Time delay reservoir computing with a silicon microring resonator and a fiber-based optical feedback loop.

Silicon microring resonators serve as critical components in integrated photonic neural network implementations, owing to their compact footprint, compatibility with CMOS technology, and passive nonlinear dynamics. Recent advancements have leveraged their filtering properties as weighting functions, and their nonlinear dynamics as activation functions with spiking capabilities. In this work, we investigate experimentally the linear and nonlinear dynamics of microring resonators for time delay reservoir computing, by introducing an external optical feedback loop. After effectively mitigating the impact of environmental noise on the fiber-based feedback phase dependencies, we evaluate the computational capacity of this system by assessing its performance across various benchmark tasks at a bit rate of few Mbps. We show that the additional memory provided by the optical feedback is necessary to achieve error-free operation in delayed-boolean tasks that require up to 3 bits of memory. In this case the microring was operated in the linear regime and the photodetection was the nonlinear activation function. We also show that the Santa Fe and Mackey Glass prediction tasks are solved when the microring nonlinearities are activated. Notably, our study reveals competitive outcomes even when employing only 7 virtual nodes within our photonic reservoir. Our findings illustrate the silicon microring's versatile performance in the presence of optical feedback, highlighting its ability to be tailored for various computing applications.

Elevated Interleukin-6 Levels Are Associated With an Increased Risk of QTc Interval Prolongation in a Large Cohort of US Veterans.

BACKGROUND: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects. METHODS AND RESULTS: An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (<5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (>25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc >470 ms men/480 ms women ms: odds ratio, 2.28 [95% CI, 1.12-4.50] for IL-6 >25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 >25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction. CONCLUSIONS: Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population.

A Convolutional Neural Network for Electrical Fault Recognition in Active Magnetic Bearing Systems.

Active magnetic bearings are complex mechatronic systems that consist of mechanical, electrical, and software parts, unlike classical rolling bearings. Given the complexity of this type of system, fault detection is a critical process. This paper presents a new and easy way to detect faults based on the use of a fault dictionary and machine learning. The dictionary was built starting from fault signatures consisting of images obtained from the signals available in the system. Subsequently, a convolutional neural network was trained to recognize such fault signature images. The objective of this study was to develop a fault dictionary and a classifier to recognize the most frequent soft electrical faults that affect position sensors and actuators. The proposed method permits, in a computationally convenient way that can be implemented in real time, the determination of which component has failed and what kind of failure has occurred. Therefore, this fault identification system allows determining which countermeasure to adopt in order to enhance the reliability of the system. The performance of this method was assessed by means of a case study concerning a real turbomachine supported by two active magnetic bearings for the oil and gas field. Seventeen fault classes were considered, and the neural network fault classifier reached an accuracy of 93% on the test dataset.

Microring resonators with external optical feedback for time delay reservoir computing.

Microring resonators (MRRs) are a key photonic component in integrated devices, due to their small size, low insertion losses, and passive operation. While the MRRs have been established for optical filtering in wavelength-multiplexed systems, the nonlinear properties that they can exhibit give rise to new perspectives on their use. For instance, they have been recently considered for introducing optical nonlinearity in photonic reservoir computing systems. In this work, we present a detailed numerical investigation of a silicon MRR operation, in the presence of external optical feedback, in a time delay reservoir computing scheme. We demonstrate the versatility of this compact, passive device, by exploiting different operating regimes and solving computing tasks with diverse memory requirements. We show that when large memory is required, as it occurs in the Narma 10 task, the MRR nonlinearity does not play a significant role when the photodetection nonlinearity is involved, while the contribution of the external feedback is significant. On the contrary, for computing tasks such as the Mackey-Glass and the Santa Fe chaotic timeseries prediction, the MRR and the photodetection nonlinearities contribute both to efficient computation. The presence of optical feedback improves the prediction of the Mackey-Glass timeseries while it plays a minor role in the Santa Fe timeseries case.

Survival in acute heart failure in intensive cardiac care unit: a prospective study.

The aim of this study is to identify the best predictors of mortality among clinical, biochemical and advanced echocardiographic parameters in acute heart failure (AHF) patients admitted to coronary care unit (CCU). AHF is a clinical condition characterized by high mortality and morbidity. Several studies have investigated the potential prognostic factors that could help the risk assessment of cardiovascular events in HF patients, but at the moment it has not been found a complete prognostic score (including clinical, laboratory and echocardiographic parameters), univocally used for AHF patients. Patients (n = 118) admitted to CCU due to AHF de novo or to an exacerbation of chronic heart failure were enrolled. For each patient, clinical and biochemical parameters were reported as well as the echocardiographic data, including speckle tracking echocardiography analysis. These indexes were then related to intra- and extrahospital mortality. At the end of the follow-up period, the study population was divided into two groups, defined as 'survivors' and 'non-survivors'. From statistical analysis, C-reactive protein (CRP) (AUC = 0.75), haemoglobin (AUC = 0.71), creatinine clearance (AUC = 0.74), left atrial strain (AUC = 0.73) and freewall right ventricular strain (AUC = 0.76) showed the strongest association with shortterm mortality and they represented the items of the proposed risk score, whose cut-off of 3 points is able to discriminate patients at higher risk of mortality. AHF represents one of the major challenges in CCU. The use of a combined biochemical and advanced echocardiographic score, assessed at admission, could help to better predict mortality risk, in addition to commonly used indexes.

Anterior chest wall resection and sternal body wedge for primary chest wall tumour: reconstruction technique with biological meshes and titanium plates.

Chest wall tumours are heterogeneous neoplasms, either primary or metastatic, with a malignancy rate of 50%. Surgical resection is one of the mainstays of the treatment, however, chest wall resections can be particularly challenging depending onto the resection size, site and patient habitus. The surgical strategy should be carefully analysed preoperatively, keeping in mind the need of an oncological radical resection (R0) in accordance to the reconstruction principles elicited by le Roux and Sherma since 1983, which include restoring the chest wall rigidity, preserving pulmonary mechanics, protect the intrathoracic organs, avoiding paradox movements of the chest cavity and, possibly, to reduce the thoracic deformity. In this context, we herewith report our surgical reconstruction technique following an anterior chest wall resection and sternal body wedge for a primary chest wall tumour (chondrosarcoma).

Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis.

Based on promising results in preclinical models, clinical trials have been performed to evaluate the efficacy of the first-in-class proteasome inhibitor bortezomib towards malignant pleural mesothelioma (MPM), an aggressive cancer arising from the mesothelium of the serous cavities following exposure to asbestos. Unexpectedly, only minimal therapeutic benefits were observed, thus implicating that MPM harbors inherent resistance mechanisms. Identifying the molecular bases of this primary resistance is crucial to develop novel pharmacologic strategies aimed at increasing the vulnerability of MPM to bortezomib. Therefore, we assessed a panel of four human MPM lines with different sensitivity to bortezomib, for functional proteasome activity and levels of free and polymerized ubiquitin. We found that highly sensitive MPM lines display lower proteasome activity than more bortezomib-resistant clones, suggesting that reduced proteasomal capacity might contribute to the intrinsic susceptibility of mesothelioma cells to proteasome inhibitors-induced apoptosis. Moreover, MPM equipped with fewer active proteasomes accumulated polyubiquitinated proteins, at the expense of free ubiquitin, a condition known as proteasome stress, which lowers the cellular apoptotic threshold and sensitizes mesothelioma cells to bortezomib-induced toxicity as shown herein. Taken together, our data suggest that an unfavorable load-versus-capacity balance represents a critical determinant of primary apoptotic sensitivity to bortezomib in MPM.

Detection of ROS1 rearrangement in non-small cell lung cancer: current and future perspectives.

ROS1 rearrangement characterizes a small subset (1%-2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of ROS1 rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of ROS1 rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner. On the other hand, immunohistochemistry is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all ROS1 fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. This review is a discussion on the present and futuristic diagnostic scenario of ROS1 identification in lung cancer.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results of quality indicators on screen-detected lesions in Italy, 2011-2012.

This annual survey, conducted by the Italian group for mammography screening (GISMa), collects individual data on diagnosis and treatment of about 50% of screen-detected, operated lesions in Italy. The 2011-2012 results show good overall quality and an improving trend over time. A number of critical issues have been identified, including waiting times (which have had a worsening trend over the years) and compliance with the recommendation of not performing frozen section examination on small lesions. Pre-operative diagnosis improved constantly over time, but there is still a large variation between Regions and programmes. For almost 90% of screen-detected invasive cancers a sentinel lymph node (SLN) biopsy was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN dissection for ductal carcinoma in situ, although apparently starting to decline, deserves further investigation. The detailed results have been distributed, among other ways by means of a web-based data-warehouse, to regional and local screening programmes, in order to allow multidisciplinary discussion and identification of the appropriate solutions to any issues documented by the data. The problem of waiting times should be assigned priority. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making monitoring effective in producing quality improvements with shorter waiting times.

[Audit system on quality of breast cancer diagnosis and treatment: results of quality indicators on screen-detected lesions in Italy, 2010]. / Il "progetto SQTM" sulla qualità di diagnosi e terapia entro i programmi di screening in Italia: risultati 2010.

This survey, conducted by the Italian breast screening network (GISMa), collects yearly individual data on diagnosis and treatment on about 50% of all screen-detected, operated lesions in Italy. The 2010 results show good overall quality and an improving trend over time. Critical issues were identified, including waiting times and compliance with the recommendations on not performing frozen section examination on small lesions. Preoperative diagnosis improved constantly over the years, but there is still a large variation between regions and programmes. For almost 90% of screen-detected invasive cancers the sentinel lymph node technique (SLN) was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN for ductal carcinoma in situ deserves further investigation. The detailed results have been distributed, also by means of a web data warehouse, to regional and local screening programmes in order to allow multidisciplinary discussion and identification of the appropriate solutions to any issues documented by the data. It should be assigned priority to the problem of waiting times. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making monitoring effective in producing quality improvements with shorter waiting times.

Audit on quality of breast cancer diagnosis and treatment in Italy, 2008-2009.

This survey, conducted by the Italian breast screening network (GISMa), collects individual data yearly on about 50% of all screen-detected, operated lesions in Italy. The 2008-2009 results show good overall quality of diagnosis and treatment and an improving trend over time. Critical issues were identified, including waiting times and compliance with the recommendations on not performing frozen section examination on small lesions. Pre-operative diagnosis reached the acceptable target, but there is a large variation between regions and programmes. For almost 90% of screen-detected invasive cancers the sentinel lymph node technique (SLN) was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed, also by means of a web-based data warehouse, to regional and local screening programmes in order to allow multidisciplinary discussion and identification of the appropriate solutions to any problem documented by the data. Specialist breast units with adequate case volume and enough resources would provide the best setting for making audits effective in producing quality improvements with shorter waiting times.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results of quality indicators on screen-detected lesions in Italy, 2007.

This survey, conducted by the Italian Breast Screening Network (GISMa), collects individual data yearly on about 50% of all screen-detected, operated lesions in Italy. The 2007 results show good overall quality of diagnosis and treatment and an improving trend over time. Critical issues were identified concerning waiting times, compliance with the recommendations on not performing frozen section examination on small lesions and on performing specimen X-rays. Preoperative diagnosis reached the acceptable target, but there is a large variation between Regions and programmes. For more than 80%of screen-detected invasive cancers the sentinel lymph node technique (SLN) was performed on the axilla, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed, also by means of a web data-warehouse, to regional and local screening programmes in order to allow multidisciplinary discussion and identification of the appropriate solutions to any problem documented by the data. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making audits effective in producing quality improvements with a shorter waiting times.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results of quality indicators on screen-detected lesions in Italy for 2006 and preliminary results for 2007.

Within this survey, conducted by the Italian Breast Screening Network (Gruppo Italiano per lo Screening Mammografico, GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2006, results showed overall good diagnosis and treatment quality and an improving trend over time. Critical issues were identified in waiting times, compliance with recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis reached the acceptable target, but there is a large variation between Regions and programmes. The sentinel lymph node technique (SLN) was performed on the axilla in more than 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN in ductal carcinoma in situ deserves further investigation. The detailed results have been distributed to regional and local screening programmes, also by means of an online database, in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making audit effective in producing quality improvement with a shortening of waiting times.

Audit system on quality of breast cancer diagnosis and treatment (QT): results of quality indicators on screen-detected lesions in Italy in 2005 and preliminary results for 2006.

Within this survey, conducted by the Italian Group of Mammography Screening (GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2005, results showed overall good diagnosis and treatment quality, and an improving trend over time. Critical issues were identified in waiting times, compliance with the recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis has reached the acceptable target, but room for improvement still exists. The sentinel lymph node technique (SLN) was performed on the axilla in more than 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

Impact of hemorheological and endothelial factors on microcirculation.

Previous studies showed that endothelial alterations caused by physical stress worsened the hemorheological parameters mainly in patients affected by ischemic vascular diseases: major vascular alterations have been found in patients with very high endothelial dysfunction indexes: these indexes are given by the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, an endogenous vasodilator whose synthesis is catalyzed by NOs, can be determined by the Citrulline/Arginine ratio, which represents the level of activity of the enzyme. A very good index of the endothelial dysfunction is asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOs; in fact several studies have demonstrated a strong relationship between ischemic vascular disease and high levels of plasmatic ADMA. Our recent studies on heart failure and on ischemic cerebrovascular diseases evaluate endothelial dysfunctions and hemorheological parameters.

Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study.

BACKGROUND: Animal studies have demonstrated that administration of sildenafil can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oral sildenafil (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits (P=NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9+/-1.1%; after IR: 1.2+/-0.7%, P<0.01). Importantly, sildenafil limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0+/-0.9%; after IR: 6.2+/-1.1%, P=NS; P<0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 10.3+/-1.5%; after IR: 1.3+/-1.4%, P<0.05). CONCLUSIONS: In humans, oral sildenafil induces potent protection against IR-induced endothelial dysfunction through opening of K(ATP) channels. Further studies are needed to test the potential clinical implications of this finding.