Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Hybrid MPPT method based on Neural Network and Perturb & Observe for PV systems

To track accurately and fast the Maximum Power Point (MPP), a hybrid technique NN-P&amp;O switched between Neural Network (NN) and Perturb and Observe method (P&amp;O) according to the variation of irradiation was proposed. The considered methodology is based on voltage reference estimated by NN and achieved using proportional-integral controller (PI). The error between the actual power and the optimal power was minimized using a small duty cycle steps generated by P&amp;O method, which initial duty cycle value was updated adaptively. To approve the efficiency of the proposed control algorithms, simulations have been performed considering different system responses as the current, voltage and essentially the power under changing weather conditions (irradiance or temperature values).</p

How to assess ankle osteoarthritis: comparison of the Kellgren and Lawrence scale with functional outcome and digital image analysis

Introduction Currently, a validate scale of ankle osteoarthritis (OA) is not available and different classifications have been used, making comparisons between studies difficult. In other joints as the hip and knee, the Kellgren-Lawrence (K&L) scale, chosen as reference by the World Health Organizations is widely used to characterize OA. It consists of a physician based assessment of 3 radiological features: osteophyte formation, joint space narrowing and bone end sclerosis described as follows: grade 0: normal joint; grade 1: minute osteophytes of doubtfull significance; grade 2: definite osteophytes; grade 3: moderate diminution of joint space; grade 4: joint space greatly impaired, subchondral sclerosis. Until now, the K&L scale has never been validated in the ankle. Our objective was to assess the usefulness of the K&L scale for the ankle joint, by determining its reliability and by comparing it to functional scores and to computerized minimal joint space width (minJSW) and sclerosis measurements. Additionally we propose an atlas of standardized radiographs for each of the K&L grades in the ankle. Methods 73 patients 10 to 20 years post ankle ORIF were examined. Bilateral ankle radiographs were taken. Four physicians independently assessed the K&L grades and evaluated tibial and talar sclerosis on anteroposterior radiographs. Functional outcome was assessed with the AOFAS Hindfoot score. Bone density and minJSW were measured using a previously validated Ankle Image Digital Analysis software (AIDA). Results The interobserver reliability, for the K&L stages was 0.60 (intraclass correlation coefficient) indicating moderate to good agreement. The mean AOFAS hindfoot score decreased substantially (p = 009) and linearly from 99.3 in K&L grade 0 to 79.5 points in K&L grade 4. The minJSW assessed by AIDA was similar among grades 0 to 2 (between 2 and 2.5mm), but significantly lower in grade 3 (1.8mm) and in grade 4 (1.1mm). A decreased minJSW less than 2mm, commonly used as a threshold for the assessment of hip and knee OA, was found in 77% of K&L grades 3–4 compared to 33% of grades 0–2, sensitivity 77.4% and specificity 66.7%. Physician based assessment revealed that subchondral sclerosis was present in 16% of K&L grade 1 patients, 52% of grade 2, 70% of grade 3 and 100% of grade 4 patients. No correlation could be found between physician based assessment and digital image analysis of subchondral sclerosis. Conclusions Interobserver reliability in assessment of ankle OA using the K&L scale was similar to other previously described joints. OA progression correlated with functional diminution. Joint space narrowing assessed AIDA as well as the cut-off of 2mm correlated well with the K&L scale. Overall, we recommend the use of the K&L scale for the radiographic assessment of ankle OA

Primary small-cell neuroendocrine carcinoma of the bladder: case report and literature review

Background: Neuroendocrine tumours (NET) are extremely rare and aggressive. Although they commonly affect intestine, many organs may be involved such as pancreas, lung or urinary tract. Bladder is rarely involved. Actually, two main forms of bladder NET have been described: small-cell and large-cell. The first one is considered highly agressive since it shows poor oncologic outcomes being mainly diagnosed at advanced stage: the second one is extremely rare and equally aggressive. Case report: A 78-years-old Caucasian male presented to our facility for lower urinary tract symptoms and gross hematuria recently occurred. He was a strong smoker since many years. No familiarity for urothelial cancer was referred nor previous episodes of hematuria until that time. Citology was negative; outpatient ultrasound of the bladder revealed a 3 cm bladder thickening highly suspicious for bladder cancer; patient underwent TC scan that confirmed the bladder lesion. A transurethral resection of the bladder (TURB) was performed. After 3 months total body TC showed multiple visceral metastases also involving brain and lymph nodes. Best supportive care was offered but the patient died 6 months later. Results: Pathology revealed a mixed bladder tumor: 30% of the specimen resulted as an high-grade urothelial cancer (G3) and 70% as small-cell neuroendocrine variant.Microscopic muscle involvement was excluded. Conclusions: Neuroendocrine tumors are uncommon entities which origin from cells of neuro-endocrine system and may potentially involve all human tissues. Neuroendocrine smallcell carcinoma of the bladder is a non-urothelial histotype: it is highly aggressive and diagnosed mainly at advanced stages. Whenever considering the high risk of metastatic spread and the poor prognosis, a multimodal approach is highly suggested. TURB alone is uneffective in disease control due to its aggressive nature. Unless metastatic, radical cystectomy and adjuvant chemotherapy represent the gold standard

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA

Sensitivity of the Cherenkov Telescope Array to the gamma-ray emission from neutrino sources detected by IceCube

Gamma-ray observations of the astrophysical neutrino sources are fundamentally important for understanding the underlying neutrino production mechanism. We investigate the Cherenkov Telescope Array (CTA) ability to detect the very-high-energy (VHE) gamma-ray counterparts to the neutrino-emitting Active Galaxies. The CTA performance under different configurations and array layouts is computed based on the neutrino and gamma-ray simulations of steady and transient types of sources, assuming that the neutrino events are detected with the IceCube neutrino telescope. The CTA detection probability is calculated for both CTA sites taking into account the visibility constraints. We find that, under optimal observing conditions, CTA could observe the VHE gamma-ray emission from at least 3 neutrino events per year

Performance of a proposed event-type based analysis for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) will be the next-generation observatory in the field of very-high-energy (20 GeV to 300 TeV) gamma-ray astroparticle physics. Classically, data analysis in the field maximizes sensitivity by applying quality cuts on the data acquired. These cuts, optimized using Monte Carlo simulations, select higher quality events from the initial dataset. Subsequent steps of the analysis typically use the surviving events to calculate one set of instrument response functions (IRFs). An alternative approach is the use of event types, as implemented in experiments such as the Fermi-LAT. In this approach, events are divided into sub-samples based on their reconstruction quality, and a set of IRFs is calculated for each sub-sample. The sub-samples are then combined in a joint analysis, treating them as independent observations. This leads to an improvement in performance parameters such as sensitivity, angular and energy resolution. Data loss is reduced since lower quality events are included in the analysis as well, rather than discarded. In this study, machine learning methods will be used to classify events according to their expected angular reconstruction quality. We will report the impact on CTA high-level performance when applying such an event-type classification, compared to the classical procedure

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA