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The paper discusses results of an interdisciplinary research project integrating lead isotope, chemical, and archaeological analysis of 20 early metal objects from central Italy. The aim of the research was to develop robust provenance hypotheses for 4th and 3rd millennia BC metals from an important, yet hitherto neglected, metallurgical district in prehistoric Europe, displaying precocious copper mining and smelting, as well as socially significant uses of metals in 'Rinaldone-style' burials. All major (and most minor) ore bodies from Tuscany and neighbouring regions were characterised chemically and isotopically, and 20 Copper Age axe-heads, daggers and halberds were sampled and analysed. The objects were also reassessed archaeologically, paying special attention to find context, typology, and chronology. This multi-pronged approach has allowed us to challenge received wisdom concerning the local character of early metal production and exchange in the region. The research has shown that most objects were likely manufactured in west-central Italy using copper from Southern Tuscany and, quite possibly, the Apuanian Alps. A few objects, however, display isotopic and chemical signatures compatible with the Western Alpine and, in one case, French ore deposits. This shows that the Copper Age communities of west-central Italy participated in superregional exchange networks tying together the middle/upper Tyrrhenian region, the western Alps, and perhaps the French Midi. These networks were largely independent from other metal displacement circuits in operation at the time, which embraced the north-Alpine region and the south-eastern Alps, respectively. [ABSTRACT FROM AUTHOR]

Background: The geothermal power plants for electricity production currently active in Italy are all located in Mt. Amiata area in the Tuscany region. A cross-sectional survey was conducted in the framework of the regional project "InVETTA—Biomonitoring Survey and Epidemiological Evaluations for the Protection of Health in the Amiata Territories", using objective measures of lung function to investigate the role of hydrogen sulphide (H2S) in affecting the respiratory health of the population living in this area. Methods: 2018 adults aged 18–70 were enrolled during 2017–2019. Home and workplace addresses of participants were geocoded. Dispersion modelling was used to evaluate the spatial variability of exposure to H2S from the geothermal power plants' emissions. We estimated average long-term historical exposure to H2S and more recent exposure indicators. Chronic Obstructive Pulmonary Disease (COPD) was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Multivariable logistic regressions were performed to investigate associations between outcome and exposure. Results: Our findings did not showed any evidence of an association between increasing H2S exposure and lung function impairments. Some risk reductions were observed: a -32.8% (p = 0.003) for FEV1<80% and a -51.7% (p = 0.001) risk decrease for FVC<80% were associated with interquartile increase (13.8 μg/m3) of H2S levels. Conclusion: Our study provides no evidence that chronic exposure to low levels of H2S is associated with decrements in pulmonary function, suggesting that ambient H2S exposure may benefit lung function. [ABSTRACT FROM AUTHOR]

Introduction: Nowadays, most of the research studies in the field of adolescent gambling are focused on individual factors related to problem gambling. The aim of this study was to test an integrated model to explain adolescent problem gambling involving both individual (i.e., correct gambling knowledge, superstitious thinking, and gambling-related cognitive distortions) and environmental factors (i.e., parental gambling frequency). In detail, the aim was to better understand the role of parental gambling behavior on adolescents' gambling frequency and problem gambling severity, to draw indications for prevention. Methods: Participants were 680 parents (36% men; Mage = 48.32, SD = 6.14 years) of 680 high school students (51% boys; Mage = 15.51, SD =.55 years) attending the second year of different high schools in Tuscany (Italy). Data collection occurred within the school prevention program PRIZE (Prevention of gambling risk among adolescents). Results: A path model showed was conducted to detect direct and indirect effects from individual and environmental factors to gambling problem severity. Analyses showed that correct gambling knowledge and superstitious thinking were directly related–respectively in a negative and a positive direction–both to gambling-related cognitive distortions and adolescents' gambling frequency. Parental gambling frequency was directly associated with adolescents' gambling frequency. Correct gambling knowledge and superstitious thinking were indirectly related to adolescents' gambling problem severity through the mediational role of gambling-related cognitive distortions and gambling frequency. Parental gambling frequency was indirectly linked to gambling problem severity by passing through adolescents' gambling frequency. Conclusions: The current cross-sectional results confirm that parental gambling behavior has an important role for adolescents' gambling behavior and severity. Thus, results highlight the need for innovative prevention programs which involve adolescents' adult reference figures and integrate the individual risk and protective factors with the environmental ones. [ABSTRACT FROM AUTHOR]

Background: In Italy, abortion services are public: therefore, health Institutions should provide clear and easily readable web-based information. We aimed to 1) assess variation in abortion services utilisation; 2) analyse the readability of institutional websites informing on induced abortion; 3) explore whether easier-to-read institutional websites influenced the correct fruition of abortion services. Methods: We identified from the 2021 administrative databases of Tuscany all women having an abortion, and–among them–women having an abortion with the certification provided by family counselling centres, following the pathway established by law. We assessed variation in total and certified abortion rates by computing the Systematic Component of Variation. We analysed the readability of the Tuscan health authorities' websites using the readability assessment tool READ-IT. We explored how institutional website readability influenced the odds of having certified abortions by running multilevel logistic models, considering health authorities as the highest-level variables. Results: We observed high variation in the correct utilization of the abortion pathway in terms of certified abortion rates. The READ-IT scores showed that the most readable text was from the Florence Teaching Hospital website. Multilevel models revealed that higher READ-IT scores, corresponding to more difficult texts, resulted in lower odds of certified abortions. Conclusions: Large variation in the proper fruition of abortion pathways occurs in Tuscany, and such variation may depend on readability of institutional websites informing on induced abortion. Therefore, health Institutions should monitor and improve the readability of their websites to ensure proper and more equitable access to abortion. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a case-finding algorithm for the identification of Non-Small Cell Lung Cancer (NSCLC) cases in a region-wide Italian pathology registry (PR). Materials and methods: Data collected between 2009 and 2017 in the PR and the Pharmacy Database of the University Hospital of Siena and the PR of Tuscany region were used. A NSCLC-identification algorithm based on free-text keywords and SNOMED morphology and topography codes was designed and tested on data from Siena: indication for drug use (i.e. NSCLC) was the reference standard for sensitivity (SE); positive predictive value (PPV) was estimated through manual review. Algorithm modifications were then tested to improve algorithm performance: PPV was calculated against validated dataset from PR of Siena; a range of SE [min-max] was estimated in PR of Tuscany using analytical formulae that assumed NSCLC incidence equal either to 80% or 90% of overall lung cancer incidence recorded in Tuscany. The algorithm modification with the best performance was chosen as the final version of the algorithm. A random sample of 200 cases was extracted from the PR of Tuscany for manual review. Results: The first version of the algorithm showed a PPV of 74.7% and SE of 79% in PR of Siena. The final version of the algorithm had a SE in PR of Tuscany that grew with calendar time (2009 = [24.7%-28%]; 2017 = [57.9%-65.1%]) and a PPV of 93%. Conclusions: The final NSCLC-finding algorithm showed with very high PPV. SE was in line with the expected contribution of PR to overall cases captured in the regional Cancer Registry, with a trend of increase over calendar time. Given the promising algorithm validity and the wide use of SNOMED terminology in electronic pathology records, the proposed algorithm is expected to be easily adapted to other electronic databases for (pharmaco)epidemiology purposes. [ABSTRACT FROM AUTHOR]

With the aim of studying the spread of the SARS-CoV-2 infection in the Tuscany region of Italy during the first epidemic wave (February-June 2020), we define a compartmental model that accounts for both detected and undetected infections and assumes that only notified cases can die. We estimate the infection fatality rate, the case fatality rate, and the basic reproduction number, modeled as a time-varying function, by calibrating on the cumulative daily number of observed deaths and notified infected, after fixing to plausible values the other model parameters to assure identifiability. The confidence intervals are estimated by a parametric bootstrap procedure and a Global Sensitivity Analysis is performed to assess the sensitivity of the estimates to changes in the values of the fixed parameters. According to our results, the basic reproduction number drops from an initial value of 6.055 to 0 at the end of the national lockdown, then it grows again, but remaining under 1. At the beginning of the epidemic, the case and the infection fatality rates are estimated to be 13.1% and 2.3%, respectively. Among the parameters considered as fixed, the average time from infection to recovery for the not notified infected appears to be the most impacting one on the model estimates. The probability for an infected to be notified has a relevant impact on the infection fatality rate and on the shape of the epidemic curve. This stresses the need of collecting information on these parameters to better understand the phenomenon and get reliable predictions. [ABSTRACT FROM AUTHOR]

Background: Genetic analyses have recently been carried out on present-day Tuscans (Central Italy) in order to investigate their presumable recent Near East ancestry in connection with the long-standing debate on the origins of the Etruscan civilization. We retrieved mitogenomes and genome-wide SNP data from 110 Tuscans analyzed within the context of The 1000 Genome Project. For phylogeographic and evolutionary analysis we made use of a large worldwide database of entire mitogenomes (>26,000) and partial control region sequences (>180,000). Results: Different analyses reveal the presence of typical Near East haplotypes in Tuscans representing isolated members of various mtDNA phylogenetic branches. As a whole, the Near East component in Tuscan mitogenomes can be estimated at about 8%; a proportion that is comparable to previous estimates but significantly lower than admixture estimates obtained from autosomal SNP data (21%). Phylogeographic and evolutionary inter-population comparisons indicate that the main signal of Near Eastern Tuscan mitogenomes comes from Iran. Conclusions: Mitogenomes of recent Near East origin in present-day Tuscans do not show local or regional variation. This points to a demographic scenario that is compatible with a recent arrival of Near Easterners to this region in Italy with no founder events or bottlenecks. [ABSTRACT FROM AUTHOR]

Arboviral infections have repeatedly been reported in the republic of Djibouti, consistent with the fact that essential vectors for arboviral diseases are endemic in the region. However, there is a limited recent information regarding arbovirus circulation, and the associated risk predictors to human exposure are largely unknown. We performed, from November 2010 to February 2011 in the Djibouti city general population, a cross-sectional ELISA and sero-neutralisation-based sero-epidemiological analysis nested in a household cohort, which investigated the arboviral infection prevalence and risk factors, stratified by their vectors of transmission. Antibodies to dengue virus (21.8%) were the most frequent. Determinants of infection identified by multivariate analysis pointed to sociological and environmental exposure to the bite of Aedes mosquitoes. The population was broadly naïve against Chikungunya (2.6%) with risk factors mostly shared with dengue. The detection of limited virus circulation was followed by a significant Chikungunya outbreak a few months after our study. Antibodies to West Nile virus were infrequent (0.6%), but the distribution of cases faithfully followed previous mapping of infected Culex mosquitoes. The seroprevalence of Rift valley fever virus was 2.2%, and non-arboviral transmission was suggested. Finally, the study indicated the circulation of Toscana-related viruses (3.7%), and a limited number of cases suggested infection by tick-borne encephalitis or Alkhumra related viruses, which deserve further investigations to identify the viruses and vectors implicated. Overall, most of the arboviral cases' predictors were statistically best described by the individuals' housing space and neighborhood environmental characteristics, which correlated with the ecological actors of their respective transmission vectors' survival in the local niche. This study has demonstrated autochthonous arboviral circulations in the republic of Djibouti, and provides an epidemiological inventory, with useful findings for risk mapping and future prevention and control programs. Author Summary: The arboviruses are a group of viruses transmitted by arthropods such as mosquitoes, ticks, or sandflies. These pathogens have complex life cycles and depend on both arthropods and vertebrate hosts for survival and transmission. Recent global increase in cases confirms that they are of great public health concern. In this study, conducted in the winter of 2010, the seroprevalence and determinants of infections were investigated in the republic of Djibouti, Horn of Africa. The highest seroprevalence values were observed for mosquito-borne diseases, in particular dengue (transmitted by Aedes mosquitoes); antibodies to dengue virus were found in a fifth of the sampled population. Most Djiboutians were initially unexposed to Chikungunya virus (also transmitted by Aedes mosquitoes), but a few months later, many got infected, resulting in an outbreak. Of the few West Nile virus seropositive cases detected, the majority were in places where WNV had been previously identified in Culex mosquitoes. In addition, seropositive cases of Toscana-related viruses (transmitted by sandflies), and tick-borne encephalitis virus or Alkhumra-related viruses (transmitted by ticks) were also observed. In this study, the risk of arboviral infections was mostly associated with environmental and behavioural risk factors, with highest risk prevailing in the city centre (District 1). Overall, the results suggest a likely exposure to the local circulation of arboviruses, rather than infections acquired outside the study area. This knowledge, therefore, confirms the impact of arbovirus infections in Djibouti, and is essential for prevention and control programs. [ABSTRACT FROM AUTHOR]

Background: In most countries, men seem to be more susceptible to tuberculosis (TB) than women, but only few studies have investigated the reasons of this gender incidence difference. The effect of sexual hormones on immunity is possible. Methods: Data from children and adults, living in Tuscany, hospitalized for TB in all the thirty-one regional hospitals from January 1st 1997 to December 31st 2011, were analyzed using the International Classification of Disease, 9th Revision, Clinical Modification. Results: During the study period, 10,744 patients were hospitalized with TB diagnosis, precisely 279 (2.6%) children [0–14 years], 205 (1.9%) adolescents [15–18 years] and 10,260 (95.5%) adults [≥18 years]. The male population ranged from 249 patients (51.4%) in children and adolescents, to 6,253 (60.9%) in adults. Pulmonary TB was the most common form both in children and adults. Men were more likely than women to have pulmonary TB after puberty, while no significant differences were found between males and females in the hospitalized children. The male gender also resulted the most affected for the extra-pulmonary disease sites, excluding the lymphatic system, during the reproductive age. Conclusions: Our findings suggest a possible role of sexual hormones in the development of TB. No significant male-female difference was found in TB incidence among children, while a sex ratio significantly different from 1∶1 emerged among reproductive age classes. An increased incidence difference also persisted in older men, suggesting that male-biased risk factors could influence TB progression. Some limitations of the study are the sample size, the method of discharge diagnosis which could be deficient in accuracy in some cases, the increasing number of immigrants and the lack of possible individual risk factors (smoke and alcohol). Further studies are needed to investigate the possible hormone-driven immune mechanisms determining the sexual dimorphism in TB. [ABSTRACT FROM AUTHOR]

We tested the predictions of three models (female preference; hotspot; predator avoidance) on lek formation in the fallow deer population of San Rossore, Tuscany. We collected behavioural observations in two leks and radiotracking data on 67 deer over 7 years. Two deer sub-populations were present in the northern and southern sides of the area, respectively, the two sectors being delimited by a river and including one lek each. Predictions were tested for one lek (SG), located in the south-side where we set up our 7-year radiotracking program. Data from a second lek (FO, north-side) were used to test those predictions which imply the occurrence of multiple leks in the same population. We showed that the majority of females made one single visit to one lek, only during the rut. The lek was located outside areas of higher female traffic and home range overlap, and females increased home range sizes during the rut to reach it. Twilight routes of females never crossed the lek; instead, females walked atypical routes and at a faster pace to reach the lek and mate. The distance between the two leks was higher than the average diameter of female home ranges, and only one lek was present within female home ranges. Males reached the lek one month before the arrival of females, corroborating that lekking is a female-initiated process (females moving towards large clumped male aggregations) rather than a male-initiated process (males moving towards female hotspots). Our results supported the female preference model, and rejected the predictions of the hotspot model. Also, leks were located far from areas with higher predation risk, supporting the predator avoidance model. The position of lek SG resulted ‘handy’ at the sub-population level because of the optimal trade-off between travel costs for females to reach it and avoidance of human predators. [ABSTRACT FROM AUTHOR]

Background: In northern Tunisia, the co-circulation of two related sand fly-borne phleboviruses, Toscana virus (TOSV) and Punique virus (PUNV) was previously demonstrated. In contrast to TOSV, a prominent human pathogen, there is no data supporting that PUNV is capable to infect and cause disease to humans. We studied the respective involvement of TOSV and PUNV in human infections in northern Tunisia through a seroprevalence study. Methods: The presence of TOSV and PUNV neutralising antibodies (NT-Ab) was tested in human sera collected from 5 districts of the governorate of Bizerte, and the titres of NT-Ab were estimated by microneutralisation (MN) assay. Principal Findings: A total of 1,273 sera were processed. TOSV and PUNV NT-Ab were detected in 522 (41%) and 111 sera (8.72%) respectively. TOSV seroprevalence varied from 17.2% to 59.4% depending on the district. Analysis of TOSV geometric mean titre values demonstrated a constant increase according to the age. The vast majority of sera containing NT-Ab were found to be more reactive toward TOSV than PUNV. Indeed, past infections with PUNV and TOSV were undisputable for 5 and 414 sera, respectively. Conclusions: PUNV may be capable to infect humans but at a low rate. TOSV is responsible for the vast majority of human infections by sand fly-borne phleboviruses in northern Tunisia. TOSV must be considered by physician and tested in diagnostic laboratories for patients with meningitis and unexplained fever in northern Tunisia. Author Summary: In northern Tunisia, two different pheboviruses are known to circulate in sand fly population, Toscana virus (TOSV) and Punique virus (PUNV). In contrast to TOSV, a prominent human pathogen, there is no data supporting that PUNV is capable to infect humans and to cause a disease. We studied the respective involvement of TOSV and PUNV in human infections in northern Tunisia through a seroprevalence study. Because TOSV and PUNV are antigenically and genetically closely related, it is difficult to distinguish between them by using broadly reactive serological tests, such as enzyme-linked immunosorbent assay (ELISA). Thus, we developed a method of microneutralisation assay using the two viruses in a comparative manner. A total of 1,273 sera were processed. We provide first evidence to support (i) that Punique virus may be capable to infect humans but at a low rate, (ii) that TOSV, the most prevalent arbovirus in Southern Europe, is responsible for the vast majority of human infections by sand fly-borne phleboviruses in northern Tunisia. Therefore, it is important to consider TOSV as an important pathogen that needs to be included in all virological diagnostic concerning patients with meningitis and unexplained febrile illness originated from Northern Tunisia. [ABSTRACT FROM AUTHOR]

Nucleoproteins (NPs) encapsidate the Phlebovirus genomic (-)RNA. Upon recombinant expression, NPs tend to form heterogeneous oligomers impeding characterization of the encapsidation process through crystallographic studies. To overcome this problem, we set up a standard protocol in which production under both non-denaturing and denaturing/refolding conditions can be investigated and compared. The protocol was applied for three phlebovirus NPs, allowing an optimized production strategy for each of them. Remarkably, the Rift Valley fever virus NP was purified as a trimer under native conditions and yielded protein crystals whereas the refolded version could be purified as a dimer. Yields of trimeric Toscana virus NP were higher from denaturing than from native condition and lead to crystals. The production of Sandfly Fever Sicilian virus NP failed in both protocols. The comparative protocols described here should help in rationally choosing between denaturing or non-denaturing conditions, which would finally result in the most appropriate and relevant oligomerized protein species. The structure of the Rift Valley fever virus NP has been recently published using a refolded monomeric protein and we believe that the process we devised will contribute to shed light in the genome encapsidation process, a key stage in the viral life cycle. Author Summary: Phleboviruses have a worldwide distribution and are usually represented by their prototype Rift Valley fever virus that can have a great impact on health and economy in Africa. The genome of phleboviruses is a segmented negative strand RNA that is encapsidated by the nucleoprotein. The structure of the monomeric nucleoprotein has been recently published but it's not sufficient to decipher a convincing mechanism for the nucleoprotein oligomerization. In order to understand this key step in the virus life cycle, the purification of oligomers homogeneous in size would be a key step to launch structural studies. To that aim, a procedure relying on recombinant protein production in both denaturing and non-denaturing conditions was applied to three phlebovirus nucleoproteins. Although the best production pipeline differs for each protein, pure and homogeneous solutions of Rift Valley fever virus and Toscana virus nucleoproteins were successfully obtained. Both proteins, behaving as apparent trimers in solution, lead to protein crystallization, a starting point to understand the genome encapsidation through structural studies. [ABSTRACT FROM AUTHOR]