Microsimulation Models to Inform Colorectal Cancer Screening Decisions: From validated tools to tailoring recommendations

The aim of this thesis is to first describe the steps that are required to standardize the structure of a microsimulation model (as MISCAN-Colon) and make it as the core of an online user-friendly model application. Briefly, these steps include: i) assessing effectiveness of CRC screening in different screening settings; ii) validating the model structure and its assumptions; and iii) building an online user-friendly platform that allow users to easily upload country-specific data, adjust a model, and simulate future outcomes of CRC screening in their countries. Subsequently, this thesis aims to demonstrate how models can be used to help policymakers in their decisions about CRC screening regarding populations at different risk of CRC

A network simplification approach to ease topological studies about the food-web architecture

Food webs studies are intrinsically complex and time-consuming. Network data about trophic interaction across different large locations and ecosystems are scarce in comparison with general ecological data, especially if we consider terrestrial habitats. Here we present a complex network strategy to ease the gathering of the information by simplifying the collection of data with a taxonomic key. We test how well the topology of three different food webs retain their structure at the resolution of the nodes across distinct levels of simplification, and we estimate how community detection could be impacted by this strategy. The first level of simplification retains most of the general topological indices; betweenness and trophic levels seem to be consistent and robust even at the higher levels of simplification. This result suggests that generalisation and standardisation, as a good practice in food webs science, could benefit the community, both increasing the amount of open data available and the comparison among them, thus providing support especially for scientists that are new in this field and for exploratory analysis

Mild oxidative Csp3-H bond functionalization applied for the synthesis, ring expansion and derivatization of heterocycles

Csp3-H bonds are ubiquitous in natural and synthetic molecules, but chemists are still struggling to develop general and convenient methodologies for a gentle and direct activation of such bonds. Indeed, new mild and regioselective processes involving the oxidative functionalization of high energetic Csp3-H bonds are highly desirable, especially when valuable heterocyclic scaffolds are involved. Following this perspective, in this thesis are presented my results on the mild Csp3-H bond oxidative activation involved in the synthesis, ring expansion and functionalization of heterocycles. In Chapter 2, two different approaches in which the oxidative C-H functionalization is applied on the formation of reactive dipolar species trapped in-situ by dipolar cycloaddition are shown. In this context, the TEMPO mediated formal “dehydrogenation” of N-carbamoyl protected hydroxylamines, and the consequent trapping of the generated unstable nitrones were proposed. This methodology resulted as a very efficient approach for the synthesis of several N-acyl and N-carbomoyl isoxazolines, allowing also the reaction with more challenging substrate, such as alkyl and allyl hydroxylamine. Furthermore, a two-step one-pot azide formation/click-reaction preliminary study was displayed. The reaction consisted in a copper/hydroxylperoxide mediated Csp3-H activation, addition of trimethylsilyl-azide and the consecutive click-reaction step. This strategy, in its simplicity, resulted very versatile, and it allowed the formation of poly-heterocycles from unstable azide substituted systems. In Chapter 3, applications of diazocompounds in expansion ring reaction of heterocycles via Csp3-H oxidative functionalization were further explored. Following the experience grown in the García’s group, a novel methodology for the synthesis of demanding benzoazepine scaffold via TEMPO salt mediated Csp3-H oxidative functionalization/ring expansion of common tetrahydroisoquinoline was developed. Furthermore, a new synthetic pathway for a high value anti-obesity drug, so called Lorcaserin was porposed. Finally, a preliminary study for the achievement of a one-step Csp3-H bond functionalization/N-based expansion ring were displayed. In Chapter 4, a novel oxidative activation/Ugi-type reaction was proposed. This strategy allowed for the first time the functionalization of benzylic Csp3-H bonds following a Ugi-type approach. In this way, several 9-imide acridanes and xanthenes were prepared, and the acridane scaffolds resulted a precursor of a novel and potent class of organo-photocatalyst. In addition, the proposed approach was also efficiently enrolled in the functionalization of other classes of substrate

Elachistocleis haroi Pereyra, Akmentins, Laufer & Vaira, 2013 (Anura: Microhylidae) en Paraguay

Elachistocleis haroi (Anura: Microhylidae) fue descrita de las Provincias de Jujuy, Salta y Formosa en Argentina y el departamento Tarija en Bolivia. Sobre la base de ejemplares albergados en el Museo Nacional de Historia Natural del Paraguay y Colección Zoológica de la Facultad de Ciencias Exactas y Naturales, extendemos la distribución conocida de la especie a los departamentos de Alto Paraguay, Boquerón y Presidente Hayes, en la Región Occidental de Paraguay.Elachistocleis haroi (Anura: Microhylidae) was described from the provinces of Jujuy, Salta and Formosa in Argentina and the Tarija department in Bolivia. Based on specimens housed in the Museo Nacional de Historia Natural del Paraguay and Colección Zoológica de la Facultad de Ciencias Exactas y Naturales, we extend the range of the species to the departments of Alto Paraguay, Boquerón and Presidente Hayes, in western Paraguay.Fil: Caballero Gini, Andrea. Universidad Nacional de Asuncion; ParaguayFil: Bueno Villafañe, Diego. Universidad Nacional de Asuncion; Paraguay. Museo Nacional de Historia Natural del Paraguay; ParaguayFil: Romero Nardelli, L.. Universidad Nacional de Asuncion; ParaguayFil: Lavilla, Esteban Orlando. Fundación Miguel Lillo. Dirección de Zoología. Instituto de Herpetología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán; Argentin

Optimizing screening with faecal immunochemical test for both sexes - Cost-effectiveness analysis from Finland

Publisher Copyright: © 2022 The AuthorsA faecal immunochemical test (FIT) screening pilot was introduced in Finland in 2019 with sex-specific screening strategies. This study aims to model cost-effectiveness of sex-specific strategies for the whole population, and to assess whether the current strategies are optimal. We developed separate MISCAN-Colon models, including different FIT performances, for the Finnish men and women using the first-year data of the FIT screening pilot. We evaluated 180 FIT strategies varying in FIT cut-off, screening interval, age to start, and age to stop screening, and compared them to no-screening by sex. We used incremental cost-effectiveness ratios (ICERs) to identify the optimal strategy after combining all male and female strategies and restricting the analysis by costs and referral rate to diagnostic colonoscopies. Offering annual FIT screening with a cut-off of 25 μg/g at 50–79 years in men and with a cut-off of 10 μg/g at 55–69 years in women was optimal. This combined strategy prevented 28% of colorectal cancer (CRC) cases and 55% of CRC deaths with acceptable costs (ICER = 9000€/life-years gained). Screening at the current target age of 60–74 years was suboptimal for both sexes. Among strategies with the same target age and interval for both sexes, expected benefits from optimal screening were lower but still reasonable. Our results support a wider age range of screening in men, and a lower cut-off for a positive test in women when restrictions on colonoscopy capacity and costs are in place. National FIT screening program should start at younger age.Peer reviewe

Ontogenetic changes in the ventral colouration of post metamorphic Elachistocleis haroi Pereyra, Akmentins, Laufer, Vaira, 2013 (Anura: Microhylidae)

Ontogenetic colour change (OCC) is defined as the progressive and non-reversible process of changes in colouration of organisms associated with their development. Among the many vertebrate groups, amphibians are particularly impressive for their strikingly wide variety of colours, colour patterns, and signals, whose evolutionary and ecological significance have been poorly studied.CONACYT – Consejo Nacional de Ciencia y TecnologíaPROCIENCI

First formal records of Stenocercus doellojuradoi (Freiberg, 1944) (Squamata, Tropiduridae) from the Paraguayan Chaco

Stenocercus is a genus widely distributed geographically and ecologically, from the north of the Andes mountain range and surrounding lowlands, to southern Brazil and central Argentina. Herein we present the first records of Stenocercus doellojuradoi for Paraguay. We discussed morphological variations found in the specimens of Paraguay, in addition to possible threats to the conservation of the species in the locality where it was recorded.Asociación Herpetológica Argentin

Development and validation of a case-finding algorithm for the identification of non-small cell lung cancers in a region-wide Italian pathology registry

PurposeTo 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 methodsData 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.ResultsThe 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%.ConclusionsThe 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

Sex differences in the utilization of drugs for COVID-19 treatment among elderly residents in a sample of Italian nursing homes

PurposeTo describe the use of hydroxychloroquine (HCQ), azithromycin (AZI) and low-molecular-weight-heparins (LMWH) by sex among elderly residents in nursing homes (NHs) of Tuscany region (Italy) during the first pandemic peak.MethodsA population-based drug utilization study was performed linking the Tuscany Administrative Databases (TAD) to the regional COVID-19 registry. Among elderly patients (>= 65years old) registered in TAD on 1st December 2019, new users of HCQ, AZI and LMWH that started the treatment during NHs stay (i.e., no dispensing of the same drug during the previous 6months) were respectively identified in each month of observation period (December 2019-May 2020). The percentage of subjects diagnosed with COVID-19 (COVID-19+) on, or before, the date of first dispensing of the drug of interest was described. Results were stratified by sex (male = M; female = F).ResultsNew users of HCQ, AZI and LMWH were 62, 300, and 1215, respectively. About 95% of HCQ new users received the drug in April (M = 20; F = 40) of which 11 of men (55%) and 25 of women (62%) were COVID-19+; AZI new users in April (M = 32; F = 83) were two-fold compared to February, of which 10 of men (31%) and 30 of women (36%) were COVID-19+; LMWH new users showed a peak in April (M = 74; F = 142), when 31% of men and 34% of women were COVID-19+.ConclusionsNew users showed a peak during the first pandemic wave and females were over two-fold compared to men. HCQ was often prescribed in absence of COVID-19 diagnosis. During future global emergencies drug prescriptions should better be monitored in frail populations, especially in case of drugs with uncertain efficacy and safety