Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas.

The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling. These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ. IMDs are integrated into surgical practice during tumor resection and remain in situ only for the duration of the otherwise standard operation (2 to 3 hours). None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens. Analysis of the specimens provided preliminary evidence of the robustness of the readout, compatibility with a wide array of techniques for molecular tissue interrogation, and promising similarities with the available observed clinical-radiological responses to temozolomide. From an investigational aspect, the amount of information obtained with IMDs allows characterization of tissue effects of any drugs of interest, within the physiological context of the intact tumor, and without affecting the standard surgical workflow.

Grand challenges in entomology: Priorities for action in the coming decades.

Entomology is key to understanding terrestrial and freshwater ecosystems at a time of unprecedented anthropogenic environmental change and offers substantial untapped potential to benefit humanity in a variety of ways, from improving agricultural practices to managing vector-borne diseases and inspiring technological advances.We identified high priority challenges for entomology using an inclusive, open, and democratic four-stage prioritisation approach, conducted among the membership and affiliates (hereafter 'members') of the UK-based Royal Entomological Society (RES).A list of 710 challenges was gathered from 189 RES members. Thematic analysis was used to group suggestions, followed by an online vote to determine initial priorities, which were subsequently ranked during an online workshop involving 37 participants.The outcome was a set of 61 priority challenges within four groupings of related themes: (i) 'Fundamental Research' (themes: Taxonomy, 'Blue Skies' [defined as research ideas without immediate practical application], Methods and Techniques); (ii) 'Anthropogenic Impacts and Conservation' (themes: Anthropogenic Impacts, Conservation Options); (iii) 'Uses, Ecosystem Services and Disservices' (themes: Ecosystem Benefits, Technology and Resources [use of insects as a resource, or as inspiration], Pests); (iv) 'Collaboration, Engagement and Training' (themes: Knowledge Access, Training and Collaboration, Societal Engagement).Priority challenges encompass research questions, funding objectives, new technologies, and priorities for outreach and engagement. Examples include training taxonomists, establishing a global network of insect monitoring sites, understanding the extent of insect declines, exploring roles of cultivated insects in food supply chains, and connecting professional with amateur entomologists. Responses to different challenges could be led by amateur and professional entomologists, at all career stages.Overall, the challenges provide a diverse array of options to inspire and initiate entomological activities and reveal the potential of entomology to contribute to addressing global challenges related to human health and well-being, and environmental change.

Functionalized carbon nanotube adsorption interfaces for electron transfer studies of galactose oxidase.

Modified electrodes featuring specific adsorption platforms able to access the electrochemistry of the copper containing enzyme galactose oxidase (GaOx) were explored, including interfaces featuring nanomaterials such as nanoparticles and carbon nanotubes (CNTs). Electrodes modified with various self-assembled monolayers (SAMs) including those with attached nanoparticles or amide-coupled functionalized CNTs were examined for their ability to effectively immobilize GaOx and study the redox activity related to its copper core. While stable GaOx electrochemistry has been notoriously difficult to achieve at modified electrodes, strategically designed functionalized CNT-based interfaces, cysteamine SAM-modified electrode subsequently amide-coupled to carboxylic acid functionalized single wall CNTs, were significantly more effective with high GaOx surface adsorption along with well-defined, more reversible, stable (≥ 8 days) voltammetry and an average ET rate constant of 0.74 s-1 in spite of increased ET distance - a result attributed to effective electronic coupling at the GaOx active site. Both amperometric and fluorescence assay results suggest embedded GaOx remains active. Fundamental ET properties of GaOx may be relevant to biosensor development targeting galactosemia while the use functionalized CNT platforms for adsorption/electrochemistry of electroactive enzymes/proteins may present an approach for fundamental protein electrochemistry and their future use in both direct and indirect biosensor schemes.

A field evaluation of the predictive value of a hand-held drum pressure detection device.

According to Environmental Protection Agency estimates, 20% of hazardous waste drums currently managed in the 6500 known, uncontrolled Superfund removal or remediation sites contain some degree of elevated internal pressurization. This estimate increases to 90% during the summer months, and, overall, up to 5% of the drums stored in active treatment, storage, and disposal facilities may be pressurized. The ability to identify pressurized drums in real-time would enhance worker health and safety, reduce the potential for environmental contamination, and minimize property damage. A prototype hand-held drum pressure detection device was field tested at an active Resource Conservation and Recovery Act mixed waste operation using acoustic resonance spectroscopy technology to identify pressurized drums. The waste operation used a drum venting system that measured the actual drum pressure of retrieved drums. Drum venting system data were analyzed to quantify the ability of the drum pressure detection device to correctly identify drums with elevated internal pressure. After 456 drums were measured, the dichotomous pressure data (pressurized vs. nonpressurized) were analyzed. The relationship between the drum venting system and drum pressure detection device pressure data was found to be statistically significant. With alpha and beta values of 0.05, the negative predictive value was 0.94, the positive predictive value was 0.47, the sensitivity was 0.82, and the specificity was 0.77. Although capable of identifying nonpressurized drums, this instrument may not be appropriate for general use. Study results and critical improvements necessary to improve the instrument's predictive value, specificity, and sensitivity are presented.