Evaluation of “Caterina assay”: An Alternative Tool to the Commercialized Kits Used for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Identification

Abstract: Here we describe the first molecular test developed in the early stage of the pandemic to diagnose the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sardinian patients in February–March 2020, when diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The “Caterina assay” is a SYBR®Green real-time reverse-transcription polymerase chain reaction (rRT-PCR), designed to detect the nucleocapsid phosphoprotein (N) gene that exhibits high discriminative variation RNA sequence among bat and human coronaviruses. The molecular method was applied to detect SARS-CoV-2 in nasal swabs collected from 2110 suspected cases. The study article describes the first molecular test developed in the early stage of the declared pandemic to identify the coronavirus disease 2019 (COVID-19) in Sardinian patients in February–March 2020, when a diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The assay presented high specificity and sensitivity (with a detection limit ≥50 viral genomes/µL). No false-positives were detected, as confirmed by the comparison with two certified commercial kits. Although other validated molecular methods are currently in use, the Caterina assay still represents a valid and low-cost detection procedure that could be applied in countries with limited economic resource

Results from CHIPIX-FE0, a Small Scale Prototype of a New Generation Pixel Readout ASIC in 65nm CMOS for HL-LHC

CHIPIX65-FE0 is a readout ASIC in CMOS 65nm designed by the CHIPIX65 project for a pixel detector at the HL-LHC, consisting of a matrix of 64x64 pixels of dimension 50x50 μm2. It is fully functional, can work at low thresholds down to 250e− and satisfies all the specifications. Results confirm low-noise, fast performance of both the synchronous and asynchronous front-end in a complex digital chip. CHIPIX65-FE0 has been irradiated up to 600 Mrad and is only marginally affected on analog performance. Further irradiation to 1 Grad will be performed. Bump bonding to silicon sensors is now on going and detailed measurements will be presented. The HL-LHC accelerator will constitute a new frontier for particle physics after year 2024. One major experimental challenge resides in the inner tracking detectors, measuring particle position: here the dimension of the sensitive area (pixel) has to be scaled down with respect to LHC detectors. This paper describes the results obtained by CHIPIX65-FE0, a readout ASIC in CMOS 65nm designed by the CHIPIX65 project as small-scale demonstrator for a pixel detector at the HL-LHC. It consists of a matrix of 64x64 pixels of dimension 50x50 um2 pixels and contains several pieces that are included in RD53A, a large scale ASIC designed by the RD53 Collaboration: two out of three front-ends (a synchronous and an asynchronous architecture); several building blocks; a (4x4) pixel region digital architecture with central local buffer storage, complying with a 3 GHz/cm2 hit rate and a 1 MHz trigger rate maintaining a very high efficiency (above 99%). The chip is 100% functional, either running in triggered or trigger-less mode. All building-blocks (DAC, ADC, Band Gap, SER, sLVS-TX/RX) and very front ends are working as expected. Analog performance shows a remarkably low ENC of 90e-, a fast-rise time below 25ns and low-power consumption (about 4μA/pixel) in both synchronous and asynchronous front-ends; a very linear behavior of CSA and discriminator. No significant cross talk from digital electronics has been measured, achieving a low threshold of 250e-. Signal digitization is obtained with a 5b-Time over Threshold technique and is shown to be fairly linear, working well either at 80 MHz or with higher frequencies of 300 MHz obtained with a tunable local oscillator. Irradiation results up to 600 Mrad at low temperature (-20°C) show that the chip is still fully functional and analog performance is only marginally degraded. Further irradiation will be performed up to 1 Grad either at low or room temperature, to further understand the level of radiation hardness of CHIPIX65-FE0. We are now in the process of bump bonding CHIPIX65-FE0 to 3D and possibly planar silicon sensors during spring. Detailed results will be presented in the conference paper

First Measurements of a Prototype of a New Generation Pixel Readout ASIC in 65 nm CMOS for Extreme Rate HEP Detectors at HL-LHC

A first prototype of a readout ASIC in CMOS 65nm for a pixel detector at High Luminosity LHC is described. The pixel cell area is 50x50 um2 and the matrix consists of 64x64 pixels. The chip was designed to guarantee high efficiency at extreme data rates for very low signals and with low power consumption. Two different analogue front-end designs, one synchronous and one asynchronous, were implemented, both occupying an area of 35x35 um2. ENC value is below 100e- for an input capacitance of 50 fF and in-time threshold below 1000e-. Leakage current compensation up to 50 nA with power consumption below 5 uW. A ToT technique is used to perform charge digitization with 5-bit precision using either a 40 MHz clock or a local Fast Oscillator up to 800 MHz. Internal 10-bit DAC's are used for biasing, while monitoring is provided by a 12-bit ADC. A novel digital architecture has been developed to ensure above 99.5% hit efficiency at pixel hit rates up to 3 GHz/cm2, trigger rates up to 1 MHz and trigger latency of 12.5 us. The total power consumption per pixel is below 5uW. Analogue dead-time is below 1%. Data are sent via a serializer connected to a CMOS-to-SLVS transmitter working at 320 MHz. All IP-blocks and front-ends used are silicon-proven and tested after exposure to ionizing radiation levels of 500-800 Mrad. The chip was designed as part of the Italian INFN CHIPIX65 project and in close synergy with the international CERN RD53 and was submitted in July 2016 for production. Early test results for both front-ends regarding minimum threshold, auto-zeroing and low-noise performance are high encouraging and will be presented in this paper

Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications

Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnosesparticularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD

Pontine tegmental cap dysplasia: developmental and cognitive outcome in three adolescent patients

Pontine Tegmental Cap Dysplasia (PTCD) is a recently described, rare disorder characterized by a peculiar cerebellar and brainstem malformation. Nineteen patients have been reported to date, of which only one in the adolescent age, and data on the clinical, cognitive and behavioural outcome of this syndrome are scarce

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Studio di possibili effetti sistematici nelle nuvole di punti SfM da APR: confronti con TLS, distorsioni e metodi di mitigazione

La fotogrammetria Structure-from-Motion (SfM) si basa su algoritmi che permettono, in modo automatico e rapido, di individuare una quantità elevata di punti omologhi tra le immagini acquisite durante il rilievo. L’individuazione di tali punti consente di realizzare l’allineamento delle immagini e quindi la calibrazione esterna ed interna delle fotocamere. L’efficienza di tali algoritmi e la quantità, qualità e distribuzione spaziale dei punti omologhi sono il fulcro della procedura di restituzione fotogrammetrica. In alcuni casi, per una combinazione tra strategia di acquisizione, tipo di fotocamera e software utilizzato, potrebbero verificarsi delle anomalie che danno luogo a distorsioni delle nuvole di punti finali. Il lavoro presenta i rilievi SfM realizzati nell’ambito di un progetto per lo studio delle deformazioni dovute al fenomeno della liquefazione mediante il confronto di modelli multi­temporali; si tratta dell’unico caso da noi osservato in anni di esperienza di rilievo SfM in cui sono presenti effetti sistematici che hanno reso problematico l’uso diretto delle nuvole di punti ottenute utilizzando Photoscan. Si mostrano i tentativi per ridurre tali effetti sia mediante un sotto­campionamento delle immagini, al fine di equilibrare la distribuzione dei punti omologhi, sia inibendo l’aggiustamento dei parametri interni, fino ad ottenere risultati utilizzabili, seppur non completamente liberi da sistematismi. Nella valutazione dei problemi è stato utilizzato un rilievo di riferimento realizzato mediante Terrestrial Laser Scanning (TLS). Infine tutti i dati sono stati rielaborati con un software migliorato, Metashape, ottenendo risultati non affetti da sistematismi, il che indica che le procedure per l’individuazione dei punti omologhi sono state migliorate. Poiché Photoscan (nelle versioni ancora utilizzate dalla 1.2 alla 1.7) è un prodotto molto diffuso, si ritiene che questa esperienza possa essere utile a quanti sono coinvolti in attività di monitoraggio e studio delle deformazioni superficiali. Structure from Motion (SfM) photogrammetry is based on the use of algorithms allowing the automatically identification of a large amount of homologous points (or pixels) between images overlapping areas. The coordinates of the homologous points (provided in different reference systems for each acquisition), allow the images alignment meaning the internal and external camera calibration. The number and the distribution of homologous points drives the entire procedure of photogrammetric restitution. In some cases, due to a fatal combination of acquisition strategy, digital cameras and software, anomalies could occur causing systematic effects in the point clouds representing the observed surfaces. This paper shows the results obtained from SfM surveys carried out as part of a project for the study of deformations due to the phenomenon of liquefaction by comparing multi-temporal models. This is the only case we have observed in years of SfM survey experience in which there are systematic effects preventing the direct use of the point clouds obtained using Photoscan (versions 1.1.2 and 1.7.0). Some approaches aimed at mitigating the distortions by balancing the distribution of homologous points and inhibiting the adjustment of internal camera calibration are used to improve results. A reference Terrestrial Laser Scanning (TLS) survey allowed the evaluation unexpected problems. Finally, the images data set processed by means of Metashape (1.5.0), a new improved version of Photoscan, provide good results free from systematism proving the greater efficiency of new algorithms for homologous points selection optimization. Since Photoscan is a very widespread product and also used within the INGV, it is believed that this experience can be useful to many operators involved in monitoring and studying surface deformations