G\mathcal{G}-SELC: Optimization by sequential elimination of level combinations using genetic algorithms and Gaussian processes

Identifying promising compounds from a vast collection of feasible compounds is an important and yet challenging problem in the pharmaceutical industry. An efficient solution to this problem will help reduce the expenditure at the early stages of drug discovery. In an attempt to solve this problem, Mandal, Wu and Johnson [Technometrics 48 (2006) 273--283] proposed the SELC algorithm. Although powerful, it fails to extract substantial information from the data to guide the search efficiently, as this methodology is not based on any statistical modeling. The proposed approach uses Gaussian Process (GP) modeling to improve upon SELC, and hence named $\mathcal{G}$-SELC. The performance of the proposed methodology is illustrated using four and five dimensional test functions. Finally, we implement the new algorithm on a real pharmaceutical data set for finding a group of chemical compounds with optimal properties.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS199 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Empowering Patients with Central Venous Catheters: Utilizing Evidence-Based Video-Assisted Education to Reduce Central Line-Associated Bloodstream Infections

An evidence-based Central Venous Catheter (CVC) dressing change video was created to enhance patient independence, and to increase resource efficiency among nursing staff in an inpatient pediatric setting in which Central Line-Associated Bloodstream Infection (CLABSI) rates were rising. Pediatric oncology patients confer the highest risk of developing CLABSIs due to long-term CVC access, neutropenic effects of treatment regimens, and constant fluctuations between inpatient, outpatient clinic, and homecare settings. Use of video-assisted education is anticipated to standardize and improve patient care, decrease healthcare costs, and increase nurse productivity, and is widely supported by research. Qualitative data collection was conducted by surveying patients and nursing staff to identify the project’s need, obtain baseline competency levels, and evaluate the effectiveness of the video upon implementation. 71% of nurses identified time as the greatest barrier to education. 94% of nurses selected videos as being a resource that could assist them in providing patient education. 100% of patients stated that the video enhanced their overall understanding of the CVC dressing change process. Significant increases in confidence levels of independently performing CVC dressing changes were shown in over 62% of the patients surveyed. Inpatient nurses are often the first to initiate patient education, and this video provides supplemental resources to facilitate CVC teaching, and overcome some of the primary barriers faced in the inpatient setting during patient education processes

Assessment of drug hypersensitivity with non-irritating concentrations of antibacterial agents for allergic skin tests: a review

Hypersensitivity reactions to antibiotics are common with a prevalence of 6-10% of all adverse reactions. There is a lack of guidelines and standardization of skin tests for the screening of hypersensitivity to all antibiotics, in terms of the methodology, dose and time of evaluation of the tests. Literature from Europe and America suggests the use of non-irritating concentration (NIC) of antibiotics for skin testing such as intra dermal test (IDT), skin prick test (SPT). These are concentrations at which the drug is unlikely to produce irritation by virtue of its chemical nature resulting in false positive reactions. These concentrations have been validated by trials in their populations. Due to the increase of antibiotic resistance in our country, declaring a patient allergic to a specific class of antibiotics based on positive skin tests can further narrow the therapeutic armory. These individuals have an increased incidence of infections with resistant organisms as well as increased cost of hospitalization. This is due to the use of alternative broad spectrum antibiotics. Therefore, there is a need for a standardized protocol for the use of skin tests in screening of hypersensitivity, with validated NIC of all antibacterial agents. The aim of this article is to review literature of protocols for assessment of drug hypersensitivity with NIC of antibacterial drugs for SPT, IDT and also establish the need for research in this area in our country

Possible adverse drug reaction to parenteral amino acids in an infant: a case report

A case report of a possible adverse drug reaction to 10% parenteral aminoacid formulation in a 5½ month male patient diagnosed with bronchopulmonary pneumonia with acute respiratory distress syndrome in septic shock, is presented. There was a temporal relationship between the administration of the parenteral amino acid formulation and the onset of the exanthem. This was further evidenced by the regression of the exanthem following the discontinuation of the formulation. The causality assessment of this adverse drug reaction has been done, and the likely causes of this hypersensitivity reaction have been analyzed

Detection of Maternal and Fetal Stress from the Electrocardiogram with Self-Supervised Representation Learning

In the pregnant mother and her fetus, chronic prenatal stress results in entrainment of the fetal heartbeat by the maternal heartbeat, quantified by the fetal stress index (FSI). Deep learning (DL) is capable of pattern detection in complex medical data with high accuracy in noisy real-life environments, but little is known about DL's utility in non-invasive biometric monitoring during pregnancy. A recently established self-supervised learning (SSL) approach to DL provides emotional recognition from electrocardiogram (ECG). We hypothesized that SSL will identify chronically stressed mother-fetus dyads from the raw maternal abdominal electrocardiograms (aECG), containing fetal and maternal ECG. Chronically stressed mothers and controls matched at enrolment at 32 weeks of gestation were studied. We validated the chronic stress exposure by psychological inventory, maternal hair cortisol and FSI. We tested two variants of SSL architecture, one trained on the generic ECG features for emotional recognition obtained from public datasets and another transfer-learned on a subset of our data. Our DL models accurately detect the chronic stress exposure group (AUROC=0.982+/-0.002), the individual psychological stress score (R2=0.943+/-0.009) and FSI at 34 weeks of gestation (R2=0.946+/-0.013), as well as the maternal hair cortisol at birth reflecting chronic stress exposure (0.931+/-0.006). The best performance was achieved with the DL model trained on the public dataset and using maternal ECG alone. The present DL approach provides a novel source of physiological insights into complex multi-modal relationships between different regulatory systems exposed to chronic stress. The final DL model can be deployed in low-cost regular ECG biosensors as a simple, ubiquitous early stress detection and monitoring tool during pregnancy. This discovery should enable early behavioral interventions.Comment: ClinicalTrials.gov registration number: NCT03389178. Code repo: https://code.engineering.queensu.ca/17ps21/ssl-ecg-v

Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity With Cisplatin

Occurrence of oxidative stress is the principal cause of acute kidney injury induced by cisplatin. Mangiferin, a naturally occurring antioxidant molecule, is found to ameliorate several oxidative stress mediated pathophysiological conditions including cancer. Cisplatin induced cytotoxicity was measured in NKE cells by MTT assay and microscopic analysis. Induction of oxidative stress and regulation of proapoptotic molecules were subsequently investigated by using different spectrophotometric analyses, FACS and immunocytochemistry. Induction of nephrotoxicity was determined by analyzing different serum biomarkers and histological parameters in vivo using swiss albino mice. Activation of NF-κB mediated pro-inflammatory and caspase dependent signaling cascades were investigated by semi-quantitative RT-PCR and immunoblotting. Mangiferin was found to ameliorate cisplatin induced nephrotoxicity in vitro and in vivo by attenuating the induction of oxidative stress and upregulating Nrf-2 mediated pro-survival signaling cascades via the activation of PI3K. Additionally, mangiferin showed synergistic anticancer activity with cisplatin in cancer cell lines (MCF-7 and SKRC-45) and EAC cell induced solid tumor bearing experimental mice. The ameliorative effect of mangiferin is primarily attributed to its anti-oxidant and anti-inflammatory properties. It acts differentially in normal tissue cells and tumor cells by modulating different cell survival regulatory signaling molecules. For the first time, the study reveals a mechanistic basis of mangiferin action against cisplatin induced nephrotoxicity. Since Mangiferin shows synergistic anticancer activity with cisplatin, it can be considered as a promising drug candidate, to be used in combination with cisplatin

Estimation and reconstruction of facial creases based on skull crease morphology

This research explores the relationships between the facial creases and the morphology of the underlying skull for supplementary use during forensic facial reconstruction. The correlation between skull morphology and the patterns of facial creases was obtained using the three-dimensional (3D) skull surface scans from the William Bass skeletal collection at the University of Tennessee, USA, which also provided the related ante-mortem face photographs. Superimposition of the facial crease patterns seen in a face photograph with the related skull image enabled the visual analysis of the correlation between the crease and the skull morphology. Qualitative analysis indicated that the infraorbital crease follows the outline of the orbit in 52% of the subjects, while the nasolabial fold (NLF) relates to the canine fossa in 95% of the subjects. The infraorbital crease and NLF were reconstructed in a blind study using ten 3D surface scan skull models and related face photographs from the Helmer collection available in the Centre for Anatomy and Human Identification, the University of Dundee, UK. Correct prediction was obtained in six specimens (60%). One inconclusive result was due to poor photograph quality and three inaccurate results showed an overestimation of the NLF strength although the location of the crease manifestation was correct

Trade-Offs Between Reducing Complex Terminology and Producing Accurate Interpretations from Environmental DNA: Comment on “Environmental DNA: What\u27s behind the term?” by Pawlowski et al., (2020)

In a recent paper, “Environmental DNA: What\u27s behind the term? Clarifying the terminology and recommendations for its future use in biomonitoring,” Pawlowski et al. argue that the term eDNA should be used to refer to the pool of DNA isolated from environmental samples, as opposed to only extra-organismal DNA from macro-organisms. We agree with this view. However, we are concerned that their proposed two-level terminology specifying sampling environment and targeted taxa is overly simplistic and might hinder rather than improve clear communication about environmental DNA and its use in biomonitoring. This terminology is based on categories that are often difficult to assign and uninformative, and it overlooks a fundamental distinction within eDNA: the type of DNA (organismal or extra-organismal) from which ecological interpretations are derived

Gene-Based Tests of Association

Genome-wide association studies (GWAS) are now used routinely to identify SNPs associated with complex human phenotypes. In several cases, multiple variants within a gene contribute independently to disease risk. Here we introduce a novel Gene-Wide Significance (GWiS) test that uses greedy Bayesian model selection to identify the independent effects within a gene, which are combined to generate a stronger statistical signal. Permutation tests provide p-values that correct for the number of independent tests genome-wide and within each genetic locus. When applied to a dataset comprising 2.5 million SNPs in up to 8,000 individuals measured for various electrocardiography (ECG) parameters, this method identifies more validated associations than conventional GWAS approaches. The method also provides, for the first time, systematic assessments of the number of independent effects within a gene and the fraction of disease-associated genes housing multiple independent effects, observed at 35%–50% of loci in our study. This method can be generalized to other study designs, retains power for low-frequency alleles, and provides gene-based p-values that are directly compatible for pathway-based meta-analysis