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Experimental results indicate that the proposed loss functions, applied to the MNIST and CelebA data sets, under both DCGAN and StyleGAN architectures, confer performance benefits by virtue of the extra degrees of freedom provided by the parameters k and α, respectively. More specifically, experiments show improvements with regard to the quality of the generated images as measured by the Fréchet inception distance score and training stability. While it was applied to GANs in this study, the proposed approach is generic and can be used in other applications of information theory to deep learning, for example, the issues of fairness or privacy in artificial intelligence.Human bipedalism entails relatively short strides compared with facultatively bipedal primates. Unique non-sagittal-plane motions associated with bipedalism may account for part of this discrepancy. Pelvic rotation anteriorly translates the hip, contributing to bipedal stride length (i.e. the 'pelvic step'). Facultative bipedalism in non-human primates entails much larger pelvic rotation than in humans, suggesting that a larger pelvic step may contribute to their relatively longer strides. We collected data on the pelvic step in bipedal chimpanzees and over a wide speed range of human walking. At matched dimensionless speeds, humans have 26.7% shorter dimensionless strides, and a pelvic step 5.4 times smaller than bipedal chimpanzees. Differences in pelvic rotation explain 31.8% of the difference in dimensionless stride length between the two species. We suggest that relative stride lengths and the pelvic step have been significantly reduced throughout the course of hominin evolution.Milgram empirically showed that people knowing only connections to their friends could locate any person in the U.S. in a few steps. Later research showed that social network topology enables a node aware of its full routing to find an arbitrary target in even fewer steps. Saracatinib ic50 Yet, the success of people in forwarding efficiently knowing only personal connections is still not fully explained. To study this problem, we emulate it on a real location-based social network, Gowalla. It provides explicit information about friends and temporal locations of each user useful for studies of human mobility. Here, we use it to conduct a massive computational experiment to establish new necessary and sufficient conditions for achieving social search efficiency. The results demonstrate that only the distribution of friendship edges and the partial knowledge of friends of friends are essential and sufficient for the efficiency of social search. Surprisingly, the efficiency of the search using the original distribution of friendship edges is not dependent on how the nodes are distributed into space. Moreover, the effect of using a limited knowledge that each node possesses about friends of its friends is strongly nonlinear. We show that gains of such use grow statistically significantly only when this knowledge is limited to a small fraction of friends of friends.

Although δ-9-tetrahydrocannabinol (THC), the main cannabinoid from the cannabis plant, is responsible for the psychotomimetic effects of cannabis, cannabidiol (CBD), the second most abundant cannabinoid in the cannabis plant, does not show any psychotomimetic effect. Cannabidiol has even been proposed to be antipsychotic and to counteract some of the psychotomimetic effects of THC. The aim of this study was to test the potential antipsychotomimetic effects of CBD.

Eighteen members from a cannabis social club were tested for subjective and psychotomimetic effects under the effects of different full-spectrum cannabis extracts containing either THC, CBD, THC + CBD, or placebo in a naturalistic, randomized, double-blind, crossover, placebo-controlled study.

Results showed that participants under the effects of THC + CBD showed lower psychotomimetic scores in subjective scales when compared with THC alone. Subjective scores were lower under the effects of CBD and placebo when compared with THC + CBD. Cannabiannabinoid system and psychotic-like symptoms and has important implications for the understanding of schizophrenia and the therapeutic potential of CBD as an antipsychotic. Lastly, we demonstrate how reliable methodologies can be implemented in real situations to collect valid ecological evidence outside classic laboratory settings.

The topic of patients' discontinuing use of antidepressants has received increasing attention. Patients and physicians can encounter challenges regarding the three major questions in the field of antidepressant discontinuation who can discontinue, what is the best time to discontinue; and what is the best method to discontinue.

This commentary summarizes the current state of the evidence related to antidepressant discontinuation.

There is limited evidence underlying the extremely relevant clinical topic of antidepressant discontinuation. It is poorly understood which patients, after response to antidepressants, benefit (most) from discontinuation. Moreover, established and validated markers of an individual's risk of relapse after antidepressant cessation are lacking, and non-sponsored discontinuation studies are rare. Many discontinuation studies do not distinguish between relapse and antidepressant discontinuation symptoms, and very few studies compared different discontinuation strategies, with none can guide evidence-based decision making in clinical practice.

Antidepressants are among the most frequently prescribed medications during pregnancy and may affect fetal weight. Associations between antenatal antidepressant use and ultrasonographic measures of fetal development have rarely been examined. We hypothesized that the prescription of an antenatal antidepressant would be associated with lower estimated fetal weight (EFW).

A retrospective analysis of routine ultrasonographic data extracted from electronic medical records was performed on a cohort of pregnant women with psychiatric diagnoses and grouped according to the presence of an antenatal antidepressant prescription (n = 32 antidepressant-prescribed and n = 44 antidepressant prescription-free). After stratifying for gestational age, comparisons included 13 ultrasonographic parameters, frequency of oligohydramnios and polyhydramnios and growth deceleration, and maternal serum protein markers assessed per routine care, including α-fetoprotein, free β-human chorionic gonadotropin, and unconjugated estriol h lower femur length and greater left ventricular diameter in mid-late gestation. Future research should examine the clinical implications of these findings.

Numerous health authority approvals of esketamine nasal spray, combined with oral antidepressant, to treat depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior were based on 2 identically designed, double-blind, phase 3 studies.

Across both ASPIRE studies (NCT03039192, NCT03097133), patients (N = 456) were randomized to esketamine 84 mg or placebo nasal spray twice weekly for 4 weeks plus comprehensive standard of care, including hospitalization and newly initiated or optimized antidepressant(s). In post hoc analyses of pooled data, changes from baseline at 24 hours after the first dose in Montgomery-Åsberg Depression Rating Scale total score and Clinical Global Impression-Severity of Suicidality-Revised, in the full cohort and in subgroups, were analyzed using analysis of covariance.

Esketamine plus standard of care demonstrated significantly greater improvement in Montgomery-Åsberg Depression Rating Scale total score versus placebo plus standard of care suicidal ideation or behavior, especially in those with a history of suicide attempt, providing a new treatment option for this particularly ill and vulnerable population.

To evaluate whether optical coherence tomography (OCT) can determine polypoidal lesion (PL) perfusion in polypoidal choroidal vasculopathy (PCV) eyes following 12-months of aflibercept monotherapy. PL perfusion status, assessed by indocyanine green angiography (ICGA), is an important anatomical outcome in PCV management.

Post-hoc data from a prospective randomised, open-label, study in eyes with PCV undergoing monotherapy with aflibercept evaluated PL perfusion status based on ICGA (gold standard) and OCT features from baseline to 12-months.

Individual PLs(110 in total) from 48 eyes(48 patients) showed at 12-months, 57/110 PLs(51.8%) were closed on ICGA. At 12-months, eyes with closed PLs were more likely to have the following OCT features 1)no SRF(67.1% versus 32.9%), 2)smaller PED height(67.2(±43.8) versus 189.2(±104.9)μm), 3)densely hyper-reflective PED contents(84.0% versus 16.0%), 4)an absence of a hyper-reflective ring(64.0% versus 36.0%) and a 5)indistinct overlying RPE(71.4% versus 28.6%) (all p<0.05). The three highest performing OCT features that differentiated perfused from closed PLs were (1), (3) and (4); (Area under the receiver operating characteristic curve[AUC-ROC] 0.85, 0.73, 0.70, respectively). A combination of these three features achieved an AUC-ROC of 0.90.

PL closure, an important anatomical treatment outcome in PCV typically defined by ICGA, can be accurately detected by specific OCT features.

PL closure, an important anatomical treatment outcome in PCV typically defined by ICGA, can be accurately detected by specific OCT features.

Evaluations from pharmacogenetics implementation programs at major US medical centers have reported variability in the clinical adoption of pharmacogenetics across therapeutic areas. A potential cause for this variability may involve therapeutic area-specific differences in published pharmacogenetics recommendations to clinicians. To date, however, the potential for differences in clinical pharmacogenetics recommendations by therapeutic areas from prominent US guidance sources has not been assessed. Accordingly, our objective was to comprehensively compare essential elements from clinical pharmacogenetics recommendations contained within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administration drug labels and clinical practice guidelines from US professional medical organizations across therapeutic areas.

We analyzed clinical pharmacogenetics recommendation elements within Clinical Pharmacogenetics Implementation Consortium guidelines, US Food and Drug Administrationn the basis of our results, we infer that observed differences in clinical pharmacogenetics recommendations across therapeutic areas may result from specific factors associated with individual disease states, the associated genetic biomarkers, and the characteristics of the organizations providing recommendations.Thiopurines [e.g. 6-mercaptopurine (6MP)] are essential for the cure of acute lymphoblastic leukemia (ALL) but can cause dose-limiting hematopoietic toxicity. Germline variants in drug-metabolizing enzyme genes TPMT and NUDT15 have been linked to the risk of thiopurine toxicity. However, the full spectrum of genetic polymorphism in these genes and their impact on the pharmacological effects of thiopurines remain unclear. Herein, we comprehensively sequenced the TPMT and NUDT15 genes in 685 children with ALL from the Children's Oncology Group AALL03N1 trial and evaluated their association with 6MP dose intensity. We identified 6 and 5 coding variants in TPMT and NUDT15 respectively, confirming the association at known pharmacogenetic variants. Importantly, we discovered a novel gain-of-function noncoding variants in TPMT associated with increased 6MP tolerance (rs12199316), with independent validation in 380 patients from the St. Jude Total Therapy XV protocol. Located adjacent to a regulatory DNA element, this intergenic variant was strongly associated TPMT transcription, with the variant allele linked to higher expression (P = 2.

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