Increasing the Capacity of Primary Care Through Enabling Technology.

Primary care is the foundation of effective and high-quality health care. The role of primary care clinicians has expanded to encompass coordination of care across multiple providers and management of more patients with complex conditions. Enabling technology has the potential to expand the capacity for primary care clinicians to provide integrated, accessible care that channels expertise to the patient and brings specialty consultations into the primary care clinic. Furthermore, technology offers opportunities to engage patients in advancing their health through improved communication and enhanced self-management of chronic conditions. This paper describes enabling technologies in four domains (the body, the home, the community, and the primary care clinic) that can support the critical role primary care clinicians play in the health care system. It also identifies challenges to incorporating these technologies into primary care clinics, care processes, and workflow

Will cryptographically enhanced commerce lead to a better world or make it more unequal?

Web 3.0 is meant to describe a new set of technology developments for the internet that are moving the pendulum back to a more decentralised environment, away from walled gardens such as Apple, Facebook, and Google. But the jury is still out on whether cryptographically enhanced commerce will be positive or negative for improving equity, diversity, and inclusion in societies and organisations. Thomas Kalafatis and Richard Nesbitt explain how having a better world or a more unequal one depends on how cryptographically enabled techniques are rolled out across software and finance

Flight Test Results for Uniquely Tailored Propulsion-Airframe Aeroacoustic Chevrons: Shockcell Noise

Azimuthally varying chevrons (AVC) which have been uniquely tailored to account for the asymmetric propulsion-airframe aeroacoustic interactions have recently shown significant reductions in jet-related community noise at low-speed take-off conditions in scale model tests of coaxial nozzles with high bypass ratio. There were indications that such AVCs may also provide shockcell noise reductions at high cruise speeds. This paper describes the flight test results when one such AVC concept, namely, the T-fan chevrons with enhanced mixing near the pylon, was tested at full-scale on a modern large twin-jet aircraft (777-300ER) with focus on shockcell noise at mid-cruise conditions. Shockcell noise is part of the interior cabin noise at cruise conditions and its reduction is useful from the viewpoint of passenger comfort. Noise reduction at the source, in the exhaust jet, especially, at low frequencies, is beneficial from the perspective of reduced fuselage sidewall acoustic lining. Results are shown in terms of unsteady pressure spectra both on the exterior surface of the fuselage at several axial stations and also microphone arrays placed inside the fuselage aft of the engine. The benefits of T-fan chevrons, with and without conventional chevrons on the core nozzle, are shown for several engine operating conditions at cruise involving supersonic fan stream and subsonic or supersonic core stream. The T-fan AVC alone provides up to 5 dB low-frequency noise reduction on the fuselage exterior skin and up to 2 dB reduction inside the cabin. Addition of core chevrons appears to increase the higher frequency noise. This flight test result with the previous model test observation that the T-fan AVCs have hardly any cruise thrust coefficient loss (< 0.05%) make them viable candidates for reducing interior cabin noise in high bypass ratio engines

Flight Test Results for Uniquely Tailored Propulsion-Airframe Aeroacoustic Chevrons: Community Noise

The flow/acoustic environment around the jet exhaust of an engine when installed on an airplane, say, under the wing, is highly asymmetric due to the pylon, the wing and the high-lift devices. Recent scale model tests have shown that such Propulsion Airframe Aeroacoustic (PAA) interactions and the jet mixing noise can be reduced more than with conventional azimuthally uniform chevrons by uniquely tailoring the chevrons to produce enhanced mixing near the pylon. This paper describes the community noise results from a flight test on a large twin-engine airplane using this concept of azimuthally varying chevrons for engines installed under the wing. Results for two different nozzle configurations are described: azimuthally varying "PAA T-fan" chevrons on the fan nozzle with a baseline no-chevron core nozzle and a second with PAA T-fan chevrons with conventional azimuthally uniform chevrons on the core nozzle. We analyze these test results in comparison to the baseline no-chevron nozzle on both spectral and integrated power level bases. The study focuses on the peak jet noise reduction and the effects at high frequencies for typical take-off power settings. The noise reduction and the absolute noise levels are then compared to model scale results. The flight test results verify that the PAA T-fan nozzles in combination with standard core chevron nozzles can, indeed, give a reasonable amount of noise reduction at low frequencies without high-frequency lift during take-off conditions and hardly any impact on the cruise thrust coefficient

Targeted Chemo-Sonodynamic Therapy Treatment of Breast Tumours Using Ultrasound Responsive Microbubbles Loaded with Paclitaxel, Doxorubicin and Rose Bengal.

Mastectomy is a common surgical treatment used in the management of breast cancer but has associated physical and psychological consequences for the patient. Breast conservation surgery (BCS) is an alternative to mastectomy but is only possible when the tumour is of an appropriate size. Neo-adjuvant chemotherapy has been successfully used to downstage tumours and increase the number of patients eligible for BCS. However, the chemotherapies used in this approach are non-targeted and often result in significant side effects to the patient. In this manuscript, we evaluate the potential of ultrasound targeted microbubble destruction (UTMD) to deliver Rose Bengal-mediated sonodynamic therapy (SDT) in combination with paclitaxel (PTX) and doxorubicin (Dox) chemotherapy as a potential treatment for breast cancer. Efficacy of the combined treatment was determined in a three-dimensional (3D) spheroid model of human breast cancer and in a murine model of the disease bearing subcutaneous MCF-7 tumours. The results demonstrated a significant reduction in both the cell viability of spheroids and tumour volume following treatment with the drug loaded microbubbles and ultrasound compared to targets treated with the drug loaded microbubbles alone or a Cremophor EL suspension of PTX and Dox. In addition, the weight of animals that received the microbubble treatment was unchanged throughout the study while a reduction of 12.1% was observed for animals treated with a Cremophor suspension of PTX/Dox. These results suggest that UTMD-mediated chemo-sonodynamic therapy is an efficacious and well tolerated approach for the treatment of breast cancer

GABA-ergic Dynamics in Human Frontotemporal Networks Confirmed by Pharmaco-Magnetoencephalography.

To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked 'mismatch negativity' response and transiently induced oscillations. Here, we probe GABAergic influences in the networks using double-blind placebo-controlled randomized-crossover administration of the GABA reuptake inhibitor, tiagabine (oral, 10 mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both drug sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. We found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco- magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.SIGNIFICANCE STATEMENT Understanding human brain function and developing new treatments require good models of brain function. We tested a detailed generative model of cortical microcircuits that accurately reproduced human magnetoencephalography, to quantify network dynamics and connectivity in frontotemporal cortex. This approach identified the effect of a test drug (GABA-reuptake inhibitor, tiagabine) on neuronal function (GABA-ergic dynamics), opening the way for psychopharmacological studies in health and disease with the mechanistic precision afforded by generative models of the brain