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The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS-STING (cyclic GMP-AMP synthase-signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma.

We describe the main structure and outcomes of the new probabilistic seismic hazard model for Italy, MPS19 [Modello di Pericolosità Sismica, 2019]. Besides to outline the probabilistic framework adopted, the multitude of new data that have been made available after the preparation of the previous MPS04, and the set of earthquake rate and ground motion models used, we give particular emphasis to the main novelties of the modeling and the MPS19 outcomes. Specifically, we (i) introduce a novel approach to estimate and to visualize the epistemic uncertainty over the whole country; (ii) assign weights to each model components (earthquake rate and ground motion models) according to a quantitative testing phase and structured experts’ elicitation sessions; (iii) test (retrospectively) the MPS19 outcomes with the horizontal peak ground acceleration observed in the last decades, and the macroseismic intensities of the last centuries; (iv) introduce a pioneering approach to build MPS19_cluster, which accounts for the effect of earthquakes that have been removed by declustering. Finally, to make the interpretation of MPS19 outcomes easier for a wide range of possible stakeholders, we represent the final result also in terms of probability to exceed 0.15 g in 50 years., peer-reviewed

Background The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Methods and analysis Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the “PROVENT-C19 Registry”, endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care…’(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. Conclusions This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. Trial registration The registry was registered (ClinicalTrial.Gov Trials Register NCT04905875) on May 28,2021.

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade., The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.

Background/Objective: Idiopathic REM sleep behavior disorder (iRBD) often precedes Parkinson's disease (PD) and other alpha-synucleinopathies. The aim of the study is to investigate brain glucose metabolism of patients with RBD and PD by means of a multidimensional scaling approach, using18F-FDG-PET as a biomarker of synaptic function. Methods: Thirty-six iRBD patients (64.1±6.5 y, 32 M), 72 PD patients, and 79 controls (65.6±9.4 y, 53 M) underwent brain 18 F-FDG-PET. PD patients were divided according to the absence (PD, 32 subjects; 68.4±8.5 y, 15 M) or presence (PDRBD, 40 subjects; 71.8±6.6 y, 29 M) of RBD. 18F-FDG-PET scans were used to independently discriminate subjects belonging to four categories: Controls (RBD no, PD no), iRBD (RBD yes, PD no), PD (RBD no, PD yes) and PDRBD (RBD yes, PD yes). Results: The discriminant analysis was moderately accurate in identifying the correct category. This is because the model mostly confounds iRBD and PD, thus the intermediate classes. Indeed, iRBD, PD and PDRBD were progressively located at increasing distance from controls and are ordered along a single dimension (principal coordinate analysis) indicating the presence of a single flux of variation encompassing both RBD and PD conditions. Conclusion: Data-driven approach to brain 18 F-FDG-PET showed only moderate discrimination between iRBD and PD patients, highlighting brain glucose metabolism heterogeneity among such patients. iRBD should be considered as a marker of an ongoing condition that may be picked-up in different stages across patients and thus express different brain imaging features and likely different clinical trajectories.

The alkenone unsaturation index, U37K', has now proven its worth as a tool for paleothermometry. U37K' measured in most modern sediments throughout the World Ocean can be translated using established calibrations into realistic, seemingly reliable estimates of mean annual temperature at the sea surface (SST). However, it remains mysterious why water temperature estimates based on this biotic index correspond to "mean annual" SST and whether such estimates apply back in geological time. Solving these mysteries is imperative and will require thoughtful, concerted research effort by the biological, chemical, and geological oceanographic community. This report summarizes what is now known about alkenones, in particular, their use in estimating the growth temperature of specific haptophyte algae that synthesize and export these compounds to the marine sediment record. It highlights future field and laboratory research directions that should be taken to clarify and bolster utility of alkenones as a generally valued paleoceanographic tool.

The NEAM Tsunami Hazard Model 2018 (NEAMTHM18) is a probabilistic hazard model for tsunamis generated by earthquakes. It covers the coastlines of the North-eastern Atlantic, the Mediterranean, and connected seas (NEAM). NEAMTHM18 was designed as a three-phase project. The first two phases were dedicated to the model development and hazard calculations, following a formalized decision-making process based on a multiple-expert protocol. The third phase was dedicated to documentation and dissemination. The hazard assessment workflow was structured in Steps and Levels. There are four Steps: Step-1) probabilistic earthquake model; Step-2) tsunami generation and modeling in deep water; Step-3) shoaling and inundation; Step-4) hazard aggregation and uncertainty quantification. Each Step includes a different number of Levels. Level-0 always describes the input data; the other Levels describe the intermediate results needed to proceed from one Step to another. Alternative datasets and models were considered in the implementation. The epistemic hazard uncertainty was quantified through an ensemble modeling technique accounting for alternative models’ weights and yielding a distribution of hazard curves represented by the mean and various percentiles. Hazard curves were calculated at 2,343 Points of Interest (POI) distributed at an average spacing of ∼20 km. Precalculated probability maps for five maximum inundation heights (MIH) and hazard intensity maps for five average return periods (ARP) were produced from hazard curves. In the entire NEAM Region, MIHs of several meters are rare but not impossible. Considering a 2% probability of exceedance in 50 years (ARP≈2,475 years), the POIs with MIH >5 m are fewer than 1% and are all in the Mediterranean on Libya, Egypt, Cyprus, and Greece coasts. In the North-East Atlantic, POIs with MIH >3 m are on the coasts of Mauritania and Gulf of Cadiz. Overall, 30% of the POIs have MIH >1 m. NEAMTHM18 results and documentation are available through the TSUMAPS-NEAM project website (http://www.tsumaps-neam.eu/), featuring an interactive web mapper. Although the NEAMTHM18 cannot substitute in-depth analyses at local scales, it represents the first action to start local and more detailed hazard and risk assessments and contributes to designing evacuation maps for tsunami early warning. © Copyright © 2021 Basili, Brizuela, Herrero, Iqbal, Lorito, Maesano, Murphy, Perfetti, Romano, Scala, Selva, Taroni, Tiberti, Thio, Tonini, Volpe, Glimsdal, Harbitz, Løvholt, Baptista, Carrilho, Matias, Omira, Babeyko, Hoechner, Gürbüz, Pekcan, Yalçıner, Canals, Lastras, Agalos, Papadopoulos, Triantafyllou, Benchekroun, Agrebi Jaouadi, Ben Abdallah, Bouallegue, Hamdi, Oueslati, Amato, Armigliato, Behrens, Davies, Di Bucci, Dolce, Geist, Gonzalez Vida, González, Macías Sánchez, Meletti, Ozer Sozdinler, Pagani, Parsons, Polet, Power, Sørensen and Zaytsev.

Background Pollution has been suggested as a precipitating factor for cardiovascular diseases. However, data about the link between air pollution and the risk of out-of-hospital cardiac arrest (OHCA) are limited and controversial. Methods By collecting data both in the OHCA registry and in the database of the regional agency for environmental protection (ARPA) of the Lombardy region, all medical OHCAs and the mean daily concentration of pollutants including fine particulate matter (PM10, PM2.5), benzene (C6H6), carbon monoxide (CO), nitrogen dioxide (NO2), sulphur dioxide (SO2), and ozone (O3) were considered from January 1st to December 31st, 2019 in the southern part of the Lombardy region (provinces of Pavia, Lodi, Cremona and Mantua; 7863 km2; about 1550000 inhabitants). Days were divided into high or low incidence of OHCA according to the median value. A Probit dose-response analysis and both uni- and multivariable logistic regression models were provided for each pollutant. Results The concentrations of all the pollutants were significantly higher in days with high incidence of OHCA except for O3, which showed a significant countertrend. After correcting for temperature, a significant dose-response relationship was demonstrated for all the pollutants examined. All the pollutants were also strongly associated with high incidence of OHCA in multivariable analysis with correction for temperature, humidity, and day-to-day concentration changes. Conclusions Our results clarify the link between pollutants and the acute risk of cardiac arrest suggesting the need of both improving the air quality and integrating pollution data in future models for the organization of emergency medical services.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases. © 2021 The Authors, some rights reserved.

In this Perspective, owing to an error in the HTML, the surname of author Alejandro López-Tobón of the LifeTime Community Working Groups consortium was indexed as ‘Tobon’ rather than ‘López-Tobón’ and the accents were missing. The HTML version of the original Perspective has been corrected; the PDF and print versions were always correct. © 2021, The Author(s).

Rationale In Parkinson’s disease (PD), spatial covariance analysis of 18F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP). Methods The PDRPNL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRPIT was identified in 20 controls and 20 “de-novo” PD patients from an Italian cohort. A further 24 controls and 18 “de-novo” Italian patients were used for validation. The PDRPSP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy. Results A PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in “de-novo” PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRPIT, PDRPNL, and PDRPSP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA.

FPGA System-on-Chips (SoCs) are heterogeneous platforms that combine general-purpose processors with a field-programmable gate array (FPGA) fabric. The FPGA fabric is composed of a programmable logic in which hardware accelerators can be deployed to accelerate the execution of specific functionality. The main source of unpredictability when bounding the execution times of hardware accelerators pertains the access to the shared memories via the on-chip bus. This work is focused on bounding the worst-case bus contention experienced by the hardware accelerators deployed in the FPGA fabric. To this end, this work considers the AMBA AXI bus, which is the de-facto standard communication interface used in most the commercial off-the-shelf (COTS) FPGA SoCs, and presents an analysis technique to bound the response times of hardware accelerators implemented on such platforms. A fine-grained modeling of the AXI bus and AXI interconnects is first provided. Then, contention delays are studied under hierarchical bus infrastructures with arbitrary depths. Experimental results are finally presented to validate the proposed model with execution traces on two modern FPGA-based SoC produced by Xilinx (Zynq-7000 and Zynq-Ultrascale+ families) and to assess the performance of the proposed analysis.

A narrow upper Paleozoic belt crops out in the northern tip of Sierra de Tecka through the Quebrada de Güera-Peña (Patagonia, Argentina). There, black shales of the Pampa de Tepuel Formation contain marine fossil invertebrates previously listed as belonging to the “Levipustula” fauna. Material recently recorded by the authors comprises, in order of abundance, gastropods [Glabrocingulum (Glabrocingulum) poperimense (Maxwell), G. (Stenozone) argentinum (Reed), G. (Stenozone) sp., Peruvispira teckaensis sp. nov., Ananias riccardii Pinilla], bivalves [Nuculopsis (Nuculopsis) patagoniensis González, Phestia tepuelensis González, Streblochondria sueroi González, Streblopteria sp.], conulariids [Paraconularia cf. ugartei Cúneo and Sabattini], brachiopods [Amosia sueroi Simanauskas, Languigneotus laevicaudatum (Amos), Beecheria patagonica Amos], trilobites [Australosutura argentinensis Hahn and Hahn], cephalopods [Pseudoorthoceratidae Flower and Caster, Sueroceras? sp., Mitorthoceras? sp.], and rugose corals [?Lophophyllidiidae Moore and Jeffords]. In addition, the present study includes the new key brachiopods Languigneotus dammanorum gen. et sp. nov. and Tuberculatella waterhousei sp. nov. from younger localities of the Tepuel-Genoa Basin. The Languigneotus laevicaudatum and Languigneotus-Verchojania subzones (late Pennsylvanian) are proposed herein to replace the former Tuberculatella Zone. In addition, previous stratigraphic relationships and correlations of the study section with the Arroyo Pescado (Estancia Ap Iwan) and Esquel areas are discussed. The general stratigraphic profile of a glacial-related section cropping out at Estancia Ap Iwan includes lower conglomeradic beds, which are reinterpreted as early Jurassic in age, and glacimarine levels that are partially equivalent to the Pampa de Tepuel Formation but older than those of Quebrada de Güera-Peña. A correlation of the Esquel Formation with the Arroyo Pescado Formation and other contemporaneous units on the paleopacific margin is assessed, implying that the Esquel Formation should be segregated from the Tepuel Group. The Esquel and Arroyo Pescado formations can be regarded as the basement of the glaciomarine column of the Tepuel-Genoa Basin.

A narrow upper Paleozoic belt crops out in the northern tip of Sierra de Tecka through the Quebrada de Güera-Peña (Patagonia, Argentina). There, black shales of the Pampa de Tepuel Formation contain marine fossil invertebrates previously listed as belonging to the “Levipustula” fauna. Material recently recorded by the authors comprises, in order of abundance, gastropods [Glabrocingulum (Glabrocingulum) poperimense (Maxwell), G. (Stenozone) argentinum (Reed), G. (Stenozone) sp., Peruvispira teckaensis sp. nov., Ananias riccardii Pinilla], bivalves [Nuculopsis (Nuculopsis) patagoniensis González, Phestia tepuelensis González, Streblochondria sueroi González, Streblopteria sp.], conulariids [Paraconularia cf. ugartei Cúneo and Sabattini], brachiopods [Amosia sueroi Simanauskas, Languigneotus laevicaudatum (Amos), Beecheria patagonica Amos], trilobites [Australosutura argentinensis Hahn and Hahn], cephalopods [Pseudoorthoceratidae Flower and Caster, Sueroceras? sp., Mitorthoceras? sp.], and rugose corals [?Lophophyllidiidae Moore and Jeffords]. In addition, the present study includes the new key brachiopods Languigneotus dammanorum gen. et sp. nov. and Tuberculatella waterhousei sp. nov. from younger localities of the Tepuel-Genoa Basin. The Languigneotus laevicaudatum and Languigneotus-Verchojania subzones (late Pennsylvanian) are proposed herein to replace the former Tuberculatella Zone. In addition, previous stratigraphic relationships and correlations of the study section with the Arroyo Pescado (Estancia Ap Iwan) and Esquel areas are discussed. The general stratigraphic profile of a glacial-related section cropping out at Estancia Ap Iwan includes lower conglomeradic beds, which are reinterpreted as early Jurassic in age, and glacimarine levels that are partially equivalent to the Pampa de Tepuel Formation but older than those of Quebrada de Güera-Peña. A correlation of the Esquel Formation with the Arroyo Pescado Formation and other contemporaneous units on the paleopacific margin is assessed, implying that the Esquel Formation should be segregated from the Tepuel Group. The Esquel and Arroyo Pescado formations can be regarded as the basement of the glaciomarine column of the Tepuel-Genoa Basin. RESUMEN Una estrecha faja neopaleozoica aflora atravesando el extremo norte de la Sierra de Tecka a lo largo de la Quebrada de Güera-Peña (Patagonia, Argentina). Alli, lutitas negras de la Formación Pampa de Tepuel contienen invertebrados marinos previamente asignados a la fauna de “Levipustula”. Nuevo material coleccionado por los autores incluye, en orden de abundancia, gastrópodos [Glabrocingulum (Glabrocingulum) poperimense (Maxwell), G. (Stenozone) argentinum (Reed), G. (Stenozone) sp., Peruvispira teckaensis sp. nov., Ananias riccardii Pinilla], bivalvos [Nuculopsis (Nuculopsis) patagoniensis González, Phestia tepuelensis González, Streblochondria sueroi González, Streblopteria sp.], conuláridos [Paraconularia cf. ugartei Cúneo y Sabattini], braquiópodos [Amosia sueroi Simanauskas, Languigneotus laevicaudatum (Amos), Beecheria patagonica Amos], trilobites [Australosutura argentinensis Hahn y Hahn], cefalópodos [Pseudoorthoceratidae Flower y Caster, Sueroceras? sp., Mitorthoceras? sp.] y corales rugosos [?Lophophyllidiidae Moore y Jeffords]. El presente estudio incluye además los nuevos braquiópodos clave Languigneotus dammanorum gen. et sp. nov. y Tuberculatella waterhousei sp. nov. provenientes de otras localidades más jóvenes de la cuenca. Se proponen formalmente las subzonas de Languigneotus laevicaudatum y de Languigneotus-Verchojania, en reemplazo de la anteriormente equivalente Zona de Tuberculatella. Se discuten las relaciones estratigráficas y correlaciones previamente propuestas para la sección estudiada en relación a las áreas de Arroyo Pescado (Estancia Ap Iwan) y Esquel. El perfil estratigráfico general de la sección con influencia glacial aflorante en la Estancia Ap Iwan incluye una parte inferior con conglomerados que son reasignados al Jurásico inferior, y tramos superiores que son parcialmente equivalentes a la Formación Pampa de Tepuel pero más antiguos que los aflorantes en la Quebrada de Güera Peña. Por otro lado, se refuerza la correlación de la Formación Arroyo Pescado con la Formación Esquel, así como con otras unidades contemporáneas reconocidas hacia el oeste, sobre el margen paleopacífico. La correlación de las formaciones Esquel y Arroyo Pescado implica segregar la primera del Grupo Tepuel, así como considerar a las mismas como basamento de la columna estratigráfica de la Cuenca de Tepuel-Genoa.

Earth system sensitivity (ESS) is the long-term (>103 yr) equilibrium temperature response to doubled CO2. ESS has climate policy implications because global temperatures are not expected to decline appreciably for at least 103 yr, even if anthropogenic greenhouse-gas emissions drop to zero. We report quantitative ESS estimates of 3 °C or higher for much of the Cretaceous and early Paleogene based on paleo-reconstructions of CO2 and temperature. These estimates are generally higher than climate sensitivities simulated from global climate models for the same ancient periods (~3 °C). We conclude that climate models do not capture the full suite of positive climate feedbacks during greenhouse worlds. These absent feedbacks are probably related to clouds, trace greenhouse gases, seasonal snow cover, and/or vegetation, especially in polar regions. Continued warming in the coming decades as anthropogenic greenhouse gases accumulate in the atmosphere ensures that characterizing and quantifying these positive climate feedbacks will become a scientific challenge of increasing priority.

Rationale: Idiopathic REM sleep behavior disorder (iRBD) is considered a prodromal stage of Parkinson's disease (PD) and other Lewy-body disorders. Spatial covariance analysis of [18F]-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) data has disclosed a specific brain pattern of altered glucose metabolism in PD. In this study, we identify the metabolic pattern underlying iRBD and compare it to the known PD pattern. To understand the relevance of the iRBD pattern to disease progression, we study the expression of the iRBD pattern in de novo PD patients.Methods:The iRBD-related pattern was identified in18F-FDG-PET scans of 21 patients with polysomnographically-confirmed iRBD and 19 controls using spatial covariance analysis. Expression of the iRBD-related pattern was subsequently computed in18F-FDG-PET scans of 44 controls and 38 de novo, treatment-naïve PD patients. Of these 38 PD patients, 24 had probable RBD according to the Mayo Sleep Questionnaire. Neuropsychological evaluation showed mild cognitive impairment in 20 PD patients (PD-MCI), of whom sixteen also had concomitant RBD and roughly half (11/20) had bilateral motor symptoms.Results:The iRBD-related pattern was characterized by relative hypermetabolism in cerebellum, brainstem, thalamus, sensorimotor cortex, and hippocampus, and by relative hypometabolism in middle cingulate, temporal, occipital and parietal cortices. This topography partially overlapped with the PD-related pattern (PDRP). The iRBD-related pattern was significantly expressed in PD patients compared to controls (P

Made available in DSpace on 2018-08-02T00:03:16Z (GMT). No. of bitstreams: 1 tese_9802_Matheus Darós Pagani.pdf: 6066729 bytes, checksum: dd4fc65fed982018015efa9e885a82cb (MD5) Previous issue date: 2016-05-02 Colunas isoladas são comumente utilizadas em poços de petróleo que utilizam processos de recuperação avançada de óleo por injeção de vapor para diminuir as perdas de calor durante o transporte do fluido injetado na formação. Esta dissertação apresenta e desenvolve uma abordagem computacional para simular as condições de produção e recuperação de óleo nesses poços, bem como maneiras de se aplicar essa abordagem para simular casos de transporte de calor e massa e determinar a eficiência energética e econômica do uso de isolamento térmico nesses processos de recuperação e produção. Palavras chave: Injeção de Vapor; EOR; Volumes Finitos; Isolamento Térmico; Análise Termoeconomica

The assessment of the degree of order of brainmetabolism bymeans of a statisticalmechanistic approach applied to FDG-PET, allowed us to characterize healthy subjects as well as patients with mild cognitive impairment and Alzheimer's Disease (AD). The intensity signals from 24 volumes of interest were submitted to principal component analysis (PCA) giving rise to a major first principal component whose eigenvalue was a reliable cumulative index of order. This index linearly decreased from 77 to 44% going from normal aging to AD patients with intermediate conditions between these values (r =0.96, p b 0.001). Bootstrap analysis confirmed the statistical significance of the results. The progressive detachment of different brain regions from the first component was assessed, allowing for a purely data driven reconstruction of already known maximally affected areas. Wedemonstrated for the first time the reliability of a single global index of order in discriminating groups of cognitively impaired patients with different clinical outcome. The second relevant finding was the identification of clusters of regions relevant to AD pathology progressively separating fromthe first principal component through different stages of cognitive impairment, including patients cognitively impaired but not converted to AD. This paved the way to the quantitative assessment of the functional networking status in individual patients.

In the recent years, several studies have highlighted how psychological trauma can cause anatomical and functional changes in specific brain areas associated with the onset of post-traumatic symptoms. Thanks to the development of neuroimaging techniques such as Magnetic Resonance Imaging (MRI), functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), it was possible to identify the brain circuits involved in the pathophysiology of Post-traumatic Stress Disorder (PTSD). Several studies have shown that 5 to 35% of patients with cancer might suffer from post-traumatic symptoms related to their disease (Kangas et al., 2002; National Cancer Institute, 2012).

The vulnerability of urban infrastructure to both ground shaking and geotechnical failure during large earthquakes has been demonstrated by recent earthquakes such as the 2010 - 2011 Canterbury earthquake sequence (New Zealand, 2010 - 2011) or 2010 Haiti event. Probabilistic seismic risk analysis to infrastructure systems requires the characterisation of both the transient shaking and permanent ground deformation elements of the hazard, and must do so incorporating both the aleatory and epistemic uncertainties and the spatial correlations and dependencies that are inherent in both of these aspects. Recent developments in characterisation of spatial correlation and cross-correlation in the ground motion uncertainties form the foundations of a comprehensive Monte Carlo-based methodology for analysis of seismic risk to spatially extended systems. New research directions are needed, however, in order to ensure that secondary hazard aspects are incorporated in the same way. These include the treatment of site amplification of the ground shaking, the modelling of permanent ground deformation from slope displacement and liquefaction, and permanent displacement due to coseismic slip on and around the fault rupture. Key considerations for integrated probabilistic framework for physically-realistic characterisation of the ground shaking and permanent ground displacement are illustrated using the example of simulation spatially correlated fault slip on an active fault rupture in a manner that can be integrated within a Monte Carlo-based probabilistic seismic hazard methodology.

Since the introduction of the first systems in 2001, the field of clinical PET/CT has experienced impressive growth in terms of system design and functionality, supportive software solutions and the availability and range of clinically approved PET tracers. Developments were initially directed towards the creation of solutions for implementation primarily in systemic oncology, rather than in brain studies. Over the intervening years, however, clinical brain PET imaging has benefitted tremendously through the use of available equipment and organisation. The number of clinical brain PET scans at a clinical site might not initially be sufficient to justify the acquisition of a PET/CT scanner, but as a supplementary element in a production line dominated by oncology, brain PET studies can play a very significant role.

The aim of the present study was to investigate brain glucose metabolism in patients with Hodgkin disease (HD) after diagnosis and during chemotherapy treatment. Following the administration of first-line doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy, 74 HD patients underwent 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography brain scans, both baseline (PET0) and interim (PET2) at the Department of Biomedicine and Prevention, University of Rome Tor Vergata (Rome, Italy). Fifty-seven patients were further evaluated 15±6 days after four additional cycles (PET6). Furthermore, a control group (CG) of 40 chemotherapy-naïve subjects was enrolled. Differences in brain 18F-FDG uptake between the CG, PET0, PET2 and PET6 scans were analyzed using statistical parametric mapping. Compared with the PET0 and CG scans, the PET2 scan demonstrated a higher metabolic activity in Brodmann area (BA) 39, and a metabolic reduction in BA 11 bilaterally and in left BA 32. All of these changes disappeared at PET6. The results of the present study indicate that ABVD chemotherapy has a limited impact on brain metabolism.