Next-Generation in vivo Modeling of Human Cancers

Animal models of human cancers played a major role in our current understanding of tumor biology. In pre-clinical oncology, animal models empowered drug target and biomarker discovery and validation. In turn, this resulted in improved care for cancer patients. In the quest for understanding and treating a diverse spectrum of cancer types, technological breakthroughs in genetic engineering and single cell “omics” offer tremendous potential to enhance the informative value of pre-clinical models. Here, I review the state-of-the-art in modeling human cancers with focus on animal models for human malignant gliomas. The review highlights the use of glioma models in dissecting mechanisms of tumor initiation, in the retrospective identification of tumor cell-of-origin, in understanding tumor heterogeneity and in testing the potential of immuno-oncology. I build on the deep review of glioma models as a basis for a more general discussion of the potential ways in which transformative technologies may shape the next-generation of pre-clinical models. I argue that refining animal models along the proposed lines will benefit the success rate of translation for pre-clinical research in oncology

Prolegomeni sul dritto romano secondo l'ordine delle instituta dell'Imperatore Giustiniano per uso del privato studio di giurisprudenza / di Gaetano Gargiulo

Prolegomeni sul dritto romano secondo l'ordine delle instituta dell'Imperatore Giustiniano per uso del privato studio di giurisprudenza / di Gaetano Gargiulo Napoli : M. Avallone, 1840 99 p. ; 20 cm

A CNN-based fusion method for feature extraction from sentinel data

Sensitivity to weather conditions, and specially to clouds, is a severe limiting factor to the use of optical remote sensing for Earth monitoring applications. A possible alternative is to benefit from weather-insensitive synthetic aperture radar (SAR) images. In many real-world applications, critical decisions are made based on some informative optical or radar features related to items such as water, vegetation or soil. Under cloudy conditions, however, optical-based features are not available, and they are commonly reconstructed through linear interpolation between data available at temporally-close time instants. In this work, we propose to estimate missing optical features through data fusion and deep-learning. Several sources of information are taken into account—optical sequences, SAR sequences, digital elevation model—so as to exploit both temporal and cross-sensor dependencies. Based on these data and a tiny cloud-free fraction of the target image, a compact convolutional neural network (CNN) is trained to perform the desired estimation. To validate the proposed approach, we focus on the estimation of the normalized difference vegetation index (NDVI), using coupled Sentinel-1 and Sentinel-2 time-series acquired over an agricultural region of Burkina Faso from May–November 2016. Several fusion schemes are considered, causal and non-causal, single-sensor or joint-sensor, corresponding to different operating conditions. Experimental results are very promising, showing a significant gain over baseline methods according to all performance indicators

Chronicle of a death foretold. It is time for echocardiographic screening in young athletes

Abstract Background The novel "Chronicle of a death foretold" by Gabriel Garcia Marquez is a story of a sudden death which could have been prevented. In 1976, within the University of Maryland basketball program and only 8 weeks apart, two athletes died suddenly during physical exertion. They were affected by hypertrophic cardiomyopathy and Marfan syndrome and in both cases an echocardiogram would have prevented the tragic epilogue. This coincidence drew everyone's attention and experts' interest on sudden death in sports. Methods and results Even in recent Italian history, unexpected deaths continue to affect athletes but surprisingly any real knowledge regarding the numbers and the impact of those tragedies must take medical literature and non-medical press into consideration. Herein we report the clinical case of a 13-year-old patient with a bicuspid aortic valve, whose mother was alarmed by the news of a young boy who died because of an anomalous origin of coronary artery (AOCA) which had not been diagnosed at transthoracic echocardiography (TTE). Her obstinacy induced the physicians to repeat TTE and led to the same diagnosis in her son: actually, his right coronary artery originated from the opposite sinus of Valsalva. The suspicion was confirmed by coronary CT scan and, thanks to appropriate therapy, the boy now fares well. Conclusions AOCA is the second most common cause of sudden death in young athletes. Although AOCA is often undetectable at ECG, TTE increases sensitivity of preparticipation screening. It could therefore allow us to avoid such coincidences and prevent sudden juvenile death

A novel broadband forcecardiography sensor for simultaneous monitoring of respiration, infrasonic cardiac vibrations and heart sounds

The precordial mechanical vibrations generated by cardiac contractions have a rich frequency spectrum. While the lowest frequencies can be palpated, the higher infrasonic frequencies are usually captured by the seismocardiogram (SCG) signal and the audible ones correspond to heart sounds. Forcecardiography (FCG) is a non-invasive technique that measures these vibrations via force sensing resistors (FSR). This study presents a new piezoelectric sensor able to record all heart vibrations simultaneously, as well as a respiration signal. The new sensor was compared to the FSR-based one to assess its suitability for FCG. An electrocardiogram (ECG) lead and a signal from an electro-resistive respiration band (ERB) were synchronously acquired as references on six healthy volunteers (4 males, 2 females) at rest. The raw signals from the piezoelectric and the FSR-based sensors turned out to be very similar. The raw signals were divided into four components: Forcerespirogram (FRG), Low-Frequency FCG (LF-FCG), High- Frequency FCG (HF-FCG) and heart sounds (HS-FCG). A beat-by-beat comparison of FCG and ECG signals was carried out by means of regression, correlation and Bland–Altman analyses, and similarly for respiration signals (FRG and ERB). The results showed that the infrasonic FCG components are strongly related to the cardiac cycle (R2 > 0.999, null bias and Limits of Agreement (LoA) of ± 4.9 ms for HF-FCG; R2 > 0.99, null bias and LoA of ± 26.9 ms for LF-FCG) and the FRG inter-breath intervals are consistent with ERB ones (R2 > 0.99, non-significant bias and LoA of ± 0.46 s). Furthermore, the piezoelectric sensor was tested against an accelerometer and an electronic stethoscope: synchronous acquisitions were performed to quantify the similarity between the signals. ECG-triggered ensemble averages (synchronized with R-peaks) of HF-FCG and SCG showed a correlation greater than 0.81, while those of HS-FCG and PCG scored a correlation greater than 0.85. The piezoelectric sensor demonstrated superior performances as compared to the FSR, providing more accurate, beat-by-beat measurements. This is the first time that a single piezoelectric sensor demonstrated the ability to simultaneously capture respiration, heart sounds, an SCG-like signal (i.e., HF-FCG) and the LF-FCG signal, which may provide information on ventricular emptying and filling events. According to these preliminary results the novel piezoelectric FCG sensor stands as a promising device for accurate, unobtrusive, long-term monitoring of cardiorespiratory functions and paves the way for a wide range of potential applications, both in the research and clinical fields. However, these results should be confirmed by further analyses on a larger cohort of subjects, possibly including also pathological patients

Continuous vital monitoring during sleep and light activity using carbon-black elastomer sensors

The comfortable, continuous monitoring of vital parameters is still a challenge. The long-term measurement of respiration and cardiovascular signals is required to diagnose cardiovascular and respiratory diseases. Similarly, sleep quality assessment and the recovery period following acute treatments require long-term vital parameter datalogging. To address these requirements, we have developed “VitalCore”, a wearable continuous vital parameter monitoring device in the form of a T-shirt targeting the uninterrupted monitoring of respiration, pulse, and actigraphy. VitalCore uses polymer-based stretchable resistive bands as the primary sensor to capture breathing and pulse patterns from chest expansion. The carbon black-impregnated polymer is implemented in a U-shaped configuration and attached to the T-shirt with “interfacing” material along with the accompanying electronics. In this paper, VitalCore is bench tested and compared to gold standard respiration and pulse measurements to verify its functionality and further to assess the quality of data captured during sleep and during light exercise (walking). We show that these polymer-based sensors could identify respiratory peaks with a sensitivity of 99.44%, precision of 96.23%, and false-negative rate of 0.557% during sleep. We also show that this T-shirt configuration allows the wearer to sleep in all sleeping positions with a negligible difference of data quality. The device was also able to capture breathing during gait with 88.9%–100% accuracy in respiratory peak detection

Ross-Kabbani Operation in an Infant with Mitral Valve Dysplasia

Background. Mitral valve replacement can be very difficult to obtain in infants because the valve annulus diameter can be smaller than the available prosthesis. Case Report. We describe the case of a 2-month-old female weighing 3.5 kg affected by mitral valve dysplasia leading to severe valve stenosis. Despite full medication, the clinical conditions were critical and surgery was undertaken. The mitral valve was unsuitable for repair and the orifice of mitral anulus was 12 mm, too small for a mechanical prosthesis. Therefore, a Ross-Kabbani operation was undertaken, replacing the mitral valve with the pulmonary autograft and reconstructing the right ventricular outflow tract with an etherograft. Results. The postoperative course was uneventful and the clinical conditions are good at 4-month follow-up. Conclusion. The Ross-Kabbani operation can be an interesting alternative to mitral valve replacement in infants when valve repair is not achievable and there is little space for an intra-annular mechanical prosthesis implant

Laparoscopic robotic surgery : current perspective and future directions

Just as laparoscopic surgery provided a giant leap in safety and recovery for patients over open surgery methods, robotic-assisted surgery (RAS) is doing the same to laparoscopic surgery. The first laparoscopic-RAS systems to be commercialized were the Intuitive Surgical, Inc. da Vinci and the Computer Motion Zeus. These systems were similar in many aspects, which led to a patent dispute between the two companies. Before the dispute was settled in court, Intuitive Surgical bought Computer Motion, and thus owned critical patents for laparoscopic-RAS. Recently, the patents held by Intuitive Surgical have begun to expire, leading to many new laparoscopic-RAS systems being developed and entering the market. In this study, we review the newly commercialized and prototype laparoscopic-RAS systems. We compare the features of the imaging and display technology, surgeons console and patient cart of the reviewed RAS systems. We also briefly discuss the future directions of laparoscopic-RAS surgery. With new laparoscopic-RAS systems now commercially available we should see RAS being adopted more widely in surgical interventions and costs of procedures using RAS to decrease in the near future

Low-power transcutaneous current stimulator for wearable applications

BACKGROUND: Peripheral neuropathic desensitization associated with aging, diabetes, alcoholism and HIV/AIDS, affects tens of millions of people worldwide, and there is little or no treatment available to improve sensory function. Recent studies that apply imperceptible continuous vibration or electrical stimulation have shown promise in improving sensitivity in both diseased and healthy participants. This class of interventions only has an effect during application, necessitating the design of a wearable device for everyday use. We present a circuit that allows for a low-power, low-cost and small form factor implementation of a current stimulator for the continuous application of subthreshold currents. RESULTS: This circuit acts as a voltage-to-current converter and has been tested to drive + 1 to - 1 mA into a 60 k[Formula: see text] load from DC to 1 kHz. Driving a 60 k[Formula: see text] load with a 2 mA peak-to-peak 1 kHz sinusoid, the circuit draws less than 21 mA from a 9 V source. The minimum operating current of the circuit is less than 12 mA. Voltage compliance is ± 60 V with just 1.02 mA drawn by the high voltage current drive circuitry. The circuit was implemented as a compact 46 mm × 21 mm two-layer PCB highlighting its potential for use in a body-worn device. CONCLUSIONS: No design to the best of our knowledge presents comparably low quiescent power with such high voltage compliance. This makes the design uniquely appropriate for low-power transcutaneous current stimulation in wearable applications. Further development of driving and instrumentation circuitry is recommended

Ross-kabbani operation in an infant with mitral valve dysplasia.

Background. Mitral valve replacement can be very difficult to obtain in infants because the valve annulus diameter can be smaller than the available prosthesis. Case Report. We describe the case of a 2-month-old female weighing 3.5 kg affected by mitral valve dysplasia leading to severe valve stenosis. Despite full medication, the clinical conditions were critical and surgery was undertaken. The mitral valve was unsuitable for repair and the orifice of mitral anulus was 12 mm, too small for a mechanical prosthesis. Therefore, a Ross-Kabbani operation was undertaken, replacing the mitral valve with the pulmonary autograft and reconstructing the right ventricular outflow tract with an etherograft. Results. The postoperative course was uneventful and the clinical conditions are good at 4-month follow-up. Conclusion. The Ross-Kabbani operation can be an interesting alternative to mitral valve replacement in infants when valve repair is not achievable and there is little space for an intra-annular mechanical prosthesis implant