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Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.
Methods
Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12–17 and young adults, age 18–32).
Results
The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors.
Conclusions
Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.
The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain (${\sim}2.8\,\mbox{K Jy}^{-1}$) low-system temperature (${\sim}18\,\mbox{K at }20\,\mbox{cm}$) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar $\mbox{J}0737{-}3039\mbox{A}$, pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR $\mbox{J}0540{-}6919$, and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR $\mbox{J}2241{-}5236$ exhibits a jitter limit of $<4\,\mbox{ns h}^{-1}$ whilst timing of PSR $\mbox{J}1909{-}3744$ over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.
Neuroimaging studies in adults with borderline personality disorder (BPD) have reported alterations in frontolimbic areas, but cannot differentiate between alterations originating from disease and those occurring as side-effects of medication or other consequences of the disorder.
Objectives
To provide a clearer picture of the organic origins of BPD, the present study reduced such confounds by examining adolescents in the early stages of the disorder. It also examined the extent to which alterations associated with BPD are specific, or shared more broadly among other psychiatric disorders.
Methods
Sixty right-handed, female adolescents (14-18 years) participated. 20 had a DSM-IV diagnosis of BPD, 20 had a different DSM-IV defined psychiatric disorder, and 20 were healthy controls. All groups were matched for age and IQ. Images were analysed using voxel-based morphometry.
Results
No differences were found in limbic or white matter structures. Compared to healthy controls, adolescents with BPD displayed reduced gray matter in dorsolateral prefrontal cortex bilaterally and in left orbitofrontal cortex, but there were no significant differences in gray matter between BPD and other psychiatric patients. Like BPD patients, non-BPD psychiatric patients displayed significantly less gray matter in right dorsolateral prefrontal cortex compared to healthy controls.
Conclusions
These findings indicate that the prefrontal cortex is the earliest affected in the progression of BPD, but this does not distinguish it clearly from other psychiatric disorders. Alterations in limbic areas and white matter structures were not observed, but may play a later role in the progression of the illness.
Objective: White matter (WM) microstructural changes areincreasingly recognized as a mechanism of age-related cognitive differences.This study examined the associations between patterns of WM microstructure andcognitive performance on the University of California, San Francisco (UCSF)Brain Health Assessment (BHA) subtests of memory (Favorites), executivefunctions and speed (Match), and visuospatial skills (Line Orientation) within asample of older adults. Method: Fractional anisotropy (FA) in WMtracts and BHA performance were examined in 84 older adults diagnosed asneurologically healthy (47), with mild cognitive impairment (19), or withdementia (18). The relationships between FA and subtest performances wereevaluated using regression analyses. We then explored whether regional WMpredicted performance after accounting for variance explained by global FA.Results: Memory performance was associated with FA of thefornix and the superior cerebellar peduncle; and executive functions and speed,with the body of the corpus callosum. The fornix–memory association andthe corpus callosum–executive association remained significant afteraccounting for global FA. Neither tract-based nor global FA was associated withvisuospatial performance. Conclusions: Memory and executivefunctions are associated with different patterns of WM diffusivity. Findings addinsight into WM alterations underlying age- and disease-related cognitivedecline.
The majority of fast radio bursts (FRBs) are poorly localised, hindering their potential scientific yield as galactic, intergalactic, and cosmological probes. LOFT-e, a digital backend for the U.K.’s e-MERLIN seven-telescope interferometer will provide commensal search and real-time detection of FRBs, taking full advantage of its field of view (FoV), sensitivity, and observation time. Upon burst detection, LOFT-e will store raw data offline, enabling the sub-arcsecond localisation provided by e-MERLIN and expanding the pool of localised FRBs. The high-time resolution backend will additionally introduce pulsar observing capabilities to e-MERLIN.
PSR B1820–30A is located in the globular cluster NGC 6624 and has the smallest projected distance to the centre of any globular cluster in the sky plane. We observe this millisecond pulsar over more than 25 years and obtain higher-order rotational frequency time derivative measurements through high-precision timing. Modelling these higher-order derivatives as being due to orbital motion, we find that the pulsar is in either a low-eccentricity smaller orbit with a low mass companion or a high-eccentricity larger orbit with a massive companion. The cluster mass properties and the observed properties of other nearby sources indicate that the high-eccentricity solution is more probably. This reveals that the pulsar is orbiting around an intermediate-mass black hole (IMBH) of mass >7500 M⊙ located at the cluster centre. This contribution is based on previous work published in MNRAS 471, 1258 (2017).
An evolution of the low-frequency pulse profile of PSR B2217+47 is observed during a six-year observing campaign with the LOFAR telescope at 150 MHz. The evolution is manifested as a new component in the profile trailing the main peak. The leading part of the profile, including a newly-observed weak component, is steady during the campaign. The transient component is not visible in simultaneous observations at 1500 MHz using the Lovell telescope, implying a chromatic effect. A variation in the dispersion measure of the source is detected in the same timespan. Precession of the pulsar and changes in the magnetosphere are investigated to explain the profile evolution. However, the listed properties favour a model based on turbulence in the interstellar medium (ISM). This interpretation is confirmed by a strong correlation between the intensity of the transient component and main peak in single pulses. Since PSR B2217+47 is the fourth brightest pulsar visible to LOFAR, we speculate that ISM-induced pulse profile evolution might be relatively common but subtle and that SKA-Low will detect many similar examples. In this scenario, similar studies of pulse profile evolution could be used in parallel with scintillation arcs to characterize the properties of the ISM.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
Methods
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Results
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Conclusions
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Infection prevention in electrophysiology (EP) laboratories is poorly characterized; thus, we conducted a cross-sectional survey using the SHEA Research Network. We found limited uptake of basic interventions, such as surveillance and appropriate peri-procedural antimicrobial use. Further study is needed to identify ways to improve infection prevention in this setting.
Hypoxic-ischemic encephalopathy (HIE) caused by fetal and perinatal asphyxia is an important cause of mortality in the neonatal period. Not only will asphyxia affect the brain but also other organs such as the liver and kidneys. Interestingly, it has been shown that liver damage is proportional to the severity of the asphyctic insult, implying an association between liver impairment and HIE. Accordingly, we investigated in an established rat model the acute and chronic hepatic response to both fetal (FA) and perinatal asphyxia (PA). In addition, we assessed whether fetal asphyctic preconditioning (PC) would have any beneficial effect on the liver. Inflammation, ceramide signaling and hepatocellular damage were analyzed in the livers of newborn and adult rats at several short- and long-term time points after both FA and PA. We found that although FA induced an acute inflammatory response, apoptotic mRNA levels and oxidative DNA damage were decreased at 96 h post FA. Whereas increased IL-6 and IL-10 mRNA levels were observed after PA, the combination of FA and PA (PC) attenuated the inflammatory response. Moreover, 6 h after PA anti-apoptotic genes were downregulated and associated with less lipid peroxidation, while preconditioned animals were comparable to controls. In summary, asphyctic PC seems to have an acute protective effect on the liver by modulating the inflammatory, apoptotic and anti-oxidative response. More insight into the hepatic response to asphyxia is necessary, as disturbed hepatic function is associated with metabolic diseases in later life.
Radio pulsars in relativistic binary systems are unique tools to study the curved space-time around massive compact objects. The discovery of a pulsar closely orbiting the super-massive black hole at the centre of our Galaxy, Sgr A⋆, would provide a superb test-bed for gravitational physics. To date, the absence of any radio pulsar discoveries within a few arc minutes of Sgr A⋆ has been explained by one principal factor: extreme scattering of radio waves caused by inhomogeneities in the ionized component of the interstellar medium in the central 100 pc around Sgr A⋆. Scattering, which causes temporal broadening of pulses, can only be mitigated by observing at higher frequencies. Here we describe recent searches of the Galactic centre region performed at a frequency of 18.95 GHz with the Effelsberg radio telescope.
Coral reef ecosystems have great importance for the countries of the Wider Caribbean Region in terms of both use and non-use values and services. Several of the contributors to this symposium attest to their importance for fisheries and biodiversity (see Ehrhardt et al. in Chapter 11; Appeldoorn in Chapter 10; Appeldoorn et al. in Chapter 12; Horrocks et al. in Chapter 9). Coral reef ecosystems support livelihoods (see McConney and Salas in Chapter 7) and provide critical ecosystem services (Schuhmann et al. in Chapter 8) including for tourism, although this aspect of their value is not developed in detail in Chapter 8. Caribbean coral reef ecosystems have been degraded by many human impacts of both marine and land-based origin (see Sweeney and Corbin in Chapter 4; Gil and Wells in Chapter 5; Yáñez-Arancibia et al. in Chapter 17). They are among the most complex and biologically diverse marine ecosystems, and will require a holistic ecosystem- based approach for their conservation and sustainable use.
This synthesis chapter presents the outputs of a group process aimed at developing a vision and way ahead for ecosystem-based management (EBM) for coral reef ecosystems in the Wider Caribbean, using the methods described earlier (Fanning et al. in Chapter 1). The chapter first describes a vision for coral reef EBM and reports on the priorities assigned to the identified vision elements. It then discusses how the vision might be achieved by taking into account assisting factors (those that facilitate achievement) and resisting factors (those that inhibit achievement). The chapter concludes with guidance on the strategic direction needed to implement the vision, identifying specific actions to be undertaken for each of the vision elements.
The Vision
The occupational breakdown of members of the Coral Reef Ecosystems Working Group reflected the diversity of affiliations present at the EBM Symposium and included governmental, intergovernmental, academic, non-governmental and private sector (fishers and fishing industry and consulting) representatives. With guidance provided by the facilitator, this diverse group of participants was asked to first address the question of “What do you see in place in 10 years’ time when EBM/EAF has become a reality in the Caribbean?”
Antenatal exposure of the fetus to inflammation may alter postnatal organ development. In our previous work, we demonstrated that the fetal liver is involved in the systemic inflammation associated with chorioamnionitis, leading to metabolic changes. On the basis of these findings, we hypothesized that chorioamnionitis can lead to postnatal inflammation-related liver injury and disturbed lipid metabolism. Chorioamnionitis was induced in sheep by intra-amniotic injection of lipopolysaccharide (LPS) or saline at 90, 100 and 110 days of gestation. Liver homeostasis and lipid metabolism were analyzed at term and at 7 weeks of age. At term, hepatic T-lymphocytes and apoptotic hepatocytes were increased. In addition, hepatic cholesterol and triglyceride levels were decreased in LPS-exposed animals compared with controls. At 7 weeks of age, no hepatic inflammation could be detected. However, liver triglycerides and plasma cholesterol levels were increased in LPS-exposed animals relative to controls. The changes in lipid levels at 7 weeks of age were associated with increased leptin receptor mRNA levels, increased lipid peroxidation, increased expression of cytochrome c oxidase subunit 4 as a marker for mitochondrial function and increased circulating ceramide levels. These findings demonstrate that chorioamnionitis-mediated antenatal inflammation-related liver disturbances have long-lasting postnatal effects on lipid metabolism.
Within the Herschel key project “The Warm And Dense ISM” (WADI) we systematically observea number of prominent photon-dominated regions (PDRs) to measure the impact of varying UVfields on the energy balance, the chemical and dynamical structure of heated molecularclouds.
Within the key project “Herschel M 33 extended survey” (HerM33es), we are studying the physical and chemical processes driving star formation and galactic evolution in the nearby galaxy M 33, combining the study of local conditions affecting individual star formation with properties only becoming apparent on global scales. Here, we present recent results obtained by the HerM33es team. Combining Spitzer and Herschel data ranging from 3.6 μm to 500μm, along with H i, Hα, and GALEX UV data, we have studied the dust at high spatial resolutions of 150 pc, providing estimators of the total infrared (TIR) brightness and of the star formation rate. While the temperature of the warm dust at high brightness is driven by young massive stars, evolved stellar populations appear to drive the temperature of the cold dust. Plane-parallel models of photon dominated regions (PDRs) fail to reproduce fully the [C ii], [O i], and CO maps obtained in a first spectroscopic study of one 2′ × 2′ subregion of M 33, located on the inner, northern spiral arm and encompassing the H ii region BCLMP 302.
We report the analysis of the mid-infrared spectral maps observed by Spitzer/IRS toward star-forming regions where the Herschel key program WADI has observed / will observe with HIFI and PACS. The IRS spectra are fitted using 4 components of small grains: PAH0, PAH+, PAHx, and evaporating VSG, and the spatial distributions of these components are derived.
We present results from the Herschel and IRAM projects to map M33 in the dust continuum and main emission lines, particularly C[II] and CO. The temperature of the cool dust decreases with distance from the center of M33 from ~25K to ~13K. The CO emission generally follows the dust temperature and the overall dust emission. However, about 1/6 of the molecular clouds are not associated with massive stars, such that about 1/6th the lifetime of an entity identifiable as a molecular cloud is in a pre-star formation state. These clouds are less CO-bright than those with massive stars. The largest sample of molecular clouds currently available for an external galaxy shows that the cloud CO luminosity function, usually viewed as the cloud H2 mass, steepens with radius such that smaller clouds are more numerous in the outer parts. The observations of the C[II] line with Herschel indicate that the C[II] emission traces on-going star formation rather than the neutral gas. This identification will be tested via velocity-resolved Herschel/HIFI C[II] spectra in the near future.