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Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Background: Continuous video-EEG (cvEEG) monitoring is the standard of care for diagnosis and management of neonatal seizures. However, it is labour-intensive. We aimed to establish consistency in monitoring of newborns utilising NICU nurses. Methods: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues. Guidelines, checklists and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. We compared 100 infants with moderate to severe HIE before and after the training program. Results: 192 cvEEGs were performed. Of the 100 infants compared; time to initiate brain monitoring decreased by average of 31.5 hours, in electrographic seizure detection increased(20% compared to 34% a), seizure clinical misdiagnosis decreased (65% compared to 36% ), and Anti-Seizure burden decreased. Conclusions: Training experienced NICU nurses to set-up, start and monitor cvEEG can decrease the time to initiate cvEEG which may lead to better seizure diagnosis and management.
Background: Despite advances in neonatal care, neonates with moderate to severe HIE are at high risk of mortality and morbidity. we report the impact of a dedicated NNCC team on short term mortality and morbidities. Methods: A retrospective cohort study on neonates with moderate to serve HIE between July 1st 2008 and December 31st 2017. primary outcome : a composite of death and/or brain injury on MRI. Secondary outcomes: rate of cooling, length of hospital stay, anti-seizure medication burden, and use of inotropes. A regression analysis was done adjusting for gestational age, birth weight, gender, out-born status, Apgar score at 10 minutes, cord blood pH, and HIE clinical staging Results: 216 neonates were included, 109 before NNCC implementation, and 107 thereafter. NNCC program resulted in reduction in the primary outcome (AOR: 0.28, CI: 0.14-0.54, p<0.001) and brain injury (AOR: 0.28, CI: 0.14-0.55, p<0.001). It decreased average length of stay/infants by 5 days (p=0.03), improved cooling rate (73% compared to 93% , p <0.001), reduced: seizure misdiagnosis (71% compared to 23%, P <0.001), anti-seizure medication burden (P = 0.001), and inotrope use (34% compared to 53%, p=0.004) Conclusions: NNCC program decreased mortality and brain injury , shortened the length of hospital stay and improved care of neonates with significant HIE.
Five size traits (body weight, heart girth, hip height, body depth and rump width) and three yield traits (milk, fat and protein) of 7192 heifers were analysed on a monthly and 305-day lactation basis. The additive genetic variation was moderate to high and changed over time. Correlations between observations measured in different months were all >0.89. Covariance methodology was used to reduce the number of parameters to estimate the variance components. Correlations between size and yield traits ranged from -0.14 to 0.26; this study did not indicate that these correlations were time-dependent.
More information about the pattern of behavioural and psychological symptoms of dementia (BPSD) in the course of dementia is needed to inform patients and clinicians and to design future interventions.
To determine the persistence and incidence of BPSD and their relation to cognitive function, in individuals with dementia or in cohorts investigated for dementia onset.
A systematic literature review analysed the baseline prevalence, persistence and incidence of 11 symptoms. The review was conducted according to established guidelines with the exception that we could not exclude the possibilities of bias in the studies examined.
The 59 included studies showed considerable heterogeneity in their objectives and methods. The symptoms hyperactivity and apathy showed high persistence and incidence; depression and anxiety low or moderate persistence and moderate incidence; and psychotic symptoms low persistence with moderate or low incidence.
Despite heterogeneity across studies in terms of setting, focus and length of follow-up, there were clinically relevant differences in the longitudinal courses of different BPSD. Apathy was the only symptom with high baseline prevalence, persistence and incidence during the course of dementia.
Psychosocial therapy after deliberate self-harm might be associated with reduced risk of specific causes of death.
In this matched cohort study, we included patients, who after an episode of deliberate self-harm received psychosocial therapy at a Suicide Prevention Clinic in Denmark between 1992 and 2010. We used propensity score matching in a 1:3 ratio to select a comparison group from 59 046 individuals who received standard care. National Danish registers supplied data on specific causes of death over a 20-year follow-up period.
At the end of follow-up, 391 (6.9%) of 5678 patients in the psychosocial therapy group had died, compared with 1736 (10.2%) of 17 034 patients in the matched comparison group. Lower odds ratios of dying by mental or behavioural disorders [0.54, 95% confidence interval (CI) 0.37–0.79], alcohol-related causes (0.63, 95% CI 0.50–0.80) and other diseases and medical conditions (0.61, 95% CI 0.49–0.77) were noted in the psychosocial therapy group. Also, we found a reduced risk of dying by suicide as well as other external causes, however, not by neoplasms and circulatory system diseases. Numbers needed to treat were 212.9 (95% CI 139.5–448.4) for mental or behavioural disorders as a cause of death, 111.1 (95% CI 79.2–210.5) for alcohol-related causes and 96.8 (95% CI 69.1–161.8) for other diseases and medical conditions.
Our findings indicate that psychosocial therapy after deliberate self-harm might reduce long-term risk of death from select medical conditions and external causes. These promising results should be tested in a randomized design.
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.
Blazar OJ 287 is one of the best observed extragalactic objects. It's historical light curve goes back to 1890′s. Based on the historical behaviour Sillanpää et al. (1988) showed that OJ 287 displays large periodic outbursts, with a period of 11.7 years. We have monitored OJ 287 intensively for two years, during the OJ-94 project. This project was created for monitoring OJ 287 during its predicted new outburst in 1994. In the data archive we have over 7000 observations on OJ 287, in the radio, infrared and optical bands. This data archive contains the best ever obtained light curves for any extragalactic object. The optical light curve shows continuous variability down to time scales of tens of minutes. The variability observed in OJ 287 can be broken down to (at least) four different categories:
Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in ‘frequency of internet use’ was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in ‘frequency of use after 11 pm’, ‘using the internet to contact peers’, and ‘using the internet primarily to access social networking sites’ was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between ‘frequency of internet use’ and ‘frequency of use after 11 pm’ with social phobia (SP). ‘Using the internet to contact peers’ was positively associated with alcohol abuse, whereas ‘using the internet to contact peers’ and ‘using the internet primarily to access social networking sites’ were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology.
Generally, there is a need for short questionnaires to estimate diet quality in the Netherlands. We developed a thirty-four-item FFQ – the Dutch Healthy Diet FFQ (DHD-FFQ) – to estimate adherence to the most recent Dutch guidelines for a healthy diet of 2006 using the DHD-index. The objectives of the present study were to evaluate the DHD-index derived from the DHD-FFQ by comparing it with the index based on a reference method and to examine associations with participant characteristics, nutrient intakes and levels of cardiometabolic risk factors. Data of 1235 Dutch men and women, aged between 20 and 70 years, participating in the Nutrition Questionnaires plus study were used. The DHD-index was calculated from the DHD-FFQ and from a reference method consisting of a 180-item FFQ combined with a 24-h urinary Na excretion value. Ranking was studied using Spearman’s correlations, and absolute agreement was studied using a Bland–Altman plot. Nutrient intakes derived from the 180-item FFQ were studied according to quintiles of the DHD-index using DHD-FFQ data. The correlation between the DHD-index derived from the DHD-FFQ and the reference method was 0·56 (95 % CI 0·52, 0·60). The Bland–Altman plot showed a small mean overestimation of the DHD-index derived from the DHD-FFQ compared with the reference method. The DHD-index score was in the favourable direction associated with most macronutrient and micronutrient intakes when adjusted for energy intake. No associations between the DHD-index score and cardiometabolic risk factors were observed. In conclusion, the DHD-index derived from the DHD-FFQ was considered acceptable in ranking but relatively poor in individual assessment of diet quality.
The Dutch Healthy Diet index (DHD-index) was developed using data from two 24 h recalls (24hR) and appeared useful to evaluate diet quality in Dutch adults. As many epidemiologic studies use FFQ, we now estimated the DHD-index score using FFQ data. We compared whether this score showed similar associations with participants' characteristics, micronutrient intakes, and biomarkers of intake and metabolism compared with the DHD-index using 24hR data. Data of 121 Dutch participants of the European Food Consumption Validation study were used. Dietary intake was assessed by two 24hR and a 180-item FFQ. Biomarkers measured were serum total cholesterol and carotenoids, EPA + DHA in plasma phospholipids and 24 h urinary Na. A correlation of 0·48 (95 % CI 0·33, 0·61) was observed between the DHD-index score based on 24hR data and on FFQ data. Classification of participants into the same tertiles of the DHD-index was achieved for 57 %. Women showed higher DHD-index scores. Energy intake was inversely associated with both DHD-index scores. Furthermore, age and intakes of folate, Fe, Mg, K, vitamin B6 and vitamin C were positively associated with both DHD-index scores. DHD-index scores showed acceptable correlations with the four combined biomarkers taking energy intake into account (r24hR 0.55; rFFQ 0.51). In conclusion, the DHD-index score based on FFQ data shows similar associations with participants' characteristics, energy intake, micronutrient intake and biomarkers compared with the score based on 24hR data. Furthermore, ranking of participants was acceptable for both methods. FFQ data may therefore be used to assess diet quality using the DHD-index in Dutch populations.
The breeding scheme of a Swiss sire line was modeled to compare different target traits and information sources for selection against boar taint. The impact of selection against boar taint on production traits was assessed for different economic weights of boar taint compounds. Genetic gain and breeding costs were evaluated using ZPlan+, a software based on selection index theory, gene flow method and economic modeling. Scenario I reflected the currently practiced breeding strategy as a reference scenario without selection against boar taint. Scenario II incorporated selection against the chemical compounds of boar taint, androstenone (AND), skatole (SKA) and indole (IND) with economic weights of −2.74, −1.69 and −0.99 Euro per unit of the log transformed trait, respectively. As information sources, biopsy-based performance testing of live boars (BPT) was compared with genomic selection (GS) and a combination of both. Scenario III included selection against the subjectively assessed human nose score (HNS) of boar taint. Information sources were either station testing of full and half sibs of the selection candidate or GS against HNS of boar taint compounds. In scenario I, annual genetic gain of log-transformed AND (SKA; IND) was 0.06 (0.09; 0.02) Euro, which was because of favorable genetic correlations with lean meat percentage and meat surface. In scenario II, genetic gain increased to 0.28 (0.20; 0.09) Euro per year when conducting BPT. Compared with BPT, genetic gain was smaller with GS. A combination of BPT and GS only marginally increased annual genetic gain, whereas variable costs per selection candidate augmented from 230 Euro (BPT) to 330 Euro (GS) or 380 Euro (both). The potential of GS was found to be higher when selecting against HNS, which has a low heritability. Annual genetic gain from GS was higher than from station testing of 4 full sibs and 76 half sibs with one or two measurements. The most effective strategy to reduce HNS was selecting against chemical compounds by conducting BPT. Because of heritabilities higher than 0.45 for AND, SKA and IND and high genetic correlations to HNS, the (correlated) response in units of the trait could be increased by 62% compared with scenario III with GS and even by 79% compared with scenario III, with station testing of siblings with two measurements. Increasing the economic weights of boar taint compounds amplified negative effects on average daily gain, drip loss and intramuscular fat percentage.
Recent studies have suggested significant variations in radiotherapy schedules used to treat advanced non-small-cell lung cancer (NSCLC), both between different centers in one country as well as between countries. In this study, different treatment methodologies have been explored using management plans proposed by radiation oncologists regarding general questions and theoretical case histories for patients with advanced NSCLC.
Materials and methods
The survey was conducted by sending a questionnaire to 24 radiotherapy centers in Europe. The questionnaire was composed of two sections. The first section concerned reasons for giving radiotherapy, parameters that influence the choice of total dose and fractionation for radiotherapy and kind of equipment used. The second section concerned the management of five theoretical patients (A–E) regarding the selection of the radiotherapy technique and the aim of treatment (radical or palliative). Furthermore, 19 trials comparing different regimens of palliative radiotherapy in patients with NSCLC were reviewed. There were marked differences in the doses of the investigated radiotherapy schemes, the patient characteristics and the assessed outcome measures.
70% of the responders answered that the most important factors for deciding what dose and fractionation scheme to use were: metastases, performance status (PS) of the patient, lung function and size of the primary tumour. The most common reasons for giving the treatment were symptom relief, prolongation of life and, in some cases, possibly cure. More than 95% of the responders stated that they would give radiotherapy in each of these cases. The total doses proposed where 20 Gy in five fractions or 30 Gy in ten fractions in 2 weeks for the cases A and D. If the previous two schemes were converted to a fractionation scheme delivering 2 Gy per fraction, the equivalent doses would be 23 and 33 Gy, respectively. For the cases B, C and E, the proposed fractionation schemes were 2 Gy daily to 60–68 Gy in 6 weeks or 2 Gy daily to 68 Gy in 7 weeks. For the case E, 20% of the responders suggested Stereotactic Body Radiotherapy (SBRT) giving 21 Gy three times a week with a day apart to 63 Gy. The total dose and number of fractions of radiotherapy are related to the perceived aims and expectations of treatment. Those aiming at extending life would give significantly higher total doses in a larger number of fractions, whereas those aiming at relieving symptoms would give significantly lower total doses. There is evidence for an increase in survival, in patients who are given higher radiotherapy doses, especially in those patients with better PS.
This survey demonstrates a range of treatment strategies for advanced and inoperable NSCLC within Europe. There are a number of factors that influence the perceived aims of treatment and treatment planning. These factors should be taken into account when evaluating the effectiveness of different irradiation techniques, especially in the determination of radiobiological parameters and dose–response relations. The majority of patients should be treated with short courses of palliative radiotherapy, of one or two fractions. The use of high-dose palliative regimens using many fractions or SBRT should be considered for selected patients with good PS.
The role of interfacial exchange coupling in the magnetic behavior of metal oxide materials has been investigated through the study of Fe3O4/NiO superlattices. We report results on a series of superlattices grown where one bilayer constituent was held to a fixed thickness while varying the other from single unit cell dimensions upward. High crystalline quality was confirmed by XRD, RHEED and neutron diffraction. Magnetization profiles show substantial deviations from bulklike iron oxide results, with an increase in domain rotation energies observed in the superlattices over that of bulk iron oxide (increasing with NiO layer thickness) indicating the strong nature of Fe3O4/NiO interfacial linkage. Neutron scattering at elevated temperatures shows that the NiO remains ordered above the 523 K bulk Néel temperature. This suggests that at least a portion of the NiO within a layer remains ordered well above the Néel temperature, with an increase in effective Néel transition temperature that approaches the Fe3O4 Curie temperature in the limit of very thin NiO layers. Although the exchange coupling dominates these effects, strain also plays an important role.
In 2011, the Fulbright Scholar Program celebrates its 65th anniversary as America's preeminent international educational exchange program. In recognition of its international impact, this is a timely occasion to recall the program's history and note the roles of political scientists who have taught and conducted research around the globe as Fulbright Scholars.
We have investigated the structural and compositional changes that are induced by the segregation of substrate Mg to the surface of 1μm-thick Fe3O4 films on MgO(001). The thin films have been grown with plasma-assisted MBE, and characterization with RHEED (reflection high-energy electron diffraction), x-ray diffraction (XRD), and Superconducting Quantum Interference Device (SQUID) magnetometry show slightly strained, single-crystalline Fe3O4 films. For the surface studies, we have combined Low-Energy Electron Diffraction (LEED) and Scanning Tunneling Microscopy (STM). Initial and final surface characterization employed X-ray Photoelectron Spectroscopy (XPS) and Ion Scattering Spec-troscopy (ISS) respectively. The surfaces of the MBE-grown samples are flat and show a (√2 × √2)R45° reconstruction with respect to the Fe3O4 surface unit cell. We observe the onset of Mg segregation to the surface at around 700 K, with long, narrow extensions of terraces being observed growing along the  and  directions. Upon prolonged heating at 800 K, massive Mg segregation to the surface is observed. Heating in an oxygen atmosphere induces a 1×4 surface reconstruction, and results in extremely long (≈ 1000 Å), wide terraces.
Image sensors in TFA (Thin Film on ASIC) technology have been successfully fabricated and tested. This paper provides a survey of TFA research results so far and outlines future perspectives. The properties of different a-Si:H b/w and color thin film detectors are evaluated, including spectral sensitivity, dark current, temperature influence and transient behavior. Furthermore several TFA prototypes and emerging concepts are presented, ranging from a simple one-transistor cell design to a locally autoadaptive sensor.