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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Fast and efficient identification is critical for reducing the likelihood of weed establishment and for appropriately managing established weeds. Traditional identification tools require either knowledge of technical morphological terminology or time-consuming image matching by the user. In recent years, deep learning computer vision models have become mature enough to enable automatic identification. The major remaining bottlenecks are the availability of a sufficient number of high-quality, reliably identified training images and the user-friendly, mobile operationalization of the technology. Here, we present the first weed identification and reporting app and website for all of Australia. It includes an image classification model covering more than 400 species of weeds and some Australian native relatives, with a focus on emerging biosecurity threats and spreading weeds that can still be eradicated or contained. It links the user to additional information provided by state and territory governments, flags species that are locally reportable or notifiable, and allows the creation of observation records in a central database. State and local weed officers can create notification profiles to be alerted of relevant weed observations in their area. We discuss the background of the WeedScan project, the approach taken in design and software development, the photo library used for training the WeedScan image classifier, the model itself and its accuracy, and technical challenges and how these were overcome.
Small angle X-ray scattering curves have been obtained for a series of Na Wyoming Bentonite clay samples containing 10% clay by weight and NaPO3 in concentrations ranging from 0 to 100 meq/1. From the scattering data, the relative probability of spacings between parallel clay platelets was computed. For the sample containing no NaPO3, the probability distribution showed a relatively broad maximum at an interparticle spacing of about 180Å. As the concentration of NaPO3 increased, the maximum became sharper and occurred for smaller interparticle distances. At NaPO3 concentrations between 25 and 100 meq/1, the position d of the maximum was given approximately by the equation d = 21 + 18.4c-1/2, where d is in angstroms, and c is the NaPOs concentration in eq/1. The similarity of this relation to the dependence of d on the concentration of NaCl (Norrish and Rausell-Colom, 1963; Norrish, 1954) suggests that the interparticle spacing depends primarily on the sodium ion concentration and not on the concentration of the anion. The value of d appears to be independent of whether the gel was prepared by the method of Norrish and Rausell-Colom, in which a dried flake was allowed to come to equilibrium with an electrolyte solution, or whether, as in this investigation, the gel was obtained by centrifuging a dilute suspension. Since the Na ions act to reduce the double-layer repulsion between platelets, while the anions tend to be adsorbed on the platelet edges and thus reduce the edge-to-face linkages (H. van Olphen, 1962), the value of the most probable interparticle distance appears to be determined primarily by the magnitude of the double-layer repulsion, even though other properties of the clay gels, such as the rheological behavior, are governed mainly by edge-to-face attractions.
Control of massive hemorrhage (MH) is a life-saving intervention. The use of tourniquets has been studied in prehospital and battlefield settings but not in aquatic environments.
Objective:
The aim of this research is to assess the control of MH in an aquatic environment by analyzing the usability of two tourniquet models with different adjustment mechanisms: windlass rod versus ratchet.
Methodology:
A pilot simulation study was conducted using a randomized crossover design to assess the control of MH resulting from an upper extremity arterial perforation in an aquatic setting. A sample of 24 trained lifeguards performed two randomized tests: one using a windlass-based Combat Application Tourniquet 7 Gen (T-CAT) and the other using a ratchet-based OMNA Marine Tourniquet (T-OMNA) specifically designed for aquatic use on a training arm for hemorrhage control. The tests were conducted after swimming an approximate distance of 100 meters and the tourniquets were applied while in the water. The following parameters were recorded: time of rescue (rescue phases and tourniquet application), perceived fatigue, and technical actions related to tourniquet skills.
Results:
With the T-OMNA, 46% of the lifeguards successfully stopped the MH compared to 21% with the T-CAT (P = .015). The approach swim time was 135 seconds with the T-OMNA and 131 seconds with the T-CAT (P = .42). The total time (swim time plus tourniquet placement) was 174 seconds with the T-OMNA and 177 seconds with the T-CAT (P = .55). The adjustment time (from securing the Velcro to completing the manipulation of the windlass or ratchet) for the T-OMNA was faster than with the T-CAT (six seconds versus 19 seconds; P < .001; effect size [ES] = 0.83). The perceived fatigue was high, with a score of seven out of ten in both tests (P = .46).
Conclusions:
Lifeguards in this study demonstrated the ability to use both tourniquets during aquatic rescues under conditions of fatigue. The tourniquet with the ratcheting-fixation system controlled hemorrhage in less time than the windlass rod-based tourniquet, although achieving complete bleeding control had a low success rate.
Appropriateness of transmission-based precautions after positive result for a non-SARS-CoV-2 virus was evaluated. Most patients (77.2%) lacked appropriate precautions within 3 hours of virus detection; 36.9% remained without appropriate precautions during their stay. With recent cessation of universal masking, adherence to infection control best practices is needed to optimize safety.
We examine the Holocene loess record in the Heye Catchment on the margins of the Tibetan Plateau (TP) and China Loess Plateau (CLP) to determine: the region to which the Heye Catchment climate is more similar; temporal change in wind strength; and modification of the loess record by mass wasting and human activity. Luminescence and radiocarbon dating demonstrate loess deposited in two periods: >11–8.6 ka and <5.1 ka. The 8.6–5.1 ka depositional hiatus, which coincides with the Mid-Holocene Climatic Optimum, is more similar to the loess deposition cessation in the TP than to the loess deposition deceleration in the CLP. Grain-size analysis suggests the Heye loess is a mixture of at least three different grain-size distributions and that it may derive from multiple sources. A greater proportion of coarse sediments in the older loess may indicate stronger winds compared with the more recent depositional period. Gravel incorporated into younger loess most likely comes from bedrock exposed in slump scarps. Human occupation of the catchment, for which the earliest evidence is 3.4 ka, postdates the onset of slumping; thus the slumps may have created a livable environment for humans.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Elected pope in the wake of a rebellion, Eugenius III came to power as a relative unknown during a time of crisis. This book examines the controversial developments in papal justice and theological debate during his pontificate, his treatment of Cistercian monasteries, his relationships with France, Spain, and Rome, his work in the papal states, and the crusades. It offers a new view of an under-appreciated pope and the place of the church in a rapidly changing European society.
Bernard of Pisa (c.1080s–1153) was one of the most surprising of medieval popes. A native of Pisa, he was a canon of the cathedral chapter and vicedominus of his archdiocese before entering Clairvaux as a monk in 1138, and becoming abbot of the new Cistercian foundation of Tre Fontane, near Rome, in 1140. He was elected to the papal throne in 1145 as a relative unknown at a time of crisis, and spent much of his pontificate away from Rome. As the first Cistercian monk to become pope, his relationship with his former abbot Bernard of Clairvaux has often been seen as the keynote of his pontificate, and Bernard's preaching of the Second Crusade has tended to overshadow Eugenius's role in the design and execution of that expedition. Yet his years as pope saw important developments in the relationship between the papal office and royal authority, in the role of the papacy as a judicial office, and in papal crusading theory. They were also critical years in the history of Rome, and of the Cistercian congregation.
The studies presented in this book consider the many facets of Eugenius as pope, exploring his oversight of judicial practice; theological developments in his pontificate; his treatment of Cistercian monasteries and of constitutional developments in his order; his relationships with Crown and Church in France and Spain, and with Rome and the Romans; his work in building up the papal states, and his view of the crusades in both the Baltic and the Mediterranean. Together these essays offer a new view not only of an under-appreciated pope but also of the institution he headed and of its place in a rapidly changing European society.
Since the death of Thomas Bernhard in 1989, the literary reputation of this complex and unique writer has risen to the point that he is now regarded as a major European figure. Bernhard emerged in the 1960s as one of Austria's major writers, challenging the popularity of such established writers as Heinrich Böll and Günter Grass on the German literary scene. His idiosyncratic prose consists of a tragic-comic blend of themes such as suicide, madness, and isolation combined with highly satirical and histrionic invectives against culture, tradition, and society. As a skillful impresario of public scandals by means of verbal assaults upon Austrian elite culture, Bernhard also earned himself the epithet of Übertreibungskünstler (artist of exaggeration). In this art of cultural and political provocation Bernhard remains unmatched to the present day. This volume of essays provides contributions by well-known critics that examine the most salient aspects of Bernhard's work, offering insights into literary strategies and public themes that made Bernhard one of Europe's masters of modern prose and drama. Essays examine Bernhard's complex artistic sensibility, his impact on Austria's critical memory, his relation to the legacy of Austrian Jewish culture, his representative value as Austria's prime literary export, and his cosmopolitanism and its significance for the rapidly changing multicultural landscape of Europe. Matthias Konzett is Associate Professor of German at Yale University. He is the author of The Rhetoric of National Dissent in Thomas Bernhard, Peter Handke, and Elfriede Jelinek (Camden House, 2000).
Seed production from weeds that are missed by herbicide application can affect future weed populations and management decisions. It may be possible to expand the utility of computerized weed management decision aids to include an estimate of weed seed production resulting from selected treatments based on crop yield potential. Field studies were conducted in soybean near Columbia, MO, to determine whether weed control recommendations based on crop yield potential from a computerized weed management decision aid influence weed seed production in two soybean row spacings. At approximately 28 d after planting, weed densities and heights were entered into WeedSOFT® to generate a list of treatments ranked by predicted crop yields. Treatments included: (1) highest predicted crop yield in a glyphosate-resistant system, (2) highest predicted crop yield in a nonglyphosate-resistant system, (3) a 10% yield reduction, (4) a 20% yield reduction, and (5) an untreated control. These treatments were applied to soybean grown in 38- and 76-cm rows. Treatments that provided 90% or higher control of an individual species at 22 d after treatment usually produced less seed than untreated checks. Weed seed production based on early-season herbicide efficacy showed a linear relationship and was relatively predictable (r2 ≥ 0.52) for the predominant weed species. For less dominant weed species, weed seed production was not strongly correlated (r2 ≤ 0.27) to early-season herbicide efficacy but apparently influenced by control of other weed species. Narrow row spacing reduced giant foxtail biomass both years but did not reduce common ragweed and ivyleaf morningglory biomass. Narrow rows did not decrease giant foxtail, common ragweed, and ivyleaf morningglory seed production.
Field studies were conducted in 2000 and 2001 to evaluate corn yield-loss predictions generated by WeedSOFT, a computerized weed management decision aid. Conventional tillage practices were used to produce corn in 76-cm rows in Illinois, Indiana, Kansas, Michigan, Missouri, Nebraska, and Wisconsin. A total of 21 site-years from these seven states were evaluated in this study. At 4 wk after planting, weed densities and size, crop-growth stage, estimated weed-free yield, and environmental conditions at the time of application were entered into WeedSOFT to generate POST treatments ranked by percent maximum yield (PMY). POST treatments were chosen with yield losses ranging from 0 to 20%. Data were subjected to linear regression analysis by state and pooled over all states to determine the relationship between actual and predicted yield loss. A slope value equal to one implies perfect agreement between actual and predicted yield loss. Slope value estimates for Illinois and Missouri were equal to one. Actual yield losses were higher than the software predicted in Kansas and lower than predicted in Michigan, Nebraska, and Wisconsin. Slope value estimate from a data set containing all site years was equal to one. This research demonstrated that variability in yield-loss predictions occurred at sites that contained a high density of a single weed specie (>100/m2) regardless of its competitive index (CI); at sites with a predominant broadleaf weed with a CI greater than five, such as Palmer amaranth, giant ragweed, common sunflower, and common cocklebur; and at sites that experience moderate to severe drought stress.
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.
Despite growing interest in men's perinatal mental health, we still know
little about whether becoming a new father is associated with increases
in psychological distress.
Aims
To use prospective longitudinal data to investigate whether becoming a
first-time expectant (partner pregnant) and/or new father (child <1
year) is associated with increases in depression and anxiety.
Method
Men were aged 20–24 years at baseline (n = 1162). Levels
of depression and anxiety were measured at four time points over 12
years. Over this time, 88 men were expectant fathers, 108 men were new
fathers and 626 men remained non-fathers.
Results
Longitudinal mixed models showed no significant increase in depression or
anxiety as a function of expectant or new fatherhood, as compared with
pre-fatherhood levels.
Conclusions
Our findings suggest that, generally, expectant and new fathers are not
at greater risk of depression or anxiety. Future epidemiological research
should continue to identify men who are most (and least) at risk to focus
resources and assistance most effectively.