Silicon Nanowire Sensors Enable Diagnosis of Patients via Exhaled Breath

Two of the biggest challenges in medicine today are the need to detect diseases in a noninvasive manner and to differentiate between patients using a single diagnostic tool. The current study targets these two challenges by developing a molecularly modified silicon nanowire field effect transistor (SiNW FET) and showing its use in the detection and classification of many disease breathprints (lung cancer, gastric cancer, asthma, and chronic obstructive pulmonary disease). The fabricated SiNW FETs are characterized and optimized based on a training set that correlate their sensitivity and selectivity toward volatile organic compounds (VOCs) linked with the various disease breathprints. The best sensors obtained in the training set are then examined under real-world clinical conditions, using breath samples from 374 subjects. Analysis of the clinical samples show that the optimized SiNW FETs can detect and discriminate between almost all binary comparisons of the diseases under examination with >80% accuracy. Overall, this approach has the potential to support detection of many diseases in a direct harmless way, which can reassure patients and prevent numerous unpleasant investigations

Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma.

Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Aktuelle Praxis und Perspektiven beim CRO-Oversight für Biostatistik- & Data Management-Dienstleistungen - Umfrage unter den Mitgliedern des Verbandes Forschender Arzneimittelhersteller (vfa)

Outsourcing of activities is common and increasing in the pharmaceutical industry, not only for clinical trial conduct, or other trial related aspects but also for biostatistics and data management. This raises the question of whether and how sponsors retain the capability to select and to control the CRO(s) involved and what biometrical expertise still has to be present in the sponsor company to ensure adequate oversight. Not only in the case of partial outsourcing but especially in the case of complete outsourcing sponsors have to find the right balance between a complete "hands off" approach and a resource intensive in-house shadowing of activities to fulfil the requirements.In order to answer these questions, a survey was conducted among the German vfa member companies. This article discusses the specific oversight topics for the outsourcing of data management and biostatistics services, e.g. requirements for data quality, coding, and statistical analyses.This study shows that the majority of the companies use the same CRO for biometrical services as for rest of study services and that there is a preferred provider for these services in 65% of the companies. There are established, specific requirements for the main deliverables of biometrical services: For coding and data standards these are predominantly industry standards (MedDRA, CDISC). For statistic outputs and data quality mainly sponsor standards are used. The adherence to the requirements is mainly checked via spot-checks, and standardized checklists are mainly used for checking data standards. Generally, in all companies participating in the survey, there is an awareness of the necessity of biometrical oversight. Although not necessarily perfect yet, all companies took measures to ensure good biometrical oversight and there is a common understanding, that it is not an option to resign from biometrical oversight.Auslagerung ("Outsourcing ") von Aktivitäten ist üblich und nimmt in der pharmazeutischen Industrie weiter zu - dies trifft nicht nur für die Durchführung von klinischen Studien, sondern insbesondere auch für Biostatistik- und Datenmanagement-Dienstleistungen zu.Dies wirft die Frage auf, ob und wie Sponsoren die Möglichkeit behalten, CROs adäquat auszuwählen und zu kontrollieren und welche biometrische Expertise noch beim Sponsor vorhanden sein muss, um eine angemessene "Oversight " sicher zu stellen. Nicht nur im Falle der partiellen Auslagerung, sondern vor allem im Falle der kompletten Auslagerung müssen Sponsoren die richtige Balance zwischen einem kompletten unkontrollierten Überlassen aller Aktivitäten und einer Ressource-intensiven Wiederholung aller Aktivitäten finden, um ihrer Sponsoren-Verpflichtung gerecht zu werden.Um diese Fragen zu beantworten, wurde eine Umfrage unter den deutschen vfa-Mitgliedsunternehmen durchgeführt. Dieser Artikel beschreibt die spezifischen Oversight -Themen für die Auslagerung von Diensten aus den Bereichen Data Management und Biostatistik; es geht somit um Anforderungen hinsichtlich Datenqualität, Codierung und statistischer Analysen. Diese Studie zeigt, dass die Mehrheit der Unternehmen die gleichen CROs für biometrische Dienstleistungen wie für andere Dienstleistungen verwenden und dass es einen bevorzugten Anbieter ("preferred provider" ) für biometrische Dienstleistungen in 65% der Unternehmen gibt. Es gibt etablierte, spezifische Anforderungen für die Ergebnisse der biometrischen Dienstleistungen hinsichtlich Codierung und Daten-Standards (Industriestandards wie MedDRA und CDISC). Für die Darstellung der Ergebnisse von statistischen Analysen und für die Datenqualität werden vor allem Standards der Sponsoren verwendet. Die Einhaltung der Anforderungen wird vor allem auf Stichproben-Basis überprüft, während standardisierte Checklisten vorwiegend bei der Überprüfung von Datenstandards Anwendung finden. Grundsätzlich gibt es in allen Unternehmen, die an der Umfrage teilgenommen haben, ein Bewusstsein für die Notwendigkeit der biometrischen Aufsicht. Obwohl noch nicht überall unbedingt perfekt implementiert, ergreifen alle Unternehmen Maßnahmen, um eine gute biometrische Kontrolle zu gewährleisten. Es gibt ein gemeinsames Verständnis dafür, dass es keine Alternative zum effektiven biometrischen Oversight gibt

Ridge Resonance in Silicon Photonics Harnessing Bound States in the Continuum

The theoretical analysis and experimental demonstration of a waveguide resonator are presented based on bound states in the continuum in an integrated photonic chip platform. The continuum has the form of a collimated beam of light which is confined vertically in a transverse electric (TE) mode of a silicon slab. The bound state is a discrete transverse-magnetic (TM)-like mode of a ridge on the silicon slab. The coupling between the slab and ridge modes results in a single sharp resonance at the wavelength where they phase match. This phenomenon is experimentally demonstrated on a silicon photonic chip using foundry-compatible parameters and it is interfaced on-chip to standard single-mode silicon nanowire waveguides. The fabricated chip exhibits a single sharp resonance near 1550 nm with a line width of a few nanometers, an extinction ratio of 25 dB, and a thermal stability of 19.5 pm °C−1. It is believed that the demonstration of a resonance operating near a bound state in the continuum realized using guided wave components will form the basis of a new approach to on-chip wavelength filtering and sensing applications

Dynamic drag force based on iterative density mapping: A new numerical tool for three-dimensional analysis of particle trajectories in a dielectrophoretic system

Dielectrophoresis is a widely used means of manipulating suspended particles within microfluidic systems. In order to efficiently design such systems for a desired application, various numerical methods exist that enable particle trajectory plotting in two or three dimensions based on the interplay of hydrodynamic and dielectrophoretic forces. While various models are described in the literature, few are capable of modeling interactions between particles as well as their surrounding environment as these interactions are complex, multifaceted, and computationally expensive to the point of being prohibitive when considering a large number of particles. In this paper, we present a numerical model designed to enable spatial analysis of the physical effects exerted upon particles within microfluidic systems employing dielectrophoresis. The model presents a means of approximating the effects of the presence of large numbers of particles through dynamically adjusting hydrodynamic drag force based on particle density, thereby introducing a measure of emulated particle-particle and particle-liquid interactions. This model is referred to as "dynamic drag force based on iterative density mapping." The resultant numerical model is used to simulate and predict particle trajectory and velocity profiles within a microfluidic system incorporating curved dielectrophoretic microelectrodes. The simulated data are compared favorably with experimental data gathered using microparticle image velocimetry, and is contrasted against simulated data generated using traditional "effective moment Stokes-drag method," showing more accurate particle velocity profiles for areas of high particle density