Organic electrochemical networks for biocompatible and implantable machine learning: Organic bioelectronic beyond sensing

How can the brain be such a good computer? Part of the answer lies in the astonishing number of neurons and synapses that process electrical impulses in parallel. Part of it must be found in the ability of the nervous system to evolve in response to external stimuli and grow, sharpen, and depress synaptic connections. However, we are far from understanding even the basic mechanisms that allow us to think, be aware, recognize patterns, and imagine. The brain can do all this while consuming only around 20 Watts, out-competing any human-made processor in terms of energy-efficiency. This question is of particular interest in a historical era and technological stage where phrases like machine learning and artificial intelligence are more and more widespread, thanks to recent advances produced in the field of computer science. However, brain-inspired computation is today still relying on algorithms that run on traditional silicon-made, digital processors. Instead, the making of brain-like hardware, where the substrate itself can be used for computation and it can dynamically update its electrical pathways, is still challenging. In this work, I tried to employ organic semiconductors that work in electrolytic solutions, called organic mixed ionic-electronic conductors (OMIECs) to build hardware capable of computation. Moreover, by exploiting an electropolymerization technique, I could form conducting connections in response to electrical spikes, in analogy to how synapses evolve when the neuron fires. After demonstrating artificial synapses as a potential building block for neuromorphic chips, I shifted my attention to the implementation of such synapses in fully operational networks. In doing so, I borrowed the mathematical framework of a machine learning approach known as reservoir computing, which allows computation with random (neural) networks. I capitalized my work on demonstrating the possibility of using such networks in-vivo for the recognition and classification of dangerous and healthy heartbeats. This is the first demonstration of machine learning carried out in a biological environment with a biocompatible substrate. The implications of this technology are straightforward: a constant monitoring of biological signals and fluids accompanied by an active recognition of the presence of malign patterns may lead to a timely, targeted and early diagnosis of potentially mortal conditions. Finally, in the attempt to simulate the random neural networks, I faced difficulties in the modeling of the devices with the state-of-the-art approach. Therefore, I tried to explore a new way to describe OMIECs and OMIECs-based devices, starting from thermodynamic axioms. The results of this model shine a light on the mechanism behind the operation of the organic electrochemical transistors, revealing the importance of the entropy of mixing and suggesting new pathways for device optimization for targeted applications

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Organic electrochemical networks for biocompatible and implantable machine learning: Organic bioelectronic beyond sensing

How can the brain be such a good computer? Part of the answer lies in the astonishing number of neurons and synapses that process electrical impulses in parallel. Part of it must be found in the ability of the nervous system to evolve in response to external stimuli and grow, sharpen, and depress synaptic connections. However, we are far from understanding even the basic mechanisms that allow us to think, be aware, recognize patterns, and imagine. The brain can do all this while consuming only around 20 Watts, out-competing any human-made processor in terms of energy-efficiency. This question is of particular interest in a historical era and technological stage where phrases like machine learning and artificial intelligence are more and more widespread, thanks to recent advances produced in the field of computer science. However, brain-inspired computation is today still relying on algorithms that run on traditional silicon-made, digital processors. Instead, the making of brain-like hardware, where the substrate itself can be used for computation and it can dynamically update its electrical pathways, is still challenging. In this work, I tried to employ organic semiconductors that work in electrolytic solutions, called organic mixed ionic-electronic conductors (OMIECs) to build hardware capable of computation. Moreover, by exploiting an electropolymerization technique, I could form conducting connections in response to electrical spikes, in analogy to how synapses evolve when the neuron fires. After demonstrating artificial synapses as a potential building block for neuromorphic chips, I shifted my attention to the implementation of such synapses in fully operational networks. In doing so, I borrowed the mathematical framework of a machine learning approach known as reservoir computing, which allows computation with random (neural) networks. I capitalized my work on demonstrating the possibility of using such networks in-vivo for the recognition and classification of dangerous and healthy heartbeats. This is the first demonstration of machine learning carried out in a biological environment with a biocompatible substrate. The implications of this technology are straightforward: a constant monitoring of biological signals and fluids accompanied by an active recognition of the presence of malign patterns may lead to a timely, targeted and early diagnosis of potentially mortal conditions. Finally, in the attempt to simulate the random neural networks, I faced difficulties in the modeling of the devices with the state-of-the-art approach. Therefore, I tried to explore a new way to describe OMIECs and OMIECs-based devices, starting from thermodynamic axioms. The results of this model shine a light on the mechanism behind the operation of the organic electrochemical transistors, revealing the importance of the entropy of mixing and suggesting new pathways for device optimization for targeted applications

Organic electrochemical networks for biocompatible and implantable machine learning: Organic bioelectronic beyond sensing

How can the brain be such a good computer? Part of the answer lies in the astonishing number of neurons and synapses that process electrical impulses in parallel. Part of it must be found in the ability of the nervous system to evolve in response to external stimuli and grow, sharpen, and depress synaptic connections. However, we are far from understanding even the basic mechanisms that allow us to think, be aware, recognize patterns, and imagine. The brain can do all this while consuming only around 20 Watts, out-competing any human-made processor in terms of energy-efficiency. This question is of particular interest in a historical era and technological stage where phrases like machine learning and artificial intelligence are more and more widespread, thanks to recent advances produced in the field of computer science. However, brain-inspired computation is today still relying on algorithms that run on traditional silicon-made, digital processors. Instead, the making of brain-like hardware, where the substrate itself can be used for computation and it can dynamically update its electrical pathways, is still challenging. In this work, I tried to employ organic semiconductors that work in electrolytic solutions, called organic mixed ionic-electronic conductors (OMIECs) to build hardware capable of computation. Moreover, by exploiting an electropolymerization technique, I could form conducting connections in response to electrical spikes, in analogy to how synapses evolve when the neuron fires. After demonstrating artificial synapses as a potential building block for neuromorphic chips, I shifted my attention to the implementation of such synapses in fully operational networks. In doing so, I borrowed the mathematical framework of a machine learning approach known as reservoir computing, which allows computation with random (neural) networks. I capitalized my work on demonstrating the possibility of using such networks in-vivo for the recognition and classification of dangerous and healthy heartbeats. This is the first demonstration of machine learning carried out in a biological environment with a biocompatible substrate. The implications of this technology are straightforward: a constant monitoring of biological signals and fluids accompanied by an active recognition of the presence of malign patterns may lead to a timely, targeted and early diagnosis of potentially mortal conditions. Finally, in the attempt to simulate the random neural networks, I faced difficulties in the modeling of the devices with the state-of-the-art approach. Therefore, I tried to explore a new way to describe OMIECs and OMIECs-based devices, starting from thermodynamic axioms. The results of this model shine a light on the mechanism behind the operation of the organic electrochemical transistors, revealing the importance of the entropy of mixing and suggesting new pathways for device optimization for targeted applications

Hands-on reservoir computing: a tutorial for practical implementation

International audienceAbstract This manuscript serves a specific purpose: to give readers from fields such as material science, chemistry, or electronics an overview of implementing a reservoir computing (RC) experiment with her/his material system. Introductory literature on the topic is rare and the vast majority of reviews puts forth the basics of RC taking for granted concepts that may be nontrivial to someone unfamiliar with the machine learning field (see for example reference Lukoševičius (2012 Neural Networks: Tricks of the Trade (Berlin: Springer) pp 659–686). This is unfortunate considering the large pool of material systems that show nonlinear behavior and short-term memory that may be harnessed to design novel computational paradigms. RC offers a framework for computing with material systems that circumvents typical problems that arise when implementing traditional, fully fledged feedforward neural networks on hardware, such as minimal device-to-device variability and control over each unit/neuron and connection. Instead, one can use a random, untrained reservoir where only the output layer is optimized, for example, with linear regression. In the following, we will highlight the potential of RC for hardware-based neural networks, the advantages over more traditional approaches, and the obstacles to overcome for their implementation. Preparing a high-dimensional nonlinear system as a well-performing reservoir for a specific task is not as easy as it seems at first sight. We hope this tutorial will lower the barrier for scientists attempting to exploit their nonlinear systems for computational tasks typically carried out in the fields of machine learning and artificial intelligence. A simulation tool to accompany this paper is available online 7 7 https://github.com/stevenabreu7/handson_reservoir .

In Liquido Computation with Electrochemical Transistors and Mixed Conductors for Intelligent Bioelectronics

Next-generation implantable computational devices require long-term-stable electronic components capable of operating in, and interacting with, electrolytic surroundings without being damaged. Organic electrochemical transistors (OECTs) emerged as fitting candidates. However, while single devices feature impressive figures of merit, integrated circuits (ICs) immersed in common electrolytes are hard to realize using electrochemical transistors, and there is no clear path forward for optimal top-down circuit design and high-density integration. The simple observation that two OECTs immersed in the same electrolytic medium will inevitably interact hampers their implementation in complex circuitry. The electrolytes ionic conductivity connects all the devices in the liquid, producing unwanted and often unforeseeable dynamics. Minimizing or harnessing this crosstalk has been the focus of very recent studies. Herein, the main challenges, trends, and opportunities for realizing OECT-based circuitry in a liquid environment that could circumnavigate the hard limits of engineering and human physiology, are discussed. The most successful approaches in autonomous bioelectronics and information processing are analyzed. Elaborating on the strategies to circumvent and harness device crosstalk proves that platforms capable of complex computation and even machine learning (ML) can be realized in liquido using mixed ionic-electronic conductors (OMIECs).Funding Agencies|Swedish Research Council [VR-2017-04910]; Swedish Foundation For Strategic Research [FFL18-0101]; Bundesministerium fur Bildung und Forschung (BMBF) [01IS21089]; Ecole Polytechnique Federale de Lausanne</p

Surgical treatment for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma is an aggressive tumor usually discovered at an advanced stage. Surgical resection is the treatment of choice but less than 50% of patients may receive curative resection. In almost 70% of patients, extended hepatectomy with vascular resection and/or bile duct resection are required to achieve a negative margin. Overall 5-year survival is around 30%. Prognosis is mainly based on tumor factors such as size, number, lymph node or vascular invasion and surgical margin. The main sites of recurrence are the liver, peritoneum and lymph nodes. In patients with liver-only recurrence, re-resection should always be considered.Intrahepatic cholangiocarcinoma is an aggressive tumor usually discovered at an advanced stage. Surgical resection is the treatment of choice but less than 50% of patients may receive curative resection. In almost 70% of patients, extended hepatectomy with vascular resection and/or bile duct resection are required to achieve a negative margin. Overall 5-year survival is around 30%. Prognosis is mainly based on tumor factors such as size, number, lymph node or vascular invasion and surgical margin. The main sites of recurrence are the liver, peritoneum and lymph nodes. In patients with liver-only recurrence, re-resection should always be considered

A Methodology for Modeling the Cat-Heating Transient Phase in a Turbocharged Direct Injection Spark Ignition Engine

This paper presents the modeling of the transient phase of catalyst heating on a high-performance turbocharged spark ignition engine with the aim to accurately predict the exhaust thermal energy available at the catalyst inlet and to provide a "virtual test rig" to assess different design and calibration options.The entire transient phase, starting from the engine cranking until the catalyst warm-up is completed, was taken into account in the simulation, and the model was validated using a wide data-set of experimental tests.The first step of the modeling activity was the combustion analysis during the transient phase: the burn rate was evaluated on the basis of experimental in-cylinder pressure data, considering both cycle-to-cycle and cylinder-to-cylinder variations.Then, as far as the exhaust temperatures are concerned, a detailed model of the thermocouples was implemented to replicate the physical behavior of the sensors during the warm-up and to compare the simulated temperatures with the measured ones.Finally, a complete analysis of the energy balance during the transient was carried out: the thermal power available to the catalyst inlet was obtained from a complete analysis of power losses (i.e. friction and pumping losses, in-cylinder heat transfer, engine block and engine coolant heating, exhaust manifold heat transfer, etc.).In conclusion, the proposed methodology allows to reliably simulate in details the Cat-Heating transient, showing a valuable potential in driving the main design and calibration choices during the engine development process

Thermodynamics of organic electrochemical transistors

Despite their increasing usefulness in a wide variety of applications, organic electrochemical transistors still lack a comprehensive and unifying physical framework able to describe the current-voltage characteristics and the polymer/electrolyte interactions simultaneously. Building upon thermodynamic axioms, we present a quantitative analysis of the operation of organic electrochemical transistors. We reveal that the entropy of mixing is the main driving force behind the redox mechanism that rules the transfer properties of such devices in electrolytic environments. In the light of these findings, we show that traditional models used for organic electrochemical transistors, based on the theory of field-effect transistors, fall short as they treat the active material as a simple capacitor while ignoring the material properties and energetic interactions. Finally, by analyzing a large spectrum of solvents and device regimes, we quantify the entropic and enthalpic contributions and put forward an approach for targeted material design and device applications