Using a quantum dot as a high-frequency shot noise detector

We present the experimental realization of a Quantum Dot (QD) operating as a high-frequency noise detector. Current fluctuations produced in a nearby Quantum Point Contact (QPC) ionize the QD and induce transport through excited states. The resulting transient current through the QD represents our detector signal. We investigate its dependence on the QPC transmission and voltage bias. We observe and explain a quantum threshold feature and a saturation in the detector signal. This experimental and theoretical study is relevant in understanding the backaction of a QPC used as a charge detector.Comment: 4 pages, 4 figures, accepted for publication in Physical Review Letter

p-mTOR, p-ERK and PTEN Expression in Tumor Biopsies and Organoids as Predictive Biomarkers for Patients with HPV Negative Head and Neck Cancer

Background: Survival rates of head and neck squamous cell carcinoma (HNSCC) have only marginally improved in the last decades. Hence there is a need for predictive biomarkers for long-time survival that can help to guide treatment decisions and might lead to the development of new therapies. The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway is the most frequently altered pathway in HNSCC, genes are often mutated, amplificated and overexpressed causing aberrant signaling affecting cell growth and differentiation. Numerous genetic alterations of upstream and downstream factors have currently been clarified. However, their predictive value has yet to be established. Therefore we assess the predictive value of p-mTOR, p-ERK and PTEN expression. Methods: Tissue microarrays (TMA’s) of HPV-negative patients with oropharyngeal (n = 48), hypopharyngeal (n = 16) or laryngeal (n = 13) SCC, treated with primary chemoradiation (cisplatin/carboplatin/cetuximab and radiotherapy), were histologically stained for p-mTOR, PTEN and p-ERK. Expression was correlated to overall survival (OS), disease free survival (DFS) and locoregional control (LRC). Also p-mTOR was histologically stained in a separate cohort of HNSCC organoids (n = 8) and correlated to mTOR-inhibitor everolimus response. Results: High p-mTOR expression correlated significantly with worse OS in multivariate analysis in the whole patient cohort [Hazar Ratio (HR) 1.06, 95%CI 1.01–1.11, p = 0.03] and in the cisplatin/carboplatin group with both worse OS (HR 1.09, 95%CI 1.02–1.16, p = 0.02) and DFS (HR 1.06, 95%CI 1.00–1.12, p = 0,04). p-ERK expression correlated significantly with DFS in univariate analysis in the whole patient cohort (HR 1.03, 95%CI 1.00–1.05, p = 0.04) and cisplatin/carboplatin group (HR 1.03, 95%CI 1.00–1.07, p = 0.04). PTEN-expression did not correlate with OS/DFS/LRC. Better organoid response to everolimus correlated significantly to higher p-mTOR expression (Rs = − 0.731, p = 0.04). Conclusions: High p-mTOR expression predicts and high p-ERK expression tends to predict worse treatment outcome in HPV negative HNSCC patients treated with chemoradiation, providing additional evidence that these markers are candidate prognostic biomarkers for survival in this patient population. Also this study shows that the use of HNSCC organoids for biomarker research has potential. The role of PTEN expression as prognostic biomarker remains unclear, as consistent evidence on its prognostic and predictive value is lacking.</p

Current Accuracy of Augmented Reality Neuronavigation Systems: Systematic Review and Meta-Analysis

BACKGROUND Augmented reality neuronavigation (ARN) systems can overlay three-dimensional anatomy and pathology without the need for a two-dimensional external monitor. Accuracy is crucial for their clinical applicability. We performed a systematic review regarding the reported accuracy of ARN systems and compared them with the accuracy of conventional infrared neuronavigation (CIN). OBJECTIVE Explore the current navigation accuracy of ARN systems and compare them with CIN. METHODS Pubmed and Embase were searched for ARN and CIN systems. For ARN: type of system, method of patient-to-image registration, accuracy method and accuracy of the system was noted. For CIN: navigation accuracy, expressed as target registration error (TRE), was noted. A meta-analysis was performed comparing the TRE of ARN and CIN systems. RESULTS 35 studies were included, 12 for ARN and 23 for CIN. ARN systems were divided into head-mounted display and heads-up display. In ARN, four methods were encountered for patient-to-image registration, of which point-pair matching was the one most frequently used. Five methods for assessing accuracy were described. 94 TRE measurements of ARN systems were compared with 9058 TRE measurements of CIN systems. Mean TRE was 2.5 mm (CI 95% 0.7 - 4.4) for ARN systems and 2.6 mm (CI 95% 2.1 - 3.1) for CIN systems. CONCLUSIONS In ARN, there seems to be lack of agreement regarding the best method to assess accuracy. Nevertheless, ARN systems seem able to achieve an accuracy comparable with CIN systems. Future studies should be prospective and compare TREs which should be measured in a standardized fashion

An improved constraint satisfaction adaptive neural network for job-shop scheduling

Copyright @ Springer Science + Business Media, LLC 2009This paper presents an improved constraint satisfaction adaptive neural network for job-shop scheduling problems. The neural network is constructed based on the constraint conditions of a job-shop scheduling problem. Its structure and neuron connections can change adaptively according to the real-time constraint satisfaction situations that arise during the solving process. Several heuristics are also integrated within the neural network to enhance its convergence, accelerate its convergence, and improve the quality of the solutions produced. An experimental study based on a set of benchmark job-shop scheduling problems shows that the improved constraint satisfaction adaptive neural network outperforms the original constraint satisfaction adaptive neural network in terms of computational time and the quality of schedules it produces. The neural network approach is also experimentally validated to outperform three classical heuristic algorithms that are widely used as the basis of many state-of-the-art scheduling systems. Hence, it may also be used to construct advanced job-shop scheduling systems.This work was supported in part by the Engineering and Physical Sciences Research Council (EPSRC) of UK under Grant EP/E060722/01 and in part by the National Nature Science Fundation of China under Grant 60821063 and National Basic Research Program of China under Grant 2009CB320601

Improving primary care antimicrobial stewardship by implementing a peer audit and feedback intervention in Cape Town community healthcare centres

Background. The increasing prevalence of antibiotic resistance is a major threat to public health. Primary care, where 80% of antibiotics are consumed, is a pivotal setting to direct antimicrobial stewardship (AMS) efforts. However, the ideal model to improve antibiotic prescribing in primary care in low-resource settings is not known.Objective. To implement a multidisciplinary audit and feedback AMS intervention with the aim to improve appropriate antibiotic prescribing at primary care level.Methods. The intervention was implemented and monitored in 10 primary care centres of the Cape Town metropole between July 2017 and June 2019. The primary and secondary outcome measures were monthly adherence to a bundle of antibiotic quality process measures and monthly antibiotic consumption, respectively. Multidisciplinary audit and feedback meetings were initiated and integrated into facility clinical meetings. Two Excel tools were utilised to automatically calculate facility audit scores and consumption. Once a month, 10 antibiotic prescriptions were randomly selected for a peer review audit by the team. The prescriptions were audited for adherence to a bundle of seven antibiotic process measures using the standard treatment guidelines (STG) and Essential Medicines List (EML) as standard. Concurrently, primary care pharmacists monitored monthly antibiotic consumption by calculating defined daily doses (DDDs) per 100 prescriptions dispensed. Adherence and consumption feedback were regularly provided to the facilities. Learning collaboratives involving representative multidisciplinary teams were held twice-yearly. Pre-, baseline and post-intervention periods were defined as 6 months before, first 6 months and last 6 months of the study, respectively.Results. The mean overall adherence increased from 19% (baseline) to 47% (post intervention) (p&lt;0.001). Of the 2 077 prescriptions analysed, 33.7% had an antibiotic prescribed inappropriately. No diagnosis had been captured in patient notes, and the antibiotic chosen was not according to the STG and EML in 30.1% and 31.7% of cases, respectively. Seasonal variation was observed in prescribing adherence, with significantly lower adherence in winter and spring months (adjusted odds ratio 0.60). A reduction of 12.9 DDDs between the pre- and post-intervention periods (p=0.0084) was documented, which represented a 19.3% decrease in antibiotic consumption.Conclusion. The study demonstrated that peer reviewed audit and feedback is an effective AMS intervention to improve antibiotic prescribing in primary care in a low-resource setting. The intervention, utilising existing resources and involving multidisciplinary engagement, may be incorporated into existing quality improvement processes at facility level, to ensure sustainable change

The first accurate parallax distance to a black hole

Using astrometric VLBI observations, we have determined the parallax of the black hole X-ray binary V404 Cyg to be 0.418 +/- 0.024 milliarcseconds, corresponding to a distance of 2.39 +/- 0.14 kpc, significantly lower than the previously accepted value. This model-independent estimate is the most accurate distance to a Galactic stellar-mass black hole measured to date. With this new distance, we confirm that the source was not super-Eddington during its 1989 outburst. The fitted distance and proper motion imply that the black hole in this system likely formed in a supernova, with the peculiar velocity being consistent with a recoil (Blaauw) kick. The size of the quiescent jets inferred to exist in this system is less than 1.4 AU at 22 GHz. Astrometric observations of a larger sample of such systems would provide useful insights into the formation and properties of accreting stellar-mass black holes.Comment: Accepted for publication in ApJ Letters. 6 pages, 2 figure

Flight Demonstration of Novel Atmospheric Satellite Concept

The major focus of the Phase II effort described herein is to develop and demonstrate an aircraft capable of autonomously sailing (i.e., to cruise without propulsion or external assistance), and thereby prove that the dual-aircraft platform (DAP) atmospheric satellite concept is potentially viable. This sailing mode of flight was identified as the number-1 enabling technology required for the stratospheric DAP concept (also known as Stratosat) in the NIAC (NASA Innovative Advanced Concept) Phase I effort. No scientific demonstration of this technology has ever been done or documented to our knowledge. This report describes efforts to take a major step towards the sailing mode of flight capability using a single aircraft connected by cable to a moving ground vehicle which uses sufficient crosswind to cruise without propulsion while "pulling" the ground vehicle forward (i.e., without external assistance). The development of a prototype aircraft is described in terms of novel and key hardware and software elements. A specialized prototype aircraft is described, including a novel cable release mechanism, novel "lateron" control surfaces, and a highly-accurate onboard wind measurement system. Additionally, a novel means to safely connect the aircraft to the moving ground vehicle is described involving a fishing rod/reel and integrated load cell. All of these devices were designed and developed in-house and validated in flight testing. Software is developed to provide look-up tables that give the flight condition targets (i.e., 3-D position relative to ground vehicle, forward speed, aircraft orientation, etc.), based on current wind speed and direction. These tables are successfully validated in flight simulation and used onboard the aircraft. High fidelity analysis of the aircraft aerodynamics are described - required to produce accurate target sailing flight conditions. A novel wind tunnel measurement technique is developed to accurately assess the aerodynamics of the ultra-thin cable. A new specialized flight simulator is described which is utilized to develop and verify the flight software required onboard the aircraft, and to support training of pilots for flying the aircraft while tethered to a ground vehicle. The DAP flight simulator was developed within the Matlab-Simulink framework and included detailed treatment of aircraft/cable aerodynamics, cable dynamics, experimentally-derived propeller-motor thrust curves, actuator responsiveness, and realistic air turbulence. The specialized formation flight controller algorithm, developed using this flight simulator, and onboard the aircraft is described. Finally, a novel auto-tuning software is described and verified within the flight simulator that is shown to refine the sailing flight condition targets during flight using an optimization technique involving doublet maneuvers. Virtual flights using the auto-tuning software indicate that the prototype aircraft should be able to reach and hold sailing conditions despite moderate levels of turbulence provided there is sufficient mean wind available. An overview of the flight testing program is provided. Hundreds of short flights were conducted, primarily using a dead short runway at Deland Municipal Airport which permitted use of a moving ground vehicle. Additional flight tests at Space Floridas Shuttle Landing Facility are also described. First year results from these tests in which the aircraft is controlled manually, demonstrated that excessive flight testing would be required for a pilot to learn to sail with visual cues. However, second year results from autonomous flight these tests included successful demonstration of the closed-loop autonomous formation flight capability (i.e., autonomously determine, reach, and hold the required 3-D location relative to the ground vehicle required for sailing). The next step of using the auto-tune software to autonomously refine the aircraft orientation targets to finally achieve sailing remains the primary goal of future work

Giant Coulomb broadening and Raman lasing on ionic transitions

CW generation of anti-Stokes Raman laser on a number of blue-green argon-ion lines (4p-4s, 4p-3d) has been demonstrated with optical pumping from metastable levels 3d'^2G, 3d^4F. It is found, that the population transfer rate is increased by a factor of 3-5 (and hence, the output power of such Raman laser) owing to Coulomb diffusion in the velocity space. Measured are the excitation and relaxation rates for the metastable level. The Bennett hole on the metastable level has been recorded using the probe field technique. It has been shown that the Coulomb diffusion changes shape of the contour to exponential cusp profile while its width becomes 100 times the Lorentzian one and reaches values close to the Doppler width. Such a giant broadening is also confirmed by the shape of the absorption saturation curve.Comment: RevTex 18 pages, 5 figure

Vocal signals facilitate cooperative hunting in wild chimpanzees

Cooperation and communication likely co-evolved in humans. However, the evolutionary roots of this interdependence remain unclear. We address this issue by investigating the role of vocal signals in facilitating a group cooperative behavior in an ape species: hunting in wild chimpanzees. First, we show that bark vocalizations produced before hunt initiation are reliable signals of behavioral motivation, with barkers being most likely to participate in the hunt. Next, we find that barks are associated with greater hunter recruitment and more effective hunting, with shorter latencies to hunting initiation and prey capture. Our results indicate that the co-evolutionary relationship between vocal communication and group-level cooperation is not unique to humans in the ape lineage, and is likely to have been present in our last common ancestor with chimpanzees