Asymptomatic Intracorneal Graphite Deposits following Graphite Pencil Injury

Reports of graphite pencil lead injuries to the eye are rare. Although graphite is considered to remain inert in the eye, it has been known to cause severe inflammation and damage to ocular structures. We report a case of a 12-year-old girl with intracorneal graphite foreign bodies following a graphite pencil injury

Evaluation of two repellent semiochemicals for disruption of attack by the mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Scolytidae)

When released from attractant-baited multiple-funnel traps, 3-methyl-2-cyclohexen-1- one (MCH) reduced catches of male and female mountain pine beetles, Dendroctonus ponderosae Hopkins, by 67.4% and 71.8%, respectively. 2-Phenyl ethanol reduced the respective catches by 96.6% and 95.1%, but only verbenone and all three compounds together reduced catches to levels no different from those in unbaited control traps. In another experiment, all three binary combinations of the above compounds, plus the ternary combination, reduced catches of both sexes by >96%. In comparable tree protection experiments near Princeton BC, MCH and 2-phenyl ethanol alone and together significantly reduced the percentages of pheromone-baited lodgepole pines that were attacked by 16.0%, 33.3% and 40.0%, respectively, but verbenone alone totally protected baited trees, and many trees within 5 m of them, from attack. In identical experiments near Prince George BC, where mountain pine beetle populations were much higher, adding MCH, 2-phenyl ethanol or both together to verbenone did not cause attack to be reduced significantly beyond that achieved by verbenone alone. Our results confirm that 2-phenyl ethanol is an antiaggregation pheromone for the mountain pine beetle, and that MCH is an interspecific synomone. However, because neither was as effective as verbenone in protecting pheromone-baited trees from attack, and adding either or both to verbenone did not improve protection, neither compound warrants further consideration as a potential tool for operational disruption of attack

WaveCNV: allele-specific copy number alterations in primary tumors and xenograft models from next-generation sequencing.

MotivationCopy number variations (CNVs) are a major source of genomic variability and are especially significant in cancer. Until recently microarray technologies have been used to characterize CNVs in genomes. However, advances in next-generation sequencing technology offer significant opportunities to deduce copy number directly from genome sequencing data. Unfortunately cancer genomes differ from normal genomes in several aspects that make them far less amenable to copy number detection. For example, cancer genomes are often aneuploid and an admixture of diploid/non-tumor cell fractions. Also patient-derived xenograft models can be laden with mouse contamination that strongly affects accurate assignment of copy number. Hence, there is a need to develop analytical tools that can take into account cancer-specific parameters for detecting CNVs directly from genome sequencing data.ResultsWe have developed WaveCNV, a software package to identify copy number alterations by detecting breakpoints of CNVs using translation-invariant discrete wavelet transforms and assign digitized copy numbers to each event using next-generation sequencing data. We also assign alleles specifying the chromosomal ratio following duplication/loss. We verified copy number calls using both microarray (correlation coefficient 0.97) and quantitative polymerase chain reaction (correlation coefficient 0.94) and found them to be highly concordant. We demonstrate its utility in pancreatic primary and xenograft sequencing data.Availability and implementationSource code and executables are available at https://github.com/WaveCNV. The segmentation algorithm is implemented in MATLAB, and copy number assignment is implemented [email protected] informationSupplementary data are available at Bioinformatics online

Patient perceptions about virtual clinical consultations during current COVID-19 pandemic: A multi-city survey across India

Introduction: COVID-19 has prevented many patients from accessing health care through traditional face-to-face clinic visits. Consequently, online consultations have gained popularity. Aim: To explore patient perceptions regarding virtual consultations. Methods: A voluntary online survey using a mix of quantitative and qualitative questions was administered to patients across selected cities in India using a social media platform. Responses were used to explore the characteristics of users, perceived advantages and disadvantages of online consultations and patient satisfaction. Results: There were 679 respondents (M 52.4%: F 47.6%) that had consulted doctors online; 91.8% were from 8 major metro cities. Interestingly, over 80% had never sought online consultation before the COVID-19 pandemic. 46% consultations were via videocalls, 26% through WhatsApp and 21% via telephone calls. The main advantages of online consultations cited by patients included a lower risk of infection (78.8%), reduced waiting time (56.8%) and travel time (58.3%). The main disadvantages included a lack of physical examination (73.4%), a perception that this was not as satisfying as a face-to face consultation (37.9%) and difficulty in communication (24.5%). 78.6% patients rated their online consultations as either good or very good. However, given the choice, almost two-thirds felt they would still prefer face-face consultations. Conclusion: High levels of satisfaction from this survey suggests that teleconsultation has the potential to become a complementary method to access clinical care even after restrictions from the pandemic cease. The disadvantages of online consultations could be mitigated through evolving technologies such as digital stethoscopes and improvement in communication tools

Vector Field Driven Design for Lightweight Signal Processing and Control Schemes for Autonomous Robotic Navigation

We address the problem of realizing lightweight signal processing and control architectures for agents in multirobot systems. Motivated by the promising results of neuromorphic engineering which suggest the efficacy of analog as an implementation substrate for computation, we present the design of an analog-amenable signal processing scheme. We use control and dynamical systems theory both as a description language and as a synthesis toolset to rigorously develop our computational machinery; these mechanisms are mated with structural insights from behavior-based robotics to compose overall algorithmic architectures. Our perspective is that robotic behaviors consist of actions taken by an agent to cause its sensory perception of the environment to evolve in a desired manner. To provide an intuitive aid for designing these behavioral primitives we present a novel visual tool, inspired vector field design, that helps the designer to exploit the dynamics of the environment. We present simulation results and animation videos to demonstrate the signal processing and control architecture in action

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.

Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets

Following Natures Lead: On the Construction of Membrane-Inserted Toxins in Lipid Bilayer Nanodiscs

Bacterial toxin or viral entry into the cell often requires cell surface binding and endocytosis. The endosomal acidification induces a limited unfolding/refolding and membrane insertion reaction of the soluble toxins or viral proteins into their translocation competent or membrane inserted states. At the molecular level, the specific orientation and immobilization of the pre-transitioned toxin on the cell surface is often an important prerequisite prior to cell entry. We propose that structures of some toxin membrane insertion complexes may be observed through procedures where one rationally immobilizes the soluble toxin so that potential unfolding ↔ refolding transitions that occur prior to membrane insertion orientate away from the immobilization surface in the presence of lipid micelle pre-nanodisc structures. As a specific example, the immobilized prepore form of the anthrax toxin pore translocon or protective antigen can be transitioned, inserted into a model lipid membrane (nanodiscs), and released from the immobilized support in its membrane solubilized form. This particular strategy, although unconventional, is a useful procedure for generating pure membrane-inserted toxins in nanodiscs for electron microscopy structural analysis. In addition, generating a similar immobilized platform on label-free biosensor surfaces allows one to observe the kinetics of these acid-induced membrane insertion transitions. These platforms can facilitate the rational design of inhibitors that specifically target the toxin membrane insertion transitions that occur during endosomal acidification. This approach may lead to a new class of direct anti-toxin inhibitors