silver reflectors are used in single and tandem-junction amorphous silicon (a-Si:H) solar cells. High initial (stable) efficiencies of 10.4 % (8.1 %) for single-junction a-Si:H cells on glass and 11.1 % (9.2 %) for tandem-junction a-Si:H/a-Si:H cells on plastic are obtained. A second application better suited to multi-junction solar cells based on microcrystalline silicon (μc-Si:H) solar cells is presented: the substrate consists of rough zinc oxide (ZnO) grown on a flat silver reflector which is covered with a-Si:H; polishing of this structure yields an a-Si:H/ZnO interface that provides high light scattering even though the cell is deposited on a flat interface. We present results of ∼ 4-μm-thick μc-Si:H solar cells prepared on such substrates with high open-circuit voltages of 520 mV. A large relative efficiency gain of 20% is observed compared to a co-deposited cell grown directly on an optimized textured substrate.
Silver can be used as the back contact and reflector in thin film silicon solar cells. When deposited on textured substrates, silver films often exhibit reduced reflectance due to absorption losses by the excitation of surface plasmon resonances. We show that thermal annealing of the silver back reflector increases its reflectance drastically. The process is performed at low temperature (150°C) to allow the use of plastic sheets such as polyethylene naphthalate and increases the efficiency of single junction amorphous solar cells dramatically. We present the best result obtained on a flexible substrate: a cell with 9.9% initial efficiency and 15.82 mA/cm2 in short circuit current is realized in n-i-p configuration.