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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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
Neonatal sepsis is a major cause of death and disability in newborns. Commonly used biomarkers for diagnosis and evaluation of treatment response lack sufficient sensitivity or specificity. Additionally, new targets to treat the dysregulated immune response are needed, as are methods to effectively screen drugs for these targets. Available research methods have hitherto not yielded the breakthroughs required to significantly improve disease outcomes, we therefore describe the potential of zebrafish (Danio rerio) larvae as preclinical model for neonatal sepsis. In biomedical research, zebrafish larvae combine the complexity of a whole organism with the convenience and high-throughput potential of in vitro methods. This paper illustrates that zebrafish exhibit an immune system that is remarkably similar to humans, both in terms of types of immune cells and signaling pathways. Moreover, the developmental state of the larval immune system is highly similar to human neonates. We provide examples of zebrafish larvae being used to study infections with pathogens commonly causing neonatal sepsis and discuss known limitations. We believe this species could expedite research into immune regulation during neonatal sepsis and may hold keys for the discovery of new biomarkers and novel treatment targets as well as for screening of targeted drug therapies.
Dirofilaria immitis is a parasitic nematode that survives in the circulatory system of suitable hosts for many years, causing the most severe thromboembolisms when simultaneous death of adult worms occurs. The two main mechanisms responsible for thrombus formation in mammals are the activation and aggregation of platelets and the generation of fibrin through the coagulation cascade. The aim of this work was to study the anticoagulant potential of excretory/secretory antigens from D. immitis adult worms (DiES) on the coagulation cascade of the host. Anticoagulant and inhibition assays respectively showed that DiES partially alter the coagulation cascade of the host and reduce the activity of the coagulation factor Xa, a key enzyme in the coagulation process. In addition, a D. immitis protein was identified by its similarity to the homologous serpin 6 from Brugia malayi as a possible candidate to form an inhibitory complex with FXa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and mass spectrometry. These results indicate that D. immitis could use the anticoagulant properties of its excretory/secretory antigens to control the formation of blood clots in its immediate intravascular habitat as a survival mechanism.
Over recent decades, biomass gains in remaining old-growth Amazonia forests have declined due to environmental change. Amazonia’s huge size and complexity makes understanding these changes, drivers, and consequences very challenging. Here, using a network of permanent monitoring plots at the Amazon–Cerrado transition, we quantify recent biomass carbon changes and explore their environmental drivers. Our study area covers 30 plots of upland and riparian forests sampled at least twice between 1996 and 2016 and subject to various levels of fire and drought. Using these plots, we aimed to: (1) estimate the long-term biomass change rate; (2) determine the extent to which forest changes are influenced by forest type; and (3) assess the threat to forests from ongoing environmental change. Overall, there was no net change in biomass, but there was clear variation among different forest types. Burning occurred at least once in 8 of the 12 riparian forests, while only 1 of the 18 upland forests burned, resulting in losses of carbon in burned riparian forests. Net biomass gains prevailed among other riparian and upland forests throughout Amazonia. Our results reveal an unanticipated vulnerability of riparian forests to fire, likely aggravated by drought, and threatening ecosystem conservation at the Amazon southern margins.
Arcuate fold-and-thrust belts have been extensively studied in the literature. Less attention, however, has been paid to the characteristics of local-scale arcuate structures, meaning 5–10 km long fold or thrust traces that display map-view curvature. Nevertheless, detailed investigation of small arcuate structures hosted in major arcs can contribute to understanding the pervasiveness of deformation mechanisms. We performed a combined geological and palaeomagnetic study on 21 sites from a c. 60 km2 area in the Northern Apennines in order to analyse minor arcs at a kilometric scale. As evidenced by the geological and structural analysis performed on the 21 sites, the fold axial trend changes from N–S to NW–SE in the study area. The comparison with palaeomagnetic results shows the lack of correlation between vertical axis rotations and fold axial trends. As a consequence, the minor arcuate shapes of thrusts and related folds are interpreted as mostly primary features inherited from the geometry of the palaeomargin, represented by pre-orogenic faults, according to a context of inversion tectonics.
Cygnus OB2 is a rich and relatively close (d~1.4 kpc) OB association in our Galaxy. It represents an ideal testbed for our theories about self-enrichment processes produced by pollution of the interstellar medium by successive generations of massive stars. Comerón & Pasquali (2012, A&A, 543, A101) found a correlation between the age of young stellar groups in Cygnus OB2 and their Galactic longitude. If is associated with a chemical composition gradient, it could support these self-enrichment processes.
The degree of development and operability of the indicators for the Marine Strategy Framework Directive (MSFD) using Descriptor 1 (D1) Biological Diversity was assessed. To this end, an overview of the relevance and degree of operability of the underlying parameters across 20 European countries was compiled by analysing national directives, legislation, regulations, and publicly available reports. Marked differences were found between countries in the degree of ecological relevance as well as in the degree of implementation and operability of the parameters chosen to indicate biological diversity. The best scoring EU countries were France, Germany, Greece and Spain, while the worst scoring countries were Italy and Slovenia. No country achieved maximum scores for the implementation of MSFD D1. The non-EU countries Norway and Turkey score as highly as the top-scoring EU countries. On the positive side, the chosen parameters for D1 indicators were generally identified as being an ecologically relevant reflection of Biological Diversity. On the negative side however, less than half of the chosen parameters are currently operational. It appears that at a pan-European level, no consistent and harmonized approach currently exists for the description and assessment of marine biological diversity. The implementation of the MSFD Descriptor 1 for Europe as a whole can therefore at best be marked as moderately successful.
SHARK is a proposal aimed at investigating the technical feasibility and the scientific capabilities of high-contrast cameras to be implemented at the Large Binocular Telescope (LBT). SHARK foresees two separated channels: near-infrared (NIR) channel and visible, both providing imaging and coronagraphic modes. We describe here the SHARK instrument concept, with particular emphasis on the NIR channel at the level of a conceptual study, performed in the framework of the call for proposals for new LBT instruments. The search for giant extra-Solar planets is the main science case, as we will outline in the paper.
We report on the EPICA Dronning Maud Land (East Antarctica) deep drilling operation. Starting with the scientific questions that led to the outline of the EPICA project, we introduce the setting of sister drillings at NorthGRIP and EPICA Dome C within the European ice-coring community. The progress of the drilling operation is described within the context of three parallel, deep-drilling operations, the problems that occurred and the solutions we developed. Modified procedures are described, such as the monitoring of penetration rate via cable weight rather than motor torque, and modifications to the system (e.g. closing the openings at the lower end of the outer barrel to reduce the risk of immersing the drill in highly concentrated chip suspension). Parameters of the drilling (e.g. core-break force, cutter pitch, chips balance, liquid level, core production rate and piece number) are discussed. We also review the operational mode, particularly in the context of achieved core length and piece length, which have to be optimized for drilling efficiency and core quality respectively. We conclude with recommendations addressing the design of the chip-collection openings and strictly limiting the cable-load drop with respect to the load at the start of the run.
The Magellan Adaptive Optics (MagAO) system saw first light in November 2012 at Las Campanas Observatory (LCO) on the 6.5m Clay telescope. Here we present an introduction to MagAO's visible wavelength diffraction limited imager, VisAO. VisAO delivers Strehl ratios greater than 30% from 0.62 microns (r') through 1 micron, where Strehl is even higher, and achieved resolutions as small as 20 milli-arcseconds. We took advantage of the excellent performance of MagAO/VisAO to conduct high contrast observations of an exoplanet in the optical. With VisAO, we are, for the first time, able to begin characterizing exoplanet atmospheres in the optical from the ground.
MagAO is the newly-commissioned adaptive optics (AO) instrument on the Magellan Clay telescope at Las Companas Observatory, Chile. MagAO has two co-mounted science cameras: VisAO for visible-light direct and spectral-differential imaging; and Clio for near to thermal IR direct imaging, non-redundant-mask interference, and prism spectroscopy. We demonstrate MagAO's simultaneous visible and infrared AO performance via direct images of exoplanet Beta Pictoris b. The planet was detected in 5 passbands from 0.9–5μm. Here we show the infrared images; the visible observations are presented in Males et al. 2013. MagAO is the first AO system to offer good performance with extensive coverage across the O/IR spectrum and thus offers an unprecedented opportunity to study the spectral energy distributions of directly-imaged extrasolar planetary atmospheres.
A series of editorials in this Journal have argued that psychiatry is in the midst of a crisis. The various solutions proposed would all involve a strengthening of psychiatry's identity as essentially ‘applied neuroscience’. Although not discounting the importance of the brain sciences and psychopharmacology, we argue that psychiatry needs to move beyond the dominance of the current, technological paradigm. This would be more in keeping with the evidence about how positive outcomes are achieved and could also serve to foster more meaningful collaboration with the growing service user movement.
To investigate an outbreak of healthcare-associated Burkholderia cepacia complex (BCC) primary bloodstream infections (BCC-BSI).
Design and Setting.
Case-crossover study in a public hospital, a university hospital and a private hospital in Rio de Janeiro, Brazil, from March 2006 to May 2006.
Twenty-five patients with BCC-BSI.
After determining the date BCC-BSI symptoms started for each patient, 3 time intervals of data collection were defined, each one with a duration of 3 days: the case period, starting just before BCC-BSI symptoms onset; the control period, starting 6 days before BCC-BSI symptoms onset; and the washout period, comprising the 3 days between the case period and the control period. Exposures evaluated were intravascular solutions and invasive devices and procedures. Potential risk factors were identified by using the McNemar χ2 adjusted test. Cultures of samples of potentially contaminated solutions were performed. BCC strain typing was performed by pulsed-field gel electrophoresis using Spel.
The statistical analysis revealed that the use of bromopride and dipyrone was associated with BCC-BSI. A total of 21 clinical isolates from 17 (68%) of the 25 patients and an isolate obtained from the bromopride vial were available for strain typing. Six pulsotypes were detected. A predominant pulsotype (A) accounted for 11 isolates obtained from 11 patients (65%) in the 3 study hospitals.
Our investigation, using a case-crossover design, of an outbreak of BCC-BSI infections concluded it was polyclonal but likely caused by infusion of contaminated bromopride. The epidemiological finding was validated by microbiological analysis. After recall of contaminated bromopride vials by the manufacturer, the outbreak was controlled.
Knowledge about harbour porpoise and bottlenose dolphin occurrence in Cardigan Bay Special Area of Conservation (SAC), Wales, is limited to daylight hours during summer, when conditions are suitable for traditional visual surveys. T-PODs are autonomous instruments programmed to log time-cues of species-specific echolocation signals for long periods of time. Here we investigated bottlenose dolphin and harbour porpoise habitat use and partitioning by deploying ten calibrated T-PODs in Cardigan Bay SAC for one year. The T-PODs detected both species all year round with a peak of detections in April–October for dolphins and in October–March for porpoise, revealing a previously unknown importance of the place to harbour porpoise during winter. Though the two species are sympatric, simultaneous detections of both species were rare and indication of temporal habitat partitioning between the two species in some parts of the SAC was observed. The one location where simultaneous detections were not as rare was close to the stretch of shoreline where stranding of porpoises killed by dolphins are most common, suggesting that the observed spatiotemporal overlap leads to inter-specific interactions, in some cases fatal for the porpoise.