Improving access to cancer clinical research in Brazil: recent advances and new opportunities. Expert opinions from the 4th CURA meeting, São Paulo, 2023.

Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil.

Artificial optoelectronic spiking neuron based on a resonant tunnelling diode coupled to a vertical cavity surface emitting laser.

Excitable optoelectronic devices represent one of the key building blocks for implementation of artificial spiking neurons in neuromorphic (brain-inspired) photonic systems. This work introduces and experimentally investigates an opto-electro-optical (O/E/O) artificial neuron built with a resonant tunnelling diode (RTD) coupled to a photodetector as a receiver and a vertical cavity surface emitting laser as a transmitter. We demonstrate a well-defined excitability threshold, above which the neuron produces optical spiking responses with characteristic neural-like refractory period. We utilise its fan-in capability to perform in-device coincidence detection (logical AND) and exclusive logical OR (XOR) tasks. These results provide first experimental validation of deterministic triggering and tasks in an RTD-based spiking optoelectronic neuron with both input and output optical (I/O) terminals. Furthermore, we also investigate in simulation the prospects of the proposed system for nanophotonic implementation in a monolithic design combining a nanoscale RTD element and a nanolaser; therefore demonstrating the potential of integrated RTD-based excitable nodes for low footprint, high-speed optoelectronic spiking neurons in future neuromorphic photonic hardware.

Delay dynamics of neuromorphic optoelectronic nanoscale resonators: Perspectives and applications.

With the recent exponential growth of applications using artificial intelligence (AI), the development of efficient and ultrafast brain-like (neuromorphic) systems is crucial for future information and communication technologies. While the implementation of AI systems using computer algorithms of neural networks is emerging rapidly, scientists are just taking the very first steps in the development of the hardware elements of an artificial brain, specifically neuromorphic microchips. In this review article, we present the current state of the art of neuromorphic photonic circuits based on solid-state optoelectronic oscillators formed by nanoscale double barrier quantum well resonant tunneling diodes. We address, both experimentally and theoretically, the key dynamic properties of recently developed artificial solid-state neuron microchips with delayed perturbations and describe their role in the study of neural activity and regenerative memory. This review covers our recent research work on excitable and delay dynamic characteristics of both single and autaptic (delayed) artificial neurons including all-or-none response, spike-based data encoding, storage, signal regeneration and signal healing. Furthermore, the neural responses of these neuromorphic microchips display all the signatures of extended spatio-temporal localized structures (LSs) of light, which are reviewed here in detail. By taking advantage of the dissipative nature of LSs, we demonstrate potential applications in optical data reconfiguration and clock and timing at high-speeds and with short transients. The results reviewed in this article are a key enabler for the development of high-performance optoelectronic devices in future high-speed brain-inspired optical memories and neuromorphic computing.

Regenerative memory in time-delayed neuromorphic photonic resonators.

We investigate a photonic regenerative memory based upon a neuromorphic oscillator with a delayed self-feedback (autaptic) connection. We disclose the existence of a unique temporal response characteristic of localized structures enabling an ideal support for bits in an optical buffer memory for storage and reshaping of data information. We link our experimental implementation, based upon a nanoscale nonlinear resonant tunneling diode driving a laser, to the paradigm of neuronal activity, the FitzHugh-Nagumo model with delayed feedback. This proof-of-concept photonic regenerative memory might constitute a building block for a new class of neuron-inspired photonic memories that can handle high bit-rate optical signals.

Excitability and optical pulse generation in semiconductor lasers driven by resonant tunneling diode photo-detectors.

We demonstrate, experimentally and theoretically, excitable nanosecond optical pulses in optoelectronic integrated circuits operating at telecommunication wavelengths (1550 nm) comprising a nanoscale double barrier quantum well resonant tunneling diode (RTD) photo-detector driving a laser diode (LD). When perturbed either electrically or optically by an input signal above a certain threshold, the optoelectronic circuit generates short electrical and optical excitable pulses mimicking the spiking behavior of biological neurons. Interestingly, the asymmetric nonlinear characteristic of the RTD-LD allows for two different regimes where one obtain either single pulses or a burst of multiple pulses. The high-speed excitable response capabilities are promising for neurally inspired information applications in photonics.

Photo-detectors integrated with resonant tunneling diodes.

We report on photo-detectors consisting of an optical waveguide that incorporates a resonant tunneling diode (RTD). Operating at wavelengths around 1.55 µm in the optical communications C band we achieve maximum sensitivities of around 0.29 A/W which is dependent on the bias voltage. This is due to the nature of RTD nonlinear current-voltage characteristic that has a negative differential resistance (NDR) region. The resonant tunneling diode photo-detector (RTD-PD) can be operated in either non-oscillating or oscillating regimes depending on the bias voltage quiescent point. The oscillating regime is apparent when the RTD-PD is biased in the NDR region giving rise to electrical gain and microwave self-sustained oscillations Taking advantage of the RTD's NDR distinctive characteristics, we demonstrate efficient detection of gigahertz (GHz) modulated optical carriers and optical control of a RTD GHz oscillator. RTD-PD based devices can have applications in generation and optical control of GHz low-phase noise oscillators, clock recovery systems, and fiber optic enabled radio frequency communication systems.

Nonlinear conductivity of fullerenol aqueous solutions.

Fullerenols have been a subject of intense research in many fields with the claim of possible applications in biomedicine such as free-radical sponges, antioxidants, and photosensitizers. However, its transport characteristics, important in determining the feasibility of many applications, have not been studied yet. In this work, electrochemical impedance of aqueous solutions of two types of fullerenols (C(60)(OH)(22-26) and C(60)(OH)(18-22)(OK)(4)) was measured. Sample conductivity was extracted from impedance data, and a nonlinear concentration-dependent conductivity was found for one of two types (C(60)(OH)(18-22)(OK)(4)). A concentration-dependent mobility that accounts electrophoretic and relaxation effects could explain experimental data. As a result, we obtained some fullerenol parameters, relevant to transport phenomena: its hydrodynamic radius, the number of attached hydroxides, and the number of counterions solvated into solution. In addition, an important result for pharmaceutical applications has been discussed, which is the change of pH in water induced by the different concentrations of fullerenol, indicating it behaves as a weak acid.

A Self-Synchronized Optoelectronic Oscillator based on an RTD Photo-Detector and a Laser Diode.

We propose and demonstrate a simple and stable low-phase noise optoelectronic oscillator (OEO) that uses a laser diode, an optical fiber delay line and a resonant tunneling diode (RTD) free-running oscillator that is monolithic integrated with a waveguide photo-detector. The RTD-OEO exhibits single-side band phase noise power below -100 dBc/Hz with more than 30 dB noise suppression at 10 kHz from the center free-running frequency for fiber loop lengths around 1.2 km. The oscillator power consumption is below 0.55 W, and can be controlled either by the injected optical power or the fiber delay line. The RTD-OEO stability is achieved without using other high-speed optical/optoelectronic components and amplification.