Inappropriateness in laboratory medicine: An elephant in the room?

Appropriateness of diagnostic testing can be conventionally described as prescription of the right test, using the right method, at the right time, to the right patient, with the right costs and for producing the right outcome. There is ongoing debate about the real burden of inappropriateness in laboratory diagnostics. The media coverage of this issue has also recently led to either over- or under-emphasizing the clinical, organizational and economic consequences. This is quite problematic, inasmuch as some reliable data are available in the current scientific literature, showing that inappropriateness of laboratory testing can be as high as 70%. This is especially evident for, though not limited to, cancer biomarkers testing, in which the practice of avoidable tests ordering is dramatically magnified. The reasons beyond inappropriateness are many and multifaceted, entailing wrong habits, resistance to changes, poor culture, insufficient education and healthcare inefficiencies. There are many unfavorable consequences attributable to avoidable testing, including unjustified incremental costs, derangement of laboratory efficiency and potential patient safety issues. The tentative solutions to this important problem necessitate that policymakers, local hospital administrators, laboratory professionals, clinicians, patients' associations and diagnostic companies join the efforts and embark in the same landmark effort for disseminating a better culture of appropriateness

Seismic images of an extensional basin, generated at the hangingwall of a low-angle normal fault: the case of the Sansepolcro basin (Central Italy)

The study of syntectonic basins, generated at the hanging-wall of regional low-angle detachments, can help to gain a better knowledge of these important and mechanically controversial extensional structures, constraining their kinematics and timing of activity. Seismic reflection images constrain the geometry and internal structure of the Sansepolcro Basin (the northernmost portion of the High Tiber Valley). This basin was generated at the hangingwall of the Altotiberina Fault (AtF), an E-dipping low-angle normal fault, active at least since Late Pliocene, affecting the upper crust of this portion of the Northern Apennines. The dataset analysed consists of 5 seismic reflection lines acquired in the 80s’ by ENI-Agip for oil exploration and a portion of the NVR deep CROP03 profile. The interpretation of the seismic profiles provides a 3-D reconstruction of the basin’s shape and of the sedimentary succession infilling the basin. This consisting of up to 1200 m of fluvial and lacustrine sediments: this succession is much thicker and possibly older than previously hypothesised. The seismic data also image the geometry at depth of the faults driving the basin onset and evolution. The western flank is bordered by a set of E-dipping normal faults, producing the uplifting and tilting of Early to Middle Pleistocene succession along the Anghiari ridge. Along the eastern flank, the sediments are markedly dragged along the SW-dipping Sansepolcro fault. Both NE- and SW-dipping faults splay out from the NE-dipping, low-angle Altotiberina fault. Both AtF and its high-angle splays are still active, as suggested by combined geological and geomorphological evidences: the historical seismicity of the area can be reasonably associated to these faults, however the available data do not constrain a unambiguous association between the single structural elements and the major earthquakes

Application of a new Structural Joint Inversion Approach to Teleseismic and Gravity Data from Mt.Vesuvius, Italy

A 3-D joint inversion of seismic and gravimetric data is performed to re-investigate the subsurface structure of Mt. Vesuvius (Italy) utilizing an improved joint inversion method. The aim is to derive models of the 3D distribution of velocity and density perturbations that are consistent with both data sets and with local velocity models. Mt. Vesuvius is a strato volcano located within a graben (Campania Plain) formed in Plio-Pleistocene. Campania Plain is bordered by mostly Mesozoic carbonaceous rocks. Mt. Vesuvius is the southernmost and the youngest of a group of Pleistocene volcanoes, three of which (Ischia, Campi Flegrei and Mt. Vesuvius) have erupted in historical times. The most recent eruption of Mt. Vesuvius occurred in 1944 and since then the volcanic activity has been characterized by moderate low magnitude seismicity and low temperature fumaroles at the summit crater. We modified the coupling mechanism between velocity and density models in the JI-3D optimized joint inversion method (Jordan and Achauer, 1999). This method was designed to provide stable and high resolution results and involves iterative optimized parameterization, 3D ray tracing, and the incorporation of a priori information. The coupling of the velocity and density models, vital to the joint inversion, is based on a cross-gradient approach (e.g. Gallardo and Meju, 2004), which has been proven to work very well in a variety of cases involving seismic, magnetic, CSEM, MT and gravity data sets. We implemented the cross-gradient coupling for our 3-D irregular adaptive grid parameterization. In contrast to conventional joint inversion methods this approach encourages structural similarities in the models and does not rely on predefined relationships between velocity and density parameters. As a consequence, the resulting velocity-density relations are not contaminated by a priori assumptions and can be utilized to derive rock physical parameters. We apply this method to data from the TomoVes project (Gasparini et al. 1998), combining seismics and Bouguer gravity and local high resolution velocity models as a priori information. The starting models for the joint inversion are derived by separate inversions of the individual data sets. We show 3D distributions of velocity perturbations and density variations from the joint inversion of teleseismic relative traveltimes and Bouguer anomaly data with the aim of extracting further information about the physical status of the volcano- tectonic system

Historical and Instrumental Seismicity of the Sansepolcro Basin, Northern Apennines, Italy

In this work we analyse the most important earthquakes of the 20th century occurred in the Altotiberina Valley in 1917, 1918, 1919 and 1948; in particular instrumental relocation and Ms magnitude estimation are re-evaluated. The area investigated, the Sansepolcro basin, is characterized by the presence of important earthquakes in the past with estimated intensity even larger than IX MCS (the 1352 Monterchi earthquake, the 1389 Boccaserriola, the 1458 Citta' di Castello, the 1781 Cagliese and the 1917 Monterchi-Citerna earthquakes, CPTI Working Group, 2004) and by a surprisingly scarce instrumental seismicity compared to the adjacent areas struck by high seismicity (Castello et al., 2005; Ciaccio et al., 2006). In particular, the area north of Sansepolcro has been struck in recent years by four minor sequences, occurred between 1987 and 2001 with magnitude ranging from Ml3.0 to Mw4.7. The relocation of these earthquakes is particularly critical and in an important issue. An instrumental and precise location is critical for the complexity of the problems associated with the study of seismograms prior to the rst half of the twentieth century and is relevant because in the surrounding regions higher seismicity is observed. Regarding this peculiarity of the area, it’s very important to detect the localization of the historical earthquakes: in particular, the 1917 event is often associated to the possibility that the regional low angle Altotiberina Fault (Barchi et al., 1998) is able or not to nucleate large- or moderate-magnitude events, being historically located close to its surface (Boncio and Lavecchia, 2000)

Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3 . The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants. Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels. Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility

Presence of Candida zemplinina in Sicilian Musts and Selection of a Strain for Wine Mixed Fermentations

The purpose of this work was to investigate the presence of C. zemplinina yeasts in Sicilian musts andgrapes and to identify strains of oenological interest. We report on the taxonomical reclassificationof Candida yeast isolates from Sicilian musts and on the selection of one strain of oenological interest(Cz3), based on mixed micro-fermentation experiments in sterile Nero d’Avola musts. Our results showthat Candida zemplinina is abundant in Sicilian grapes and musts, and that the Cz3 strain is suitablefor Candida zemplinina/Saccharomyces cerevisiae mixed fermentations. The higher glycerol content andthe lower ethanol level stood out as the most promising features of the wines obtained upon sequentialinoculation of the Cz3 and (S. cerevisiae) NDA21 yeast starters. We therefore have isolated a Sicilian Czstrain endowed with very promising features for the future development of mixed fermentation protocols

Evaluation of anti-sars-cov-2 s-rbd igg antibodies after covid-19 mrna bnt162b2 vaccine

(1) Background: The evaluation of anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the individual protection against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection; (2) Methods: We evaluated anti S-RBD IgG levels by indirect chemiluminescence immunoassay on Maglumi 800 (SNIBE, California) in 2248 vaccinated subjects without previous SARS-CoV-2 infection, 91 vaccinated individuals recovered from COVID-19, and 268 individuals recovered from COVID-19 who had not been vaccinated. Among those who were healthy and vaccinated, 352 subjects performed a re-dosing after about 72 days from the first measurement. (3) Results: Anti S-RBD IgG levels were lower in subjects with previous infection than vaccinated subjects, with or without previous infection (p < 0.001). No difference was observed between vaccinated subjects, with and without previous SARS-CoV-2 infection. Overall, anti-RBD IgG levels were higher in females than males (2110 vs. 1341 BAU/mL; p < 0.001) as well as in subjects with symptoms after vaccination than asymptomatic ones (2085 vs. 1332 BAU/mL; p = 0.001) and lower in older than younger subjects. Finally, a significant decrease in anti-RBD IgG levels was observed within a short period from a complete two-dose cycle vaccination. (4) Conclusions: Our results show an efficacy antibody response after vaccination with age-, timeand sex-related differences

A rapid spectroscopic method to detect the fraudulent treatment of tuna fish with carbon monoxide

Carbon monoxide (CO) can be used to treat fresh meat and fish in order to retain its 'fresh' red colour appearance for a longer period of time. In fact, upon aging, myoglobin is oxidized to met-myoglobin with the concomitant blue-shift and broadening of the Soret maximum, which brings about a change in the colour of the fish, revealing that it is no longer fresh. The use of carbon monoxide, which reacts with the oxy-myoglobin to form a fairly stable cherry red carboxy-myoglobin complex may mask spoilage, because the CO-complex can be stable beyond the microbiological shelf life of the meat. The presence of CO in tuna fish has been investigated by optical spectroscopy as the formation of the CO adduct can be easily detected by the combined analysis of electronic absorption spectra in their normal and second derivative modes, monitoring the intense Soret band at 420 nm. The presence of met- and oxy-myoglobin can obscure the presence of small amounts of the CO adduct; however, it can be revealed by chemically reducing the met- and oxy-forms to the deoxy-form in an anaerobic environment. This spectroscopic method provides a qualitatively rapid laboratory screening procedure for food control to unmask the presence of CO in frozen or fresh fish. (c) 2006 Elsevier Ltd. All rights reserved

The Correlation Between Historical and Instrumental Seismicity in the Sansepolcro Basin, Northern Apennines, Italy

The area investigated, the Sansepolcro basin, is characterized by the presence of important earthquakes in the past with estimated intensity even larger than IX MCS (the 1352 Monterchi earthquake, the 1389 Boccaserriola, the 1458 Citta’ di Castello, the 1781 Cagliese and the 1917 Monterchi-Citerna earthquakes, CPTI Working Group, 2004) and by a surprisingly scarce instrumental seismicity compared to the adjacent areas struck by high seismicity (Castello et al., 2005; Ciaccio et al., 2006). The area north of Sansepolcro has been struck in recent years by four minor sequences, occurred between 1987 and 2001 with magnitude ranging from Ml3.0 to Mw4.7. In this work we analyse the most important earthquakes of the 20th century occurred in the Altotiberina Valley in 1917, 1918, 1919 and 1948; in particular instrumental relocation, focal mechanisms and Ms and Mw magnitude estimation are re-evaluated. The relocation of these earthquakes is particularly critical and is an important issue. An instrumental and precise location is critical for the complexity of the problems associated with the study of seismograms prior to the first half of the twentieth century and is relevant because in the surrounding regions higher seismicity is observed. Regarding this peculiarity of the area, it’s very important to detect the location of the historical earthquakes: in particular, the 1917 event is often associated to the possibility that the regional low angle Altotiberina Fault (Barchi et al., 1998) is able or not to nucleate large- or moderate-magnitude events, being historically located close to its surface (Boncio and Lavecchia, 2000)