Routine blood analysis greatly reduces the false-negative rate of RT-PCR testing for COVID-19

Background: The COVID-19 outbreak is now a pandemic disease reaching as much as 210 countries worldwide with more than 2.5 million infected people and nearly 200.000 deaths. Amplification of viral RNA by RT-PCR represents the gold standard for confirmation of infection, yet it showed false-negative rates as large as 15-20% which may jeopardize the effect of the restrictive measures taken by governments. We previously showed that several hematological parameters were significantly different between COVID-19 positive and negative patients. Among them aspartate aminotransferase and lactate dehydrogenase had pre-dictive values as large as 90%. Thus a combination of RT-PCR and blood tests could reduce the false-negative rate of the genetic test. Methods: We retrospectively analyzed 24 patients showing multiple and inconsistent RT-PCR, test during their first hospitalization period, and compared the genetic tests results with their AST and LDH levels. Results: We showed that when considering the hematological parameters, the RT-PCR false-negative rates were reduced by almost 4-fold. Conclusions: The study represents a preliminary work aiming at the development of strategies that, by combining RT-PCR tests with routine blood tests, will lower or even abolish the rate of RT-PCR false-negative results and thus will identify, with high accuracy, patients infected by COVID-19. (www.actabiomedica.it)

Development, evaluation, and validation of machine learning models for COVID-19 detection based on routine blood tests

The rRT-PCR test, the current gold standard for the detection of coronavirus disease (COVID-19), presents with known shortcomings, such as long turnaround time, potential shortage of reagents, false-negative rates around 15-20%, and expensive equipment. The hematochemical values of routine blood exams could represent a faster and less expensive alternative. Three different training data set of hematochemical values from 1,624 patients (52% COVID-19 positive), admitted at San Raphael Hospital (OSR) from February to May 2020, were used for developing machine learning (ML) models: the complete OSR dataset (72 features: complete blood count (CBC), biochemical, coagulation, hemogasanalysis and CO-Oxymetry values, age, sex and specific symptoms at triage) and two sub-datasets (COVID-specific and CBC dataset, 32 and 21 features respectively). 58 cases (50% COVID-19 positive) from another hospital, and 54 negative patients collected in 2018 at OSR, were used for internal-external and external validation. We developed five ML models: for the complete OSR dataset, the area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.83 to 0.90; for the COVID-specific dataset from 0.83 to 0.87; and for the CBC dataset from 0.74 to 0.86. The validations also achieved good results: respectively, AUC from 0.75 to 0.78; and specificity from 0.92 to 0.96. ML can be applied to blood tests as both an adjunct and alternative method to rRT-PCR for the fast and cost-effective identification of COVID-19-positive patients. This is especially useful in developing countries, or in countries facing an increase in contagions

Hazard-consistent response spectra in the Region of Murcia (Southeast Spain): comparison to earthquake-resistant provisions

Hazard-consistent ground-motion characterisations of three representative sites located in the Region of Murcia (southeast Spain) are presented. This is the area where the last three damaging events in Spain occurred and there is a significant amount of data for comparing them with seismic hazard estimates and earthquake-resistant provisions. Results of a probabilistic seismic hazard analysis are used to derive uniform hazard spectra (UHS) for the 475-year return period, on rock and soil conditions. Hazard deaggregation shows that the largest hazard contributions are due to small, local events for short-period target motions and to moderate, more distant events for long-period target motions. For each target motion and site considered, the associated specific response spectra (SRS) are obtained. It is shown that the combination of two SRS, for short- and long-period ground motions respectively, provides a good approximation to the UHS at each site. The UHS are compared to design response spectra contained in current Spanish and European seismic codes for the 475-year return period. For the three sites analysed, only the Eurocode 8 (EC8) type 2 spectrum captures the basic shape of the UHS (and not the EC8 type 1, as could be expected a priori). An alternative response spectrum, anchored at short- and long-period accelerations, is tested, providing a close match to the UHS spectra at the three sites. Results underline the important contribution of the frequent, low-to-moderate earthquakes that characterize the seismicity of this area to seismic hazard (at the 475-year return period)

Counteracting effects operating on Src homology 2 domain-containing protein-tyrosine phosphatase 2 (SHP2) function drive selection of the recurrent Y62D and Y63C substitutions in Noonan syndrome

Activating mutations in PTPN11 cause Noonan syndrome, the most common nonchromosomal disorder affecting development and growth. PTPN11 encodes SHP2, an Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase that positively modulates RAS function. Here, we characterized functionally all possible amino acid substitutions arising from single-base changes affecting codons 62 and 63 to explore the molecular mechanisms lying behind the largely invariant occurrence of the Y62D and Y63C substitutions recurring in Noonan syndrome. We provide structural and biochemical data indicating that the autoinhibitory interaction between the N-SH2 and protein-tyrosine phosphatase (PTP) domains is perturbed in both mutants as a result of an extensive structural rearrangement of the N-SH2 domain. Most mutations affecting Tyr(63) exerted an unpredicted disrupting effect on the structure of the N-SH2 phosphopeptide-binding cleft mediating the interaction of SHP2 with signaling partners. Among all the amino acid changes affecting that codon, the disease-causing mutation was the only substitution that perturbed the stability of the inactive conformation of SHP2 without severely impairing proper phosphopeptide binding of N-SH2. On the other hand, the disruptive effect of the Y62D change on the autoinhibited conformation of the protein was balanced, in part, by less efficient binding properties of the mutant. Overall, our data demonstrate that the selection-by-function mechanism acting as driving force for PTPN11 mutations affecting codons 62 and 63 implies balancing of counteracting effects operating on the allosteric control of the function of SHP2

Recorded Motions of the Mw6.3 April 6, 2009 L’Aquila (Italy) Earthquake and Implications for Building Structural Damage: Overview.

The normal-faulting earthquake of 6 April 2009 in the Abruzzo Region of central Italy caused heavy losses of life and substantial damage to centuriesold buildings of significant cultural importance and to modern reinforcedconcrete- framed buildings with hollow masonry infill walls. Although structural deficiencies were significant and widespread, the study of the characteristics of strong motion data from the heavily affected area indicated that the short duration of strong shaking may have spared many more damaged buildings from collapsing. It is recognized that, with this caveat of shortduration shaking, the infill walls may have played a very important role in preventing further deterioration or collapse of many buildings. It is concluded that better new or retrofit construction practices that include reinforcedconcrete shear walls may prove helpful in reducing risks in such seismic areas of Italy, other Mediterranean countries, and even in United States, where there are large inventories of deficient structures.Published651-6844.1. Metodologie sismologiche per l'ingegneria sismicaJCR Journalreserve

Similarity Patterns and Stability of Environmental Response in Sunflower Hybrids

The rationale for the following research was to analyse the response of sunflower hybrids to different sowing dates and to evaluate hybrid response to critical environmental conditions. The data used are from an experiment conducted in a location-year combination over a period of two years (2007-09) in southern Italy. Eleven hybrids were tested following a randomized complete block design with three replications at each location-year combination. Eight agronomic characters including seed oil content were recorded. Classification and ordination procedures were used to investigate hybrid performance in relation to three different sowing dates. Combined analysis of variance showed that hybrids, location-year combination, sowing date and their interactions were highly significant for all characters. Hybrid performances were classified by cluster analysis into groups that were differentiable in terms of means and stability. The first three components accounted for 74%, 82%, and 87% of the total variation for the first, second and third sowing date respectively. Plotting component one against component two along Euclidean axes should therefore provide a reasonable representation of the spatial arrangements of hybrid performances in the original multi-dimensional space. The applied statistical method gives full information on hybrid performances similarity