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To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.
Epoch of Reionisation (EoR) data analysis requires unprecedented levels of accuracy in radio interferometer pipelines. We have developed an imaging power spectrum analysis to meet these requirements and generate robust 21 cm EoR measurements. In this work, we build a signal path framework to mathematically describe each step in the analysis, from data reduction in the Fast Holographic Deconvolution (FHD) package to power spectrum generation in the εppsilon package. In particular, we focus on the distinguishing characteristics of FHD/εppsilon: highly accurate spectral calibration, extensive data verification products, and end-to-end error propagation. We present our key data analysis products in detail to facilitate understanding of the prominent systematics in image-based power spectrum analyses. As a verification to our analysis, we also highlight a full-pipeline analysis simulation to demonstrate signal preservation and lack of signal loss. This careful treatment ensures that the FHD/εppsilon power spectrum pipeline can reduce radio interferometric data to produce credible 21 cm EoR measurements.
‘The oceans not only contain most of the planet, but also most of the wide variety of living things’ (Pope Francis, 2015). With this statement, Pope Francis summarised a central point about life on Earth: we cannot understand and protect Earth’s biodiversity without considering the ocean. Covering over 70 per cent of the Earth’s surface, the ocean represents an estimated 99 per cent of its habitable living space (Costanza, 1999). The ocean harbours a remarkably rich diversity of species, with almost twice as many major groups, or phyla, of animals living in the ocean as on land. (Of the 34 known phyla of animals, 33 are found in the ocean and only 12 are found on land.) A single type of marine habitat, the coral reef, holds over 50 per cent more phyla than all terrestrial and freshwater habitats combined, despite having a surface area more than 460 times smaller (Birkeland, 2015).
The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.
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.
Thin film metallization is used on integrated circuit chips and ceramic and/or organic substrates for a number of different purposes, On chips the metallization forms Ohmic and Schottky Barrier Diode contact to the semiconductor and the electrical properties of these contacts are strongly influenced by the metals used. Interaction of the metal and semiconductor during processing can result in major variations in the electrical properties of the contacts, Chip metallization is also employed to provide electrical interconnection between devices on a chip. The interconnections can all be made in a single layer, or for more complex chips, a number of layers might be employed using dielectric layers to separate metal layers and via holes through the dielectric for layer-to-layer interconnection. Chip metallization is also used to form the interconnections between the chips and the substrate carrier.
A 15-month-old child underwent percutaneous expansion of a Melody transcatheter pulmonary valve in the mitral position to accommodate growth after initial surgical implantation during infancy, but transiently decompensated after valvuloplasty owing to stent malformation. The Melody valve in the mitral position of small patients can be further expanded by percutaneous dilation, but there are a number of potential complications and technical improvements to consider.
Scrutiny of Herodotus’ ethnographic accounts of northern Syria and the region he calls ‘Palestinian Syria’ reveals oddities and inconsistencies. Here it is argued that such problems may be resolved if a fundamental fact is recognized: the enormous early literary prestige of the Phoenicians has obscured the historical roles of these other peoples in the Histories. The character and extent of this process, specifically as it bears on Syria-Palestine during Iron Age II, is analysed here. It is hoped that a new appreciation of the Syrians as an ethnicity may be gained as a result. It is suggested as well that for important historical problems researchers should ascertain whether Herodotus is not actually talking about Syrians when he discusses Phoenicians.
Examination gloves have been previously noted as a possible barrier to hand hygiene. We performed a prospective quantitative and qualitative study to investigate. Glove usage was found to be a potential barrier to hand hygiene; this was driven by desire for personal safety and potentially learned during professional training.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Nitrogen (N) is a difficult nutrient to manage in organic farming systems, and yield reductions related to N deficiency have been reported in organic systems. Legume-based cover crops offer opportunities for biologically fixed N; however, improved quantification of N contribution is needed for cost-effective N management. A 2-yr experiment was conducted near Corvallis, OR, USA, in 2007 and 2008 to (1) evaluate biomass production and N accumulation from selected cover crop treatments, (2) compare the effects of fall-planted cover crops on broccoli [(Brassica oleraceae L. (Italica group)] yield, (3) estimate the quantity of feather meal-N replaced by cover crops. Cover crop treatments included common vetch (Vicia sativa L.), phacelia (Phacelia tanacetifolia Benth), oats (Avena sativa L.) and the mixtures phacelia plus vetch, oats plus vetch and a no-cover crop (fallow) treatment as the control. Using feather meal as an N source, four rates of N fertilizer (0, 100, 200 and 300 kg N ha−1) were randomized within each cover crop treatment in a randomized, split-plot design. Cover crop biomass and N accumulation differed between the 2 yr of the study. In 2007, total biomass accumulation ranged from 5000 to 10,000 kg ha−1, whereas in 2008, cover crop accumulation was 1500 to 5000 kg ha−1. Biomass of both phacelia and vetch (in mixtures or as sole crops) was reduced by 80% from 2007 to 2008, whereas oat biomass and weed biomass in the fallow plots was reduced by only 40% between the 2 yr. The accumulation of N was also reduced in 2008, with vetch (either as a sole crop or in mixtures) contributing less than a third of total N produced in 2007. In 2007, vetch and vetch-based cover crop mixtures increased broccoli yield compared with the fallow, providing 100–135 kg fertilizer equivalent N ha−1. But due to decreased cover crop biomass and N accumulation in 2008, vetch and vetch-based mixtures failed to increase broccoli yield, providing <20 kg N ha−1 fertilizer equivalence. In 2007, oats grown as a sole cover crop reduced broccoli yield when no supplemental N was applied. In 2008, both phacelia and oats reduced broccoli yield at all N levels, with estimated N fertilizer equivalence values of −80 to −95 kg N ha−1. Although legume and legume mixtures increased broccoli yield in only 1 yr of the experiment, addition of vetch to the mixtures reduced yield loss in both years compared with oats and phacelia grown as sole crops.
Catherine Zuckert's Machiavelli's Politics offers an unprecedented interpretation of all of Machiavelli's major works. Her interpretation places Machiavelli in his historical context as he understood it and shows Machiavelli seeking a populist alternative in politics. Because her approach and her conclusion have been championed by scholars explicitly opposed to Strauss's interpretation of Machiavelli, she intervenes in the scholarly debates on Machiavelli by drawing seemingly opposed approaches closer together. Strauss acknowledges the importance of Machiavelli's historical situation and understands him as a type of democrat. Nevertheless, in highlighting the functioning of Machiavelli's republic, Zuckert directly challenges Strauss, who, she argues, focuses too narrowly on Machiavelli's war on Christianity to explicate fully Machiavelli's politics. Religion and politics, though, are inextricably linked in Machiavelli's thought, and his treatment of Christianity's ascendency offers insight into his new republicanism. Consideration of Montesquieu's commentary on Machiavelli underscores some of the excesses of the Florentine's political solutions.
Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social–emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional–translational research to inform interventions for at-risk families.
One indication for intervention in coarctation of the aorta is a peak-to-peak gradient >20 mmHg. Gradients may be masked in patients under general anaesthesia and may be higher during exercise. Isoproterenol was given during cardiac catheterisation to simulate a more active physiologic state.
We aimed to describe the haemodynamic effects of isoproterenol in patients with coarctation and the impact of intervention on the elicited gradients.
A retrospective study was performed on two-ventricle patients who underwent cardiac catheterisation for coarctation with isoproterenol testing.
25 patients received isoproterenol before and after intervention. With isoproterenol, the mean diastolic (p=0.0015) and mean arterial (p=0.0065) blood pressures proximal to the coarctation decreased significantly. The mean systolic, diastolic, and mean arterial blood pressures distal to the coarctation decreased significantly (p<0.0001). In patients with a baseline gradient ⩽20 mmHg (n=17) at catheterisation, the median gradient increased from 10 (0–20) to 30 (15–50) mmHg (p<0.0001) with isoproterenol. Of these, 15 patients developed a gradient >20 mmHg. Post intervention, the median gradient decreased to 2 (0–29) mmHg, versus baseline, p=0.005, and with isoproterenol it decreased to 8 (0–27) mmHg, versus pre-intervention isoproterenol, p<0.0001. There were significant improvements in the gradients by Doppler (<0.0001) and by blood pressure cuff (p=0.0313). The gradients on isoproterenol best correlated with gradients by blood pressure cuff in the awake state (R2=0.76, p<0.0001).
Isoproterenol can be a useful tool to assess the significance of a coarctation and the effectiveness of an intervention. Percutaneous interventions can effectively reduce the gradients elicited by isoproterenol.
Alcohol use disorder (AUD) has been a major cause of family, social, and personal strife for centuries, with current prevalence estimates of 14% for 12-month and 29% lifetime AUD. Neuropsychological testing of selective cognitive, sensory, and motor functions complemented with in vivo brain imaging has enabled tracking the consequences of AUD, which follows a dynamic course of development, maintenance, and recovery or relapse. Controlled studies of alcoholism reviewed herein provide evidence for disruption of selective functions involving executive, visuospatial, mnemonic, emotional, and attentional processes, response inhibition, prosody, and postural stability and brain systems supporting these functions. On a hopeful front, longitudinal study provides convincing evidence for improvement in brain structure and function following sustained sobriety. These discoveries have a strong legacy in the International Neuropsychological Society (INS), starting from its early days when assumptions regarding which brain regions were disrupted relied solely on patterns of functional sparing and impairment deduced from testing. This review is based on the symposium presentation delivered at the 2017 annual North American meeting of the INS in celebration of the 50th anniversary since its institution in 1967. In the spirit of the meeting’s theme, “Binding the Past and Present,” the lecture and this review recognized the past by focusing on early, rigorous neuropsychological studies of alcoholism and their influence on research currently conducted using imaging methods enabling hypothesis testing of brain substrates of observed functional deficits. (JINS, 2017, 23, 843–859)
Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case–control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry.
We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD.
This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids.
Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.
Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other.
We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes.
Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility.
Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.