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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.
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).
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.
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.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Isolated aortic regurgitation and myocardial infarction are a rare congenital defect among neonatal patients. We present a case of a neonate with an unusual aortic valve morphology causing both regurgitation and obstruction of the left coronary artery ostium. Despite both non-invasive and invasive imaging modalities, accurate diagnosis of the valve morphology was only determined by direct visualisation at the time of surgical repair. To the knowledge of authors, this particular aortic valve morphology in neonatal population has not been previously reported in the literature.
Predictive associations were estimated between socioemotional dispositions measured at 10–17 years using the Child and Adolescent Dispositions Scale (CADS) and future individual differences in white matter microstructure measured at 22–31 years of age. Participants were 410 twins (48.3% monozygotic) selected for later neuroimaging by oversampling on risk for psychopathology from a representative sample of child and adolescent twins. Controlling for demographic covariates and total intracranial volume (TICV), each CADS disposition (negative emotionality, prosociality, and daring) rated by one of the informants (parent or youth) significantly predicted global fractional anisotropy (FA) averaged across the major white matter tracts in brain in adulthood, but did so through significant interactions with sex after false discovery rate (FDR) correction. In females, each 1 SD difference in greater parent-rated prosociality was associated with 0.43 SD greater FA (p < 0.0008). In males, each 1 SD difference in greater parent-rated daring was associated with 0.24 SD lower FA (p < 0.0008), and each 1 SD difference in greater youth-rated negative emotionality was associated with 0.18 SD greater average FA (p < 0.0040). These findings suggest that CADS dispositions are associated with FA, but associations differ by sex. Exploratory analyses suggest that FA may mediate the associations between dispositions and psychopathology in some cases. These associations over 12 years could reflect enduring brain–behavior associations in spite of transactions with the environment, but could equally reflect processes in which dispositional differences in behavior influence the development of white matter. Future longitudinal studies are needed to resolve the causal nature of these sex-moderated associations.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
Studies were conducted in a stale field production system in 2012 and 2013 to determine the effect of herbicide timing on Palmer amaranth control and ‘Covington’ sweetpotato yield and quality. Treatments consisted of flumioxazin at 72, 90, or 109 g ai ha−1 applied 45 d before transplanting (DBT) or 1 DBT, or sequentially the same rate at 45 DBT followed by (fb) 1 DBT; flumioxazin 109 g ha−1 applied 1 DBT fb S-metolachlor (800 g ai ha−1) at 0, 6 (± 1), or 10 d after treatment (DAT); flumioxazin at 72, 90, or 109 g ha−1 plus clomazone (630 g ai ha−1) applied 45 DBT fb S-metolachlor (800 g ha−1) applied 10 DAT; and fomesafen alone at 280 g ai ha−1 applied 45 DBT. Nontreated weed-free and weedy controls were included for comparison. Flumioxazin application time had a significant effect on Palmer amaranth control and sweetpotato yields, and the effect of flumioxazin rate was not significant. Treatments consisting of sequential application of flumioxazin 45 DBT fb 1 DBT or flumioxazin plus clomazone 45 DBT fb S-metolachlor 10 DAT provided the maximum Palmer amaranth control and sweetpotato yields (jumbo, No. 1, jumbo plus No. 1, marketable) among all treatments. Delayed flumioxazin application timings until 1 DBT allowed Palmer amaranth emergence on stale seedbeds and resulted only in 65, 62, 48, and 17% control at 14, 32, 68, and 109 DAT, respectively. POST transplant S-metolachlor applications following flumioxazin 1 DBT did not improve Palmer amaranth control, because the majority of Palmer amaranth emerged prior to S-metolachlor application. A control program consisting of flumioxazin 109 g ha−1 plus clomazone 630 g ha−1 at 45 DBT fb S-metolachlor 800 g ha−1 at 0 to 10 DAT provides an effective herbicide program for Palmer amaranth control in stale seedbed production systems in North Carolina sweetpotato.
Modern crinoids are dominated by the comatulids (unstalked forms) which range from the intertidal to abyssal depths. Modern stalked crinoids are restricted to depths greater than about 100 m. In the geologic past some stalked crinoids lived at depths of a few tens of meters or less in reef and bank environments. The primary vehicles postulated for the post-Triassic radiation of comatulids are lack of permanent fixation to the substratum and the capacity for mobility. Development of complex muscular articulations has enabled crawling or swimming which serve in habitat selection and avoidance of stress and predators. These and other adaptations may have bestowed on comatulids a higher survival capacity in shallow-water environments compared to stalked crinoids. Modern stalked crinoids lack mobility and complex behavioral adaptations seen in comatulids. Possibly, stalked crinoids in shallow water were unable to cope with the radiation of abundant, predaceous bony fishes in the late Mesozoic and became restricted to greater depths while the more adaptable comatulids gained ascendancy in shallow water.
The Mississippian Fort Payne Formation of Kentucky, Tennessee, and Alabama is well known for its abundant crinoids and a diverse array of autochthonous and allochthonous carbonate and siliciclastic facies. Using Principal Coordinate Analysis and Non-Metric Multidimensional Scaling, it is demonstrated that distinct, contemporaneous, and geographically adjacent autochthonous facies in south-central Kentucky supported distinct crinoid assemblages. The two carbonate buildup facies had different assemblages dominated by camerate crinoids, carbonate channel-fill deposits were dominated by advanced cladid crinoids and the camerate Elegantocrinus hemisphaericus, and green shale facies supported a fauna dominated by disparids and primitive cladid crinoids. Allochthonous facies contain neither distinctive nor exotic taxa. Thus, these transported assemblages are considered a mixture of elements from the recognized, autochthonous facies. Faunal assemblages from Dale Hollow Reservoir are allochthonous; and faunas in north-central Alabama and south-central Tennessee are different from others, which may reflect slight biogeographic distinctions.
Recurring associations of the trilobite ichnogenus Rusophycus with various “worm” burrows suggest an interaction between the two tracemakers, specifically, capture of the worm by the trilobite. An exceptional ichnofossil from the Upper Ordovician of southwestern Ohio shows characters consistent with previously described “trilobite hunting burrows” from Cambrian and Silurian strata. Preserved in convex hyporelief is R. carleyi, attributable to the trilobite Isotelus, on which is superimposed the case of a worm burrow of the ichnogenus Palaeophycus. The cast of the worm burrow appears to have been truncated by the digging activities of the trilobite, suggesting its predation of the worm. The exquisite preservation of ventral axial morphology of the trilobite distinguishes this Rusophycus from simpler bilobate forms attributable to filter-feeding behavior. Congruency in the preservation of worm and trilobite trace supports the conclusion that both were created at the same time, as the trilobite exited the intrastratal burrow. This is the first report of a trilobite hunting burrow from the Ordovician, and the first evidence for predatory behavior for the trilobite genus Isotelus.
A consensus conference on the reasons for the undertreatment of depression was organized by the National Depressive and Manic Depressive Association (NDMDA) on January 17–18,1996. The target audience included health policymakers, clinicians, patients and their families, and the public at large. Six key questions were addressed: (1) Is depression undertreated in the community and in the clinic? (2) What is the economic cost to society of depression? (3) What have been the efforts in the past to redress undertreatment and how successful have they been? (4) What are the reasons for the gap between our knowledge of the diagnosis and treatment of depression and actual treatment received in this country? (5) What can we do to narrow this gap? (6) What can we do immediately to narrow this gap?
Several studies demonstrating that central line–associated bloodstream infections (CLABSIs) are preventable prompted a national initiative to reduce the incidence of these infections.
We conducted a collaborative cohort study to evaluate the impact of the national “On the CUSP: Stop BSI” program on CLABSI rates among participating adult intensive care units (ICUs). The program goal was to achieve a unit-level mean CLABSI rate of less than 1 case per 1,000 catheter-days using standardized definitions from the National Healthcare Safety Network. Multilevel Poisson regression modeling compared infection rates before, during, and up to 18 months after the intervention was implemented.
A total of 1,071 ICUs from 44 states, the District of Columbia, and Puerto Rico, reporting 27,153 ICU-months and 4,454,324 catheter-days of data, were included in the analysis. The overall mean CLABSI rate significantly decreased from 1.96 cases per 1,000 catheter-days at baseline to 1.15 at 16–18 months after implementation. CLABSI rates decreased during all observation periods compared with baseline, with adjusted incidence rate ratios steadily decreasing to 0.57 (95% confidence intervals, 0.50–0.65) at 16–18 months after implementation.
Coincident with the implementation of the national “On the CUSP: Stop BSI” program was a significant and sustained decrease in CLABSIs among a large and diverse cohort of ICUs, demonstrating an overall 43% decrease and suggesting the majority of ICUs in the United States can achieve additional reductions in CLABSI rates.