Evaluation of QSAR and ligand enzyme docking for the identification of ABCB1 substrates

P-glycoprotein (P-gp) is an efflux pump that belongs to ATP-binding cassette (ABC) transporter family embedded in the membrane bilayer. P-gp is a polyspecific protein that has demonstrated its function as a transporter of hydrophobic drugs as well as transporting lipids, steroids and metabolic products. Its role in multidrug resistance (MDR) and pharmacokinetic profile of clinically important drug molecules has been widely recognised. In this study, QSAR and enzyme-ligand docking methods were explored in order to classify substrates and non-substrates of P-glycoprotein. A set of 123 compounds designated as substrates (54) or non-substrates (69) by Matsson et al., 2009 was used for the investigation. For QSAR studies, molecular descriptors were calculated using ACD labs/LogD Suite and MOE (CCG Inc.). P-glycoprotein structures available in the Protein data bank were used for docking studies and determination of binding scores using MOE software. Binding sites were defined using co-crystallised ligand structures. Three classification algorithms which included classification and regression trees, boosted trees and support vector machine were examined. Models were developed using a training set of 98 compounds and were validated using the remaining compounds as the external test set. A model generated using BT was identified as the best of three models, with a prediction accuracy of 88%, Mathews correlation coefficient of 0.77 and Youden’s J index of 0.80 for the test set. Inclusion of various docking scores for different binding sites improved the models only marginally

Fixed-Time Convergent Control Barrier Functions for Coupled Multi-Agent Systems Under STL Tasks

This paper presents a control strategy based on a new notion of time-varying fixed-time convergent control barrier functions (TFCBFs) for a class of coupled multi-agent systems under signal temporal logic (STL) tasks. In this framework, each agent is assigned a local STL task regradless of the tasks of other agents. Each task may be dependent on the behavior of other agents which may cause conflicts on the satisfaction of all tasks. Our approach finds a robust solution to guarantee the fixed-time satisfaction of STL tasks in a least violating way and independent of the agents' initial condition in the presence of undesired violation effects of the neighbor agents. Particularly, the robust performance of the task satisfactions can be adjusted in a user-specified way.Comment: Accepted in ECC 202

Correlation of A G to A nucleotide substitution in upstream region of leptin with breast cancer susceptibility

Single nucleotide polymorphisms in leptin gene may increase the risk of breast cancer. The aim of this study was to investigate the association of leptin G-2548A gene polymorphism with breast cancer risk in an Iranian population. In a case-control study, 98 subjects including 45 women with breast cancer and 53 healthy women were recruited. The genotypes of G-2548A polymorphism were detected by polymerase chain reaction-restriction fragment length polymorphism. Our data revealed that there is a significant association between AG homozygote genotype and breast cancer risk (OR= 2.41, 95CI= 1.05-5.52, p= 0.037). Also, we observed that G allele marginally increases the breast cancer risk (OR= 1.92, 95CI= 1.00-3.70, p= 0.049). Based on our preliminary study, leptin G-2548A gene polymorphism may be a genetic risk factor for breast cancer and further studies with larger sample size are required to obtain more accurate results. © 2019, Indian Journal of Forensic Medicine and Toxicology. All rights reserved

Triumph of hope over experience: learning from interventions to reduce avoidable hospital admissions identified through an Academic Health and Social Care Network.

BACKGROUND: Internationally health services are facing increasing demands due to new and more expensive health technologies and treatments, coupled with the needs of an ageing population. Reducing avoidable use of expensive secondary care services, especially high cost admissions where no procedure is carried out, has become a focus for the commissioners of healthcare. METHOD: We set out to identify, evaluate and share learning about interventions to reduce avoidable hospital admission across a regional Academic Health and Social Care Network (AHSN). We conducted a service evaluation identifying initiatives that had taken place across the AHSN. This comprised a literature review, case studies, and two workshops. RESULTS: We identified three types of intervention: pre-hospital; within the emergency department (ED); and post-admission evaluation of appropriateness. Pre-hospital interventions included the use of predictive modelling tools (PARR - Patients at risk of readmission and ACG - Adjusted Clinical Groups) sometimes supported by community matrons or virtual wards. GP-advisers and outreach nurses were employed within the ED. The principal post-hoc interventions were the audit of records in primary care or the application of the Appropriateness Evaluation Protocol (AEP) within the admission ward. Overall there was a shortage of independent evaluation and limited evidence that each intervention had an impact on rates of admission. CONCLUSIONS: Despite the frequency and cost of emergency admission there has been little independent evaluation of interventions to reduce avoidable admission. Commissioners of healthcare should consider interventions at all stages of the admission pathway, including regular audit, to ensure admission thresholds don't change

A Sustainable Water Resources Management Assessment Framework (SWRM-AF) for Arid and Semi-Arid Regions:Part 1: Developing the Conceptual Framework

The evaluation of water resources management practices is essential for water usage decisions in regions with limited water resources. The literature provides numerous assessment frameworks, but many ignore the unique characteristics and conditions of some special arid and semi-arid regions, such as the Gulf Cooperation Council (GCC) countries, which lack any permanent rivers or lakes. Thus, this study, the first in a two-part series, seeks to develop a conceptual Sustainable Water Resources Management Assessment Framework (SWRM-AF). General and particular criteria explain how components and indicators were identified. The conceptual SWRM-AF provided here has four components (environment, economy, society, and infrastructure) and 24 indicators. Almost every indicator has been selected from the literature and is briefly explained and justified. This research presents, possibly for the first time, clear and straightforward directions for evaluating each indicator in colour-coded tables. To create a more holistic framework for arid and semi-arid regions, social indicators like “intervention acceptability” and environmental indicators for assessing the impacts of desalination treatment plants have been added to form a unique framework applicable to such regions. Therefore, the components and indicators of conceptual SWRM-AF could work collectively to aid the process of decision-making. The next phase is validating this framework using a participatory approach

Transition to psychosis: Evaluation of the first-degree relatives of patients with schizophrenia

Objective: Schizophrenia and other psychoses have devastating personal and social impacts and many efforts have been devoted to study prodromal syndromes for psychosis in order to achieve earlier detection and interventions. However, only few studies have been performed in developing countries on this subject, and there is a dearth of evidence in the Iranian population. In this study, we focused on conversion rate to psychosis and changes in prodromal symptoms in a group of first-degree relatives of patients with schizophrenia and to compare the conversion rate in those with and without prodromal symptoms as assessed by the Structured Interview for Prodromal Syndromes (SIPS) and Scale of Prodromal Symptoms (SOPS). Method: Participants were the first-degree relatives of hospitalized patients with schizophrenia at Roozbeh Hospital, Tehran, Iran. At baseline, a trained psychiatrist interviewed the participants using the SIPS and the SOPS and assigned them to high- or low-risk groups either based on the presence of prodromal criteria or seeking mental health services. After 12 months, the same examiner re-evaluated the participants in order to determine the changes in their symptoms and identify the probable transitions to psychosis. Results: One hundred participants, 50 participants within each of high- or low-risk groups, were recruited at baseline. Eight participants dropped out of the study. At the follow-up, the rate of transition to full psychosis among high-risk group was 13 (95 CI 0.029, 0.23), whereas none of the low-risk participants developed psychosis. None of the high-risk participants demonstrated attenuation in their prodromal states after a one-year follow-up. In contrast, of the 50 low-risk participants, three experienced prodromal symptoms for psychosis during this period. High-risk participant's illustrated higher severity in almost all of the SOPS items compared to the low-risk participants at both baseline and follow-up evaluations. Conclusion: Prodromal syndrome for psychosis based on the SIPS and the SOPS was a predictive factor for transition to psychosis after a 12-month period in a group of first-degree relatives of patients with schizophrenia admitted to a psychiatric hospital in Iran. Conducting further studies on this at-risk population is highly recommended in order to provide practical methods for early screening and therapeutic interventions

Enhancing Data-Driven Reachability Analysis using Temporal Logic Side Information

This paper presents algorithms for performing data-driven reachability analysis under temporal logic side information. In certain scenarios, the data-driven reachable sets of a robot can be prohibitively conservative due to the inherent noise in the robot's historical measurement data. In the same scenarios, we often have side information about the robot's expected motion (e.g., limits on how much a robot can move in a one-time step) that could be useful for further specifying the reachability analysis. In this work, we show that if we can model this side information using a signal temporal logic (STL) fragment, we can constrain the data-driven reachability analysis and safely limit the conservatism of the computed reachable sets. Moreover, we provide formal guarantees that, even after incorporating side information, the computed reachable sets still properly over-approximate the robot's future states. Lastly, we empirically validate the practicality of the over-approximation by computing constrained, data-driven reachable sets for the Small-Vehicles-for-Autonomy (SVEA) hardware platform in two driving scenarios.Comment: Accepted at the IEEE International Conference on Robotics and Automation (ICRA 2022

The optical response of Ba_{1-x}K_xBiO_3: Evidence for an unusual coupling mechanism of superconductivity?

We have analysed optical reflectivity data for Ba_{1-x}K_xBiO_3 in the far-infrared region using Migdal-Eliashberg theory and found it inconsistent with standard electron-phonon coupling: Whereas the superconducting state data could be explained using moderate coupling, \lambda=0.7, the normal state properties indicate \lambda \le 0.2. We have found that such behaviour could be understood using a simple model consisting of weak standard electron-phonon coupling plus weak coupling to an unspecified high energy excitation near 0.4 eV. This model is found to be in general agreement with the reflectivity data, except for the predicted superconducting gap size. The additional high energy excitation suggests that the dominant coupling mechanism in Ba_{1-x}K_xBiO_3 is not standard electron-phonon.Comment: 5 pages REVTex, 5 figures, 32 refs, accepted for publication in Phys. Rev.