Molecular Targets of Psychedelics and Their Role in Behavioral Models of Hallucinogenic Action

Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in both rats and humans, attempts to translate this behavior to mice are rare. In contrast to prior gene knockout studies suggesting the mGluR2 is necessary for 5-HT2A agonist-induced HTR, mGluR2 knockout (Grm2-/-) mice still displayed HTR upon administration of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). Additionally, DOI and lysergic acid diethylamide (LSD) produced unexpected improvements in PPI in male 126S6/Sv wild-type mice, depending on the experimental protocol used and the origin of the animals. Sex differences were observed as DOI-induced improvements in PPI were present in female 129S6/Sv mice of the same origin and tested with the same protocol as their male counterparts; this effect in females was absent in 5-HT2A knockout (Htr2a-/-) mice. The results of this study shed light on issues with replicability and reproducibility in science, the importance of highlighting the origin and background of animal subjects, and potential sex differences in hallucinogenic drug action

Neural mechanisms of response-preparation and inhibition in bilingual and monolingual children: Lateralized Readiness Potentials (LRPs) during a nonverbal Stroop task

Inhibitory control is a core executive function (EF) skill, thought to involve cognitive 'interference suppression' and motor 'response inhibition' sub-processes. A few studies have shown that early bilingualism shapes interference suppression but not response inhibition skills, however current behavioral measures do not fully allow us to disentangle these subcomponents. Lateralized Readiness Potentials (LRPs) are centroparietal event-related potentials (ERPs) that track motor response-preparations between stimulus-presentation and behavioral responses. We examine LRPs elicited during successful inhibitory control on a nonverbal Stroop task, in 6-8 year-old bilingual (n = 44) and monolingual (n = 48) children from comparable socio-economic backgrounds. Relative to monolinguals, bilinguals showed longer and stronger incorrect-response preparations, and a more mature pattern of correct-response preparation (shorter peak-latencies), underlying correct responses on Stroop-interference trials. Neural markers of response-inhibition were comparable between groups and no behavioral differences were found between-groups on the Stroop task. Results suggest group differences in underlying mechanisms of centroparietal motor-response preparation mechanisms in this age group, contrary to what has been shown using behavioral tasks previously. We discuss neural results in the context of speed-accuracy trade-offs. This is the first study to examine neural markers of motor-responses in bilingual children.Published versio

Negative Statements Considered Useful

Knowledge bases (KBs) about notable entities and their properties are an important asset in applications such as search, question answering and dialogue. All popular KBs capture virtually only positive statements, and abstain from taking any stance on statements not stored in the KB. This paper makes the case for explicitly stating salient statements that do not hold. Negative statements are useful to overcome limitations of question answering systems that are mainly geared for positive questions; they can also contribute to informative summaries of entities. Due to the abundance of such invalid statements, any effort to compile them needs to address ranking by saliency. We present a statisticalinference method for compiling and ranking negative statements, based on expectations from positive statements of related entities in peer groups. Experimental results, with a variety of datasets, show that the method can effectively discover notable negative statements, and extrinsic studies underline their usefulness for entity summarization. Datasets and code are released as resources for further research

Inequalities of harmonic univalent functions with connections of hypergeometric functions

Let SH be the class of functions f = h + (g) over bar that are harmonic univalent and sense-preserving in the open unit disk U = {z : vertical bar z vertical bar < 1} for which f(0) = f'(0) - 1 = 0. In this paper, we introduce and study a subclass H(alpha, beta)of the class SH and the subclass NH(alpha, beta) with negative coefficients. We obtain basic results involving sufficient coefficient conditions for a function in the subclass H(alpha, beta) and we show that these conditions are also necessary for negative coefficients, distortion bounds, extreme points, convolution and convex combinations. In this paper an attempt has also been made to discuss some results that uncover some of the connections of hypergeometric functions with a subclass of harmonic univalent functions

The Pervasive Crisis of Diminishing Radiation Therapy Access for Vulnerable Populations in the United States—Part 4: Appalachian Patients

Purpose: Compared with the rest of the United States, the population of Appalachia has lower education levels, higher rates of poverty, and limited access to health care. The presence of disparities in radiation therapy (RT) access for Appalachian patients with cancer has rarely been examined. Methods and materials: The National Cancer Institute initiatives toward addressing disparities in treatment access for rural populations were examined. An extensive literature search was undertaken for studies investigating RT access disparities in Appalachian patients, beginning with the most common cancers in these patients (lung, colorectal, and cervical). Results: Although the literature investigating RT access disparities in Appalachia is relatively sparse, studies examining lung, colorectal, cervical, prostate, head and neck, breast, and esophageal cancer, as well as lymphoma, indicate an unfortunate commonality in barriers to optimal RT access for Appalachian patients with cancer. These barriers are predominantly socioeconomic in nature (low income and lack of private insurance) but are exacerbated by paucities in both the number and quality of radiation centers that are accessible to this patient population. Conclusions: Regardless of organ system, there are significant barriers for Appalachian patients with cancer to receive RT. Such diminished access is alarming and warrants resources devoted to addressing these disparities, which often go overlooked because of the assumption that the overall wealth of the United States is tangibly applicable to all of its citizens. Without intelligently targeted investments of time and finances in this arena, there is great risk of exacerbating rather than alleviating the already heavy burden facing Appalachian patients with cancer

A New Inverse Rayleigh Distribution with Applications of COVID-19 Data: Properties, Estimation Methods and Censored Sample

This paper aims at modelling the COVID-19 spread in the United Kingdom and the United States of America, by specifying an optimal statistical univariate model. A new lifetime distribution with three-parameters is introduced by a combination of inverse Rayleigh distribution and odd Weibull family of distributions to formulate the odd Weibull inverse Rayleigh (OWIR) distribution. Some of the mathematical properties of the OWIR distribution are discussed as linear representation, quantile, moments, function of moment production, hazard rate, stress-strength reliability, and order statistics. Maximum likelihood, maximum product spacing, and Bayesian estimation method are applied to estimate the unknown parameters of OWIR distribution. The parameters of the OWIR distribution are estimated under the progressive type-II censoring scheme with random removal. A numerical result of a Monte Carlo simulation is obtained to assess the use of estimation methods

A New Inverse Rayleigh Distribution with Applications of COVID-19 Data: Properties, Estimation Methods and Censored Sample

This paper aims at modelling the COVID-19 spread in the United Kingdom and the United States of America, by specifying an optimal statistical univariate model. A new lifetime distribution with three-parameters is introduced by a combination of inverse Rayleigh distribution and odd Weibull family of distributions to formulate the odd Weibull inverse Rayleigh (OWIR) distribution. Some of the mathematical properties of the OWIR distribution are discussed as linear representation, quantile, moments, function of moment production, hazard rate, stress-strength reliability, and order statistics. Maximum likelihood, maximum product spacing, and Bayesian estimation method are applied to estimate the unknown parameters of OWIR distribution. The parameters of the OWIR distribution are estimated under the progressive type-II censoring scheme with random removal. A numerical result of a Monte Carlo simulation is obtained to assess the use of estimation methods

Psychotherapy as a treatment modality for psychiatric disorders: Perceptions of general public of Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>Psychiatric disorders affect about 450 million individuals worldwide. A number of treatment modalities such as psychotropic medications, psychotherapy and electroconvulsive therapy can be used to treat these disorders. Attitudes of general public play a pivotal role in effective utilization of mental health services. We explored the perceptions of general public of Karachi, Pakistan regarding psychotherapy.</p> <p>Methods</p> <p>A cross-sectional study was conducted in Karachi, Pakistan during July-August, 2008. A three-step sampling strategy and a structured questionnaire were employed to survey knowledge and perceptions of adult general public about psychotherapy. Descriptive statistics were used for baseline characteristics. Logistic regression models were used to investigate any significant associations between baseline characteristics of the participants and their perceptions.</p> <p>Results</p> <p>The study sample comprised of 985 individuals (536 males; 531 financially independent) with an average age of 36.7 years (SD 13.54 years) and 12.5 years (SD 3.09 years) of education were included. Majority (59.4%; n = 585) claimed to be aware of psychotherapy as a treatment option for psychiatric disorders but 47.5% of these (n = 278/585) failed to identify its correct definition. Concerns voiced by the participants about psychotherapy included stigma (48.7%) and breech in confidentiality (39.5%); 60.7% opined it cost effective and 86.5% favored its use as an adjuvant modality. A preference for psychotherapy as the treatment strategy for psychiatric disorders was demonstrated by 46.6% (n = 459/985). Younger, more educated, financially independent and female participants were more likely to prefer psychotherapy as were those who deemed it cost effective.</p> <p>Conclusion</p> <p>Positive attitudes regarding the acceptability, clinical utility and cost-effectiveness of psychotherapy were observed in a sample representative of general public of Karachi, Pakistan. These findings highlight its potential utility for devising pragmatic mental health strategies in the face of limited resources.</p