1877-08-09

The Old Commonwealth was a weekly newspaper published in Harrisonburg, Va., between 1865 and 1884

A new social gene in Dictyostelium discoideum, chtB

Background: Competitive social interactions are ubiquitous in nature, but their genetic basis is difficult to determine. Much can be learned from single gene knockouts in a eukaryote microbe. The mutants can be competed with the parent to discern the social impact of that specific gene. Dictyostelium discoideum is a social amoeba that exhibits cooperative behavior in the construction of a multicellular fruiting body. It is a good model organism to study the genetic basis of cooperation since it has a sequenced genome and it is amenable to genetic manipulation. When two strains of D. discoideum are mixed, a cheater strain can exploit its social partner by differentiating more spore than its fair share relative to stalk cells. Cheater strains can be generated in the lab or found in the wild and genetic analyses have shown that cheating behavior can be achieved through many pathways. Results: We have characterized the knockout mutant chtB, which was isolated from a screen for cheater mutants that were also able to form normal fruiting bodies on their own. When mixed in equal proportions with parental strain cells, chtB mutants contributed almost 60% of the total number of spores. To do so, chtB cells inhibit wild type cells from becoming spores, as indicated by counts and by the wild type cells’ reduced expression of the prespore gene, cotB. We found no obvious fitness costs (morphology, doubling time in liquid medium, spore production, and germination efficiency) associated with the cheating ability of the chtB knockout. Conclusions: In this study we describe a new gene in D. discoideum, chtB, which when knocked out inhibits the parental strain from producing spores. Moreover, under lab conditions, we did not detect any fitness costs associated with this behavior

A wearable microwave antenna array for time-domain breast tumor screening

In this work, we present a clinical prototype with a wearable patient interface for microwave breast cancer detection. The long-term aim of the prototype is a breast health monitoring application. The system operates using multistatic time-domain pulsed radar, with 16 flexible antennas embedded into a bra. Unlike the previously reported, table-based prototype with a rigid cup-like holder, the wearable one requires no immersion medium and enables simple localization of breast surface. In comparison with the table-based prototype, the wearable one is also significantly more cost-effective and has a smaller footprint. To demonstrate the improved functionality of the wearable prototype, we here report the outcome of daily testing of the new, wearable prototype on a healthy volunteer over a 28-day period. The resulting data (both signals and reconstructed images) is compared to that obtained with our table-based prototype. We show that the use of the wearable prototype has improved the quality of collected volunteer data by every investigated measure. This work demonstrates the proof-of-concept for a wearable breast health monitoring array, which can be further optimized in the future for use with patients with various breast sizes and tissue densities

The Perceptions of People with Dementia and Key Stakeholders Regarding the Use and Impact of the Social Robot MARIO

People with dementia often experience loneliness and social isolation. This can result in increased cognitive decline which, in turn, has a negative impact on quality of life. This paper explores the use of the social robot, MARIO, with older people living with dementia as a way of addressing these issues. A descriptive qualitative study was conducted to explore the perceptions and experiences of the use and impact of MARIO. The research took place in the UK, Italy and Ireland. Semi-structured interviews were held in each location with people with dementia (n = 38), relatives/carers (n = 28), formal carers (n = 28) and managers (n = 13). The data was analyzed using qualitative content analysis. The findings revealed that despite challenges in relation to voice recognition and the practicalities of conducting research involving robots in real-life settings, most participants were positive about MARIO. Through the robot’s user-led design and personalized applications, MARIO provided a point of interest, social activities, and cognitive engagement increased. However, some formal carers and managers voiced concern that robots might replace care staff

Design and Performance of the XENON10 Dark Matter Experiment

XENON10 is the first two-phase xenon time projection chamber (TPC) developed within the XENON dark matter search program. The TPC, with an active liquid xenon (LXe) mass of about 14 kg, was installed at the Gran Sasso underground laboratory (LNGS) in Italy, and operated for more than one year, with excellent stability and performance. Results from a dark matter search with XENON10 have been published elsewhere. In this paper, we summarize the design and performance of the detector and its subsystems, based on calibration data using sources of gamma-rays and neutrons as well as background and Monte Carlo simulations data. The results on the detector's energy threshold, energy and position resolution, and overall efficiency show a performance that exceeds design specifications, in view of the very low energy threshold achieved (<10 keVr) and the excellent energy resolution achieved by combining the ionization and scintillation signals, detected simultaneously

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A compact and low-cost microwave radar prototype for breast health monitoring

Early detection of breast cancer is imperative to ensure successful treatment of the disease, motivating researchers to develop medical devices that can allow for an easily-accessible screening protocol. Currently, X-ray mammography is regarded as the "gold-standard" for screening technologies. However, it suffers from several drawbacks: i) it exposes patients to ionizing radiation, ii) the exam requires the painful compression of the breast, iii) it has difficulty imaging the breasts of young women, and iv) the high associated cost of an X-ray machine and dedicated radiologist and technician. Microwave systems operate based on the intrinsic differences in dielectric properties between healthy and malignant tissues. These systems can exploit recent advances in wireless and telecommunication technologies to develop a low-cost, compression-free, non-ionizing medical device. Such a device can allow for the implementation of a breast cancer screening protocol worldwide and for more frequent scans starting at a younger age. This thesis is focused on hardware and software developments and the design of a low-cost flexible prototype for early-stage breast cancer detection. The advances proposed in this thesis are focused towards the long-term research goal of developing a medical device that will allow for the monitoring of breast health with regular scans to enable the detection of abnormalities at an early stage.First, this thesis presents an overview of the development of a clinically tested experimental system. The system is built from generic off-the-shelf components as a first prototype. A discussion of the various components and their associated cost is included. Successful images of realistic breast phantoms are generated and the system is tested with 13 healthy volunteers over several months. With this system, various signal processing methods are tested on the realistic breast phantoms to help mitigate noise (calibration and artifact removal techniques) and to detect the presence of a tumour (machine learning classification techniques).Various tissue mimicking materials are fabricated from a mixture of polyurethane, graphite, carbon black, and acetone that can represent tissues over a wide range of dielectric properties. A variety of different hemi-spherical breast phantoms, with skin, fat, gland, and tumour structures are then fabricated from these tissue mimicking materials. The development of these stable phantoms allows for the testing of various hardware systems on the same phantoms. The quality of these phantoms are verified through imaging techniques and classification algorithms with the initial experimental system and finally with X-ray and magnetic resonance imaging (MRI). The design and testing of a flexible multi-layer circuit board for use in a custom-built microwave system for breast health monitoring is then presented. The flexible circuit features both an integrated solid-state switching network and 16 wideband antennas. The integration of the switching matrix and the antenna array on the same substrate represents the first time that these hardware components have been integrated into a single structure. The circuit board is integrated into a previously developed clinically tested system and successful images of realistic breast phantoms are presented. The thesis is then focused on addressing the miniaturization and development of custom-built hardware components to replace the remaining off-the-shelf components within the system. Pulse generation and data acquisition are the core concepts that are addressed, as several possible solutions are explored. Lastly, the investigation of an early clinical trial conducted in a hospital, along with good clinical practice and the associated challenges, are described. This work represents a step towards a more patient-friendly, compact, cost-effective medical prototype for breast health monitoring.La détection précoce du cancer du sein est impérative pour assurer un traitement efficace de la maladie, ce qui motive les chercheurs à développer des nouveau system médicaux qui peuvent permettre un protocole de dépistage facilement accessible. Présentement, mammographie par rayons X est la plus utilisée systèmes pour le dépistage du cancer du sein. Par contre, il y a plusieurs négatifs associés avec mammographie : i) il expose les patient aux radiations ionisants, ii) l'examen nécessite la compression douloureuse du sein, iii) il a des difficultés d'imagerie des seins de jeunes femmes, et iv) le coût élevé associé d'une machine à rayons X et radiologue et technicien dédié.Les systèmes hyperfréquences fonctionnent basée sur les différences intrinsèques dans les propriétés diélectriques entre les tissus sains et malins. Ces systèmes peuvent exploiter les progrès récents dans les technologies sans fil pour développer un dispositif médical non ionisant à faible coût. Un tel dispositif peut permettre d'un protocole de dépistage du cancer du sein dans le monde entier et pour des examens plus fréquents à partir d'un âge plus jeune.Les progrès proposés dans cette thèse sont axés sur l'objectif à long terme de la recherche de développer un dispositif médical qui permettra de surveiller la santé du sein avec des examens réguliers pour permettre la détection des anomalies à un stade précoce.Premièrement, cette thèse présente un aperçu du développement d'un système expérimental qui était testé cliniquement. Le système est construit des éléments génériques comme premier prototype. Une discussion sur les différents éléments et leur coût associé est incluse. Le système était testé avec des fantômes mammaires et aussi avec 13 volontaires sains. Avec ce système, différentes méthodes de traitement du signal sont testées pour atténuer le bruit (étalonnage et techniques d'élimination des artefacts) et pour détecter la présence d'une tumeur (techniques de classification par apprentissage automatique).Divers matériaux qui peut imiter des tissus sont fabriqués à partir d'un mélange de polyuréthane, de graphite, de noir de carbone et d'acétone. Ces matériels peuvent représenter des divers tissus sur une large gamme de propriétés diélectriques. Une variété de fantômes de sein hémi-sphériques avec des structures de peau, de graisse, de glande, et de tumeur sont ensuite fabriqués à partir de ces matériaux imitant des tissus. Le développement de ces fantômes stables permet de tester différents systèmes sur les mêmes fantômes. La qualité de ces fantômes est vérifiée par des techniques d'imagerie et des algorithmes de classification avec le système expérimental initial et enfin avec l'imagerie par résonance magnétique (IRM) et rayons X.La conception et l'analyse d'un circuit imprimé multicouches et flexible, pour utilisation dans un système de micro-ondes, pour la surveillance de la santé du sein est ensuite présenté. Le circuit flexible comporte à la fois un réseau de commutation à semi-conducteurs intégré et 16 antennes à large bande. L'intégration de la réseau de commutation et du réseau d'antennes sur le même substrat représente la première fois que ces éléments ont été intégrés dans une structure unique. Le circuit imprimé est intégrée dans un système testé cliniquement et développé avec succès des images de fantômes de sein réalistes. La thèse est ensuite axée sur la miniaturisation et le développement de composants matériels pour remplacer les éléments restants dans le système. La génération de signaux et l'acquisition de données sont les concepts fondamentaux qui sont analysées. Enfin, l'étude d'un essai clinique précoce menée dans un hôpital, ainsi que les bonnes pratiques cliniques et les défis associés, sont décrits. Ce travail représente une étape vers un prototype médical plus convivial, plus compact et à coût faible pour la surveillance de la santé des seins

Breast screening with custom-shaped pulsed microwaves

Microwave imaging has been proposed as a possible complimentary imaging technique to X-ray mammography for early-stage breast cancer detection and screening. Based on the intrinsic differences in the various tissues of the breast at microwave frequencies, microwave imaging offers an imaging modality that is safe, pain-free, and without limitations on the frequency of the exam.An initial time domain microwave imaging system has been previously developed within our group. Accurate numerical models, for finite-difference time-domain simulations, matched to the experimental system have been developed. Numerical simulations are used to assess the safety of the microwave imaging technique. We calculate the maximum energy absorbed by the breast when exposed to incident microwaves and ensure that these values fall within the established thresholds.In this thesis we will test our hypothesis that an augmented microwave imaging system can improve tumour detection by making use of custom-made pulses with critical frequency content. We integrate passive microwave circuitry with a previously designed experimental microwave imaging system in order to create a new system that transmits an optimized pulse. We contrast measurement results of this newly developed system with those of the previously developed experimental system when imaging various tissue phantoms.L'imagerie micro-ondes a été proposée comme une nouvelle technique pour la détection du cancer du sein qui est complémentaire au mammographie. Cette technique est basée sur les differences intrinsèques des tissus mammaires différents à des frequences micro-ondes. L'imagerie mirco-onde est une technique qui est sûr, sans douleur, et sans limitations sur la fréquence de l'examen.Un système préliminaire pour l'imagerie micro-ondes dans le domaine temporel a déjà été mis au point. Des modèles numériques précis , pour les simulations avec la "finite-difference time-domain" technique, qui sont en accorde avec la système expérimental sont construit.Des simulations sont utilisé pour évaluer la sécurité de la technique d'imagerie micro-ondes. Nous calculons le maximum d'énergie absorbée par le sein quand il est exposé aux micro-ondes incidentes et nous s'assure que les résultats sont en accord avec les normes établis. Dans cette thèse, nous allons tester notre hypothèse que un système d'imagerie micro-ondes augmentée peut améliorer la détection des cancers en utilisant des impulsions fait sur-mesure. Nous utilisons des circuits micro-ondes passives, avec le système déjà développé, pour créer un nouveau système qui transmet un impulsion optimisé. On compare les résultats de nos mesures avec les deux systèmes quand on utilise des fantômes de tissus divers

Brain haemorrhage detection using a SVM classifier with electrical impedance tomography measurement frames

Brain haemorrhages often require urgent treatment with a consequent need for quick and accurate diagnosis. Therefore, in this study, we investigate Support Vector Machine (SVM) classifiers for detecting brain haemorrhages using Electrical Impedance Tomography (EIT) measurement frames. A 2-layer model of the head, along with a series of haemorrhages, is designed as both numerical models and physical phantoms. EIT measurement frames, taken from an electrode array placed on the head surface, are used to train and test linear SVM classifiers. Various scenarios are implemented on both platforms to examine the impact of variables such as noise level, lesion location, lesion size, variation in electrode positioning, and variation in anatomy, on the classifier performance. The classifier performed well in numerical models (sensitivity and specificity of 90%(+)) with signal-to-noise ratios of 60 dB(+), was independent of lesion location, and could detect lesions reliably down to the tested minimum volume of 5 ml. Slight variations in electrode layout did not affect performance. Performance was affected by variations in anatomy however, emphasising the need for large training sets covering different anatomies. The phantom models proved more challenging, with maximal sensitivity and specificity of 75% when used with the linear SVM. Finally, the performance of two more complex classifiers is briefly examined and compared to the linear SVM classifier. These results demonstrate that a radial basis function (RBF) SVM classifier and a neural network classifier can improve detection accuracy. Classifiers applied to EIT measurement frames is a novel approach for lesion detection and may offer an effective diagnostic tool clinically. A challenge is to translate the strong results from numerical models into real world phantoms and ultimately human patients, as well as the selection and development of optimal classifiers for this application.peer-reviewe