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Though theory suggests that individual differences in neuroticism (a tendency to experience negative emotions) would be associated with altered functioning of the amygdala (which has been linked with emotionality and emotion dysregulation in childhood, adolescence, and adulthood), results of functional neuroimaging studies have been contradictory and inconclusive. We aimed to clarify the relationship between neuroticism and three hypothesized neural markers derived from functional magnetic resonance imaging during negative emotion face processing: amygdala activation, amygdala habituation, and amygdala-prefrontal connectivity, each of which plays an important role in the experience and regulation of emotions. We used general linear models to examine the relationship between trait neuroticism and the hypothesized neural markers in a large sample of over 500 young adults. Although neuroticism was not significantly associated with magnitude of amygdala activation or amygdala habituation, it was associated with amygdala–ventromedial prefrontal cortex connectivity, which has been implicated in emotion regulation. Results suggest that trait neuroticism may represent a failure in top-down control and regulation of emotional reactions, rather than overactive emotion generation processes, per se. These findings suggest that neuroticism, which has been associated with increased rates of transdiagnostic psychopathology, may represent a failure in the inhibitory neurocircuitry associated with emotion regulation.
Combinatorial configurations may generally be phrased in terms of arrangements of objects into sets subject to certain conditions. In view of this, the question arises as to whether given a set S and its power-set Us (the class of all subsets of S), it might be possible to structure Us in a combinatorially significant manner. This paper proposes and investigates one such structuring achieved by defining a distance function over US.
Given A, B in Us, define their distance by
where N(E) denotes the number of elements in E, + ∞ being an admissible value.
Aripiprazole lauroxil (AL) is a long-acting injectable atypical antipsychotic that was evaluated for the treatment of schizophrenia in a randomized, placebo-controlled, Phase 3 study. Here, we present exploratory analyses of supportive efficacy endpoints.
Patients experiencing an acute exacerbation of schizophrenia received AL 441 mg intramuscularly (IM), AL 882 mg IM, or matching placebo IM monthly. Supportive endpoints included changes from baseline at subsequent time points in Clinical Global Impression-Severity (CGI-S) scale score; Positive and Negative Syndrome Scale (PANSS) Total score; PANSS Positive, Negative, and General Psychopathology subscale scores; PANSS Marder factors (post hoc); and PANSS responder rate. Overall response rate, based on PANSS Total score and Clinical Global Impression–Improvement (CGI-I) scale score, was also analyzed.
Of 622 patients who were randomized, 596 had ≥1 post-baseline PANSS score. Patients were markedly ill at baseline (mean PANSS Total scores 92–94). Compared with placebo, CGI-S scores; PANSS Positive, Negative, and General Psychopathology subscale scores; and PANSS Marder factors were all significantly (p<0.001) improved by Day 85 with both AL doses, with significantly lower scores starting from Day 8 in most instances. Treatment response rates were significantly (p<0.001) greater with both doses of AL vs placebo.
AL demonstrated robust efficacy on CGI-S score, PANSS subscale scores, PANSS Marder factors, and response rates. Study limitations included use of a fixed dose for initial oral aripiprazole and fixed monthly AL doses without the option to individualize the oral initiation dosing or injection frequency for efficacy, tolerability, or safety.
Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.
This study aimed to examine the effect of Hurricane Sandy on Long Island mental health emergency department (ED) visits and to determine whether these visits varied according to patient demographics or geographic area and intensity of the impact.
Individual-level de-identified data were extracted from the Statewide Planning and Research Cooperative System from New York State ED visits from October 1 to December 2012 for residents of Nassau and Suffolk counties in Long Island. The dates of the ED visits were grouped into 4 periods: (1) pre-Sandy, October 1–28; (2) during Sandy, October 29; (3) post-Sandy I, October 30 to November 1; and (4) post-Sandy II, November 2–30.
A total of 126,337 ED visits were recorded among 23 EDs. A significant drop in volume was observed on October 29; 399 more ED visits for physical health diagnoses were identified in the post-Sandy I period than in the pre-Sandy period. “Diseases of the respiratory system” was the only diagnosis group that showed a positive trend in the post-Sandy I period compared with the pre-Sandy period (increase of 4%). No significant changes in mental health visits were observed after Sandy landfall.
This analysis suggests that the critical temporal window during which ED resources should be increased is in the immediate aftermath of a hurricane. (Disaster Med Public Health Preparedness. 2016;10:344–350)
We previously reported an association between 5HTTLPR genotype and
outcome following cognitive–behavioural therapy (CBT) in child anxiety
(Cohort 1). Children homozygous for the low-expression short-allele
showed more positive outcomes. Other similar studies have produced mixed
results, with most reporting no association between genotype and CBT
To replicate the association between 5HTTLPR and CBT outcome in child
anxiety from the Genes for Treatment study (GxT Cohort 2,
n = 829).
Logistic and linear mixed effects models were used to examine the
relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both
cohorts were performed.
There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2.
Mega-analyses identified a significant association between 5HTTLPR and
remission from all anxiety disorders at follow-up (odds ratio 0.45,
P = 0.014), but not primary anxiety disorder
The association between 5HTTLPR genotype and CBT outcome did not
replicate. Short-allele homozygotes showed more positive treatment
outcomes, but with small, non-significant effects. Future studies would
benefit from utilising whole genome approaches and large, homogenous
On 14 August 2003, New York City and a large portion of the northeastern United States experienced the largest blackout in the history of the country. An analysis of such a widespread disaster on emergency medical service (EMS) operations may assist in planning for and managing such disasters in the future.
A retrospective review of all EMS activity within New York City's 9-1-1 emergency telephone system during the 29 hours during which all or parts of the city were without power (16:11 hours (h) on 14 August 2003 until 21:03 h on 15 August 2003) was performed. Control periods were established utilizing identical time periods during the five weeks preceding the blackout.
Significant increases were identified in the overall EMS demand (7,844 incidents vs. 3,860 incidents; p<0.001) as well as in 20 of the 62 calltypes of the system, including ca rd i ac arrests (119 vs.76, p= 0.043).Significant decreases were found only among calls related to psychological emergencies (114 vs. 221; p= 0.006) and drugor alcohol-related emergencies (78 vs. 146; p = 0.009). Though median response times increased by only 60 seconds, median call-processing times within the 9-1-1 emergency telephone system EMS dispatch center of the city increased from 1.1 to 5.5 minutes.
The citywide blackout resulted in dramatic changes in the demands upon the EMS system of New York City, the types of patients for whom EMS providers were assigned to provide care, and the dispositions for those assignments. During this time of increased, system-wide demand, the use of cross-trained firefighter and first-responder engine companies resulted in improved response times to cardiac arrest patients. Finally, the ability of the EMS dispatch center to process the increased requests for EMS assistance proved to be the rate-limiting step in responding to these emergencies.These findings will prove useful in planning for future blackouts or any disaster that may broadly impact the infrastructure of a city.
It has long been known that the most complex combinations of cardiac malformations are those found in the setting of the so-called “splenic syndromes”.1 Many aspects of these syndromes have been controversial over recent years, not least the presence or absence of features of isomerism within the heart.2,3 Recent experience with genetic manipulation of mice, nonetheless, has now shown that it is possible to generate unequivocal evidence of cardiac isomerism, particularly in those animals which show features of right isomerism when the genes responsible for morphologically leftness are knocked out.4 Furthermore, when the crucial philosophical principle known as the “morphological method”5 is applied to the hearts of patients known to have visceral heterotaxy, it is equally clear that patients falling within these groups, when judged on the extent of the pectinate muscles relative to the atrioventricular junctions, exhibit isomerism of either the morphologically right or left atrial appendages.3
Personality traits have been hypothesized to involve specific neurotransmitter systems. In order to test this model, the relationship between the responses to serotonergic and noradrenergic probes, central cerebrospinal fluid (CSF) measures of monoamine neurotransmitters and the Tridimensional Personality Questionnaire (TPQ) were evaluated in a cohort of personality disorder subjects.
A total of 142 patients meeting at least one personality disorder (meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition–Revised criteria) participated in these studies. The prolactin response to fenfluramine (a measure of serotonin function) was obtained for 110 subjects; growth hormone response to clonidine (a measure of noradrenergic function) was obtained for 77 subjects, while homovanillic acid (HVA) at baseline, an index of dopaminergic function, was available for 103 subjects. Measures of central neurotransmitter function (dopaminergic, serotonergic, and noradrenergic: HVA, 5-hydroxyindolacetic acid, and 3-methoxy-4-hydroxyphenylglycol, respectively) were available for 36 subjects. Separate regression analyses utilizing each of the hypothesized associations, where the TPQ total scores were used as the dependent measures and the biologic indices were the independent measures were conducted. Exploratory correlational analyses between these biologic measures and the four dimensions of the TPQ (and its subscales) were also conducted. (Correlations are reported if they would remain significant at P<.01 level after Bonferroni correction for multiple comparisons across the six neuroendocrine measures).
In the regression analyses, there was a trend association between CSF and plasma HVA in predicting novelty-seeking (P<.07). No other significant associations were found in the other three measures. Regarding the individual correlational analyses, the persistence scale of the TPQ was significantly positively correlated with the growth hormone response to clonidine (r=.30, P<.008). The sentimentality subscale (reward dependence) was positively correlated with CSF 5-hydroxyindolacetic acid (r=0.45, P<.001), while the attachment subscale (also reward dependence) was correlated with CSF 3-methoxy-4-hydroxyphenylglycol (r=0.49, P<.002).
Limited support was provided for a relationship between monoamines, particularly dopamine and novelty-seeking as well as norepinephrine and reward dependence but other hypothesized relationships were not supported by these measures.
RNase L and Ire1p are members of a superfamily of
regulated endoribonucleases that play essential roles
in mediating diverse types of cellular stress responses.
2′-5′ oligoadenylates, produced in response
to interferon treatment and viral double-stranded RNA,
are necessary to activate RNase L. In contrast, unfolded
proteins in the endoplasmic reticulum activate Ire1p, a
transmembrane serine/threonine kinase and endoribonuclease.
To probe their similarities and differences, molecular
properties of wild-type and mutant forms of human RNase
L and yeast Ire1p were compared. Surprisingly, RNase L
and Ire1p showed mutually exclusive RNA substrate specificity
and partially overlapping but not identical requirements
for phylogenetically conserved amino acid residues in their
nuclease domains. A functional model for RNase L was generated
based on the comparative analysis with Ire1p that assigns
novel roles for ankyrin repeats and kinase-like domains.
Sylvester  proposed the following question in 1893. If a finite set of points in a plane is such that on the line determined by any two points of the set there is always a third point of the set, is the set collinear? Equivalently, given a finite planar set of non-collinear points, does there exist a line containing exactly two of the points?
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