32 × 32 CMOS SPAD Imager for Gated Imaging, Photon Timing, and Photon Coincidence

We present the design and simulations of a single-photon sensitive imager based on single photon avalanche diodes (SPADs) with an innovative pixel architecture that includes four separate SPADs with independent active time-gating and quenching circuit, a shared time-to-digital converter (TDC) with 50-ps resolution, four independent photon counters, and multiple operation modes. The TDC is driven by smart arbitration logic, which preserves spatial information among the four detectors; furthermore, an alternative operation mode exploits photon-coincidence on multiple detectors to reduce the effect of high background levels, e.g., in light detection and ranging applications with strong ambient light. Key features are the ability to operate in simultaneous photon counting and timing modes for capturing 2-D and 3-D images of the scene in a single shot (frame), the option of a counting-only mode, reducing power consumption, and increasing achievable frame-rate when timing information is not needed, and the ability to individually shut down noisy detectors or to enable just some regions of interests

A Risk Assessment for Road Transportation of Dangerous Goods: A Routing Solution☆

Abstract Improve road traffic safety is one of the most important objectives for transport policy makers in contemporary society, and represents a strategic issue for enhance life quality. Recently ISO 39001 (Road Traffic Safety Management Systems) introduced the guidelines of safety-based activities aimed to decreasing road accidents, in agreement with the Quality Management Systems (ISO 9000). Such guidelines are intended for infrastructure managers, administrators, and private entities, and defines a standard management for reduction of road risk. In this context, the risk arising by dangerous goods transport represents a particular threat which needs strategies and tools to reduce risk rate of society, property and environment. Several decision making solutions for transport managers and public administration are defined, but two open points still exist. Firstly, there are not applications supporting for dangerous goods carriers in tactical and operational planning. The second point is related to impacts of traffic congestion on road accidents frequency: there is not a common approach for study and assessment these relationships. The aim of this paper is to analyze the interactions between road traffic flow and frequency of accidents: the paper propose an integrated approach for the study of routing problems considering safety. The first part concerns a brief critical review on literature solutions. Following is presented a new approach to analyze a road accident involving a dangerous goods, focusing on the reason which lead to a leakage of hazardous materials. This paper presents an upgrade of a minimum cost routing problem for a road carrier considering also the risk related to dangerous goods. After a description on how computing risk concerning dangerous goods transportation in a routing choice problem, the paper describes a solution aimed at providing a tactical and operating decision-making tool. The aim is to enable the carrier that transport dangerous goods to calculate the quantification of the risk for each specific trip in addition to operating cost for each specific transport. The added value of risk quantification could be used by transportation carrier in ISO 39001 to numerically prove his own safety-decisions to the control authority. The analysis developed has provided good results. The approach defined, albeit simplified, is a useful tool, especially when ISO 39001 standards will strengthen road safety

Gated SPAD Arrays for Single-Photon Time-Resolved Imaging and Spectroscopy

In this paper, we present the architecture and the experimental characterization of an improved version of a previously developed 32 × 32 Single Photon Avalanche Diodes (SPADs) and Time to Digital Converters (TDCs) array, and two new arrays (with 8 × 8 and 128 × 1 pixels) with the additional capability of actively gating the detectors with sub-nanosecond rise time. The arrays include high performance SPADs (0.04 cps/μm2, 50% peak PDE) and provide down to 410 ps Full-Width at Half-Maximum (FWHM) single shot precision and excellent linearity. We developed a camera to exploit these imagers in time-resolved, single-photon applications

Spatial images from temporal data

Traditional paradigms for imaging rely on the use of a spatial structure, either in the detector (pixels arrays) or in the illumination (patterned light). Removal of the spatial structure in the detector or illumination, i.e., imaging with just a single-point sensor, would require solving a very strongly ill-posed inverse retrieval problem that to date has not been solved. Here, we demonstrate a data-driven approach in which full 3D information is obtained with just a single-point, single-photon avalanche diode that records the arrival time of photons reflected from a scene that is illuminated with short pulses of light. Imaging with single-point time-of-flight (temporal) data opens new routes in terms of speed, size, and functionality. As an example, we show how the training based on an optical time-of-flight camera enables a compact radio-frequency impulse radio detection and ranging transceiver to provide 3D images.Comment: This is the final version as published in Optica Vol. 7, Issue 8, pp. 900-905 (2020

Clinical outcomes and safety of patients treated with NAb-Paclitaxel plus Gemcitabine in metastatic pancreatic cancer:the NAPA study

BACKGROUND: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice.METHODS: From January 2015 to December 2018, patients with metastatic PDAC receiving first-line treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed.RESULTS: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95 % CI; 9-13) and the median progression free survival (PFS) was 6 months (95 % CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 haematological toxicity frequency was 22.61% for neutropenia, 5.22% for anaemia and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 nonhaematological events were reported. Dose reduction was necessary in 51.3 % of the patients.CONCLUSIONS: Our results confirm the efficacy and safety of a first line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.</p

Smart Optode for 8-Wavelength Time-Gated Diffuse Optics

We present the most compact (4 cm3) time domain diffuse optical spectroscopy system, hosting 8 laser sources emitting at different wavelengths, a large area time-gated detector, and a time-to-digital converter. We tested the optode using standardized protocols, enlightening a high light harvesting capability and large penetration depth in detecting realistic optical inhomogeneities. We tested it also in vivo for the non-invasive assessment of blood parameters in a vascular occlusion test and for the detection of brain activation, demonstrating the optode capability to follow task-related hemodynamic changes even through a single measurement, with no need for averaging or filtering as instead needed with most available systems. The optode is thus a good candidate for next generation home-monitoring devices, thanks to its good performances, small dimension and potential low-cost

Prognostic value of normal sodium levels in patients with metastatic renal cell carcinoma receiving tyrosine kinase inhibitors

Background: Although serum sodium concentration, particularly hyponatremia, has been shown to be a prognostic marker of survival in metastatic renal cell carcinoma (mRCC), the impact of normal sodium levels has not been investigated. Herein, we investigate the influence of normonatremia in mRCC patients treated with tyrosine kinase inhibitors (TKIs). Materials and methods: For this retrospective study, the clinical and biochemical data of patients treated with first-line TKIs for mRCC were available from seven Italian cancer centers. We collected natremia levels at baseline and first evaluation after treatment excluding patients with sodium levels outside the normal range (&lt;135 or &gt;145 mEq/L). The remaining patients were subdivided into two groups according to the median sodium value: natremia patients with &lt;140 mEq/L (n = 132) and baseline natremia patients with ≥140 mEq/L (n = 185). Subsequently, we analyzed the impact of sodium levels on response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). PFS and OS were estimated through the Kaplan–Meier method, and differences between groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were applied to evaluate the prognostic factors for PFS and OS. Results: Of the 368 patients, 317 were included in the analysis, 73.1% were men, and the median age was 67 years (range 36–89). When comparing patients with baseline natremia ≥140 mEq/L (n = 185) to patients with natremia &lt;140 mEq/L (n = 132), the PFS was 15 vs. 10 months (p &lt; 0.01) and the OS was 63 vs. 36 months, respectively (p = 0.02). On the first evaluation, patients with serum sodium ≥140 mEq/L had longer PFS (15 vs. 10 months, p &lt; 0.01) and OS (70 vs. 32 months, p &lt; 0.01) than patients with levels &lt;140 mEq/L. Moreover, clinical outcomes showed a significant improvement in patients with natremia ≥140 mEq/L compared with patients with levels &lt;140 mEq/L both at baseline and first evaluation: PFS was 19 vs. 11 months (p &lt; 0.01) and OS was 70 vs. 36 months (p &lt; 0.01), respectively. Conclusions: To the best of our knowledge, this is the first study to investigate the impact of normonatremia in mRCC. We found that serum sodium levels &lt;140 mEq/L at baseline and first assessment are independently associated with worse PFS and OS in mRCC patients treated with TKIs in the first-line setting

The SOLUS instrument: Optical characterization of the first hand-held probe for multimodal imaging (ultrasound and multi-wavelength time-resolved diffuse optical tomography)

SOLUS is a multimodal imaging system comprising the first miniaturized handheld device to perform time domain Diffuse Optical Tomography at 8 visible and near infrared wavelengths. The hand-held probe also includes B-mode ultrasounds, Shear Wave Elastography and Color Doppler sonography, being its first goal the multiparametric non-invasive diagnosis of breast cancer. This work aims at presenting the system and its main capabilities, focusing on the optical characterization carried out to assess the overall performance of the developed photonics technologies (picosecond pulsed lasers, high-sensitive time-gated sensors and integrated electronics) and of the software for tomographic reconstructions (perturbative model based on Born approximation). Systematic measurements performed on tissue-mimicking phantoms, reproducing a perturbation (e.g., a lesion) in a homogenous background, helped understand the system efficiency range. Variations in absorption are tracked with acceptable quality, which is key to estimate tissue composition, up to 0.25 cm 1 for the bulk (relative error on average of 16 %) and 0.16 cm 1 for sufficiently big perturbations (relative error on average of 26 % for 6 cm3 inhomogeneities). Instead, the system showed low sensitivity to a localized perturbation in scattering and a relative error on average of 17 % for the scattering bulk assessment. An example case of clinical measurement is also discussed