h-multigrid agglomeration based solution strategies for discontinuous Galerkin discretizations of incompressible flow problems

In this work we exploit agglomeration based $h$-multigrid preconditioners to speed-up the iterative solution of discontinuous Galerkin discretizations of the Stokes and Navier-Stokes equations. As a distinctive feature $h$-coarsened mesh sequences are generated by recursive agglomeration of a fine grid, admitting arbitrarily unstructured grids of complex domains, and agglomeration based discontinuous Galerkin discretizations are employed to deal with agglomerated elements of coarse levels. Both the expense of building coarse grid operators and the performance of the resulting multigrid iteration are investigated. For the sake of efficiency coarse grid operators are inherited through element-by-element $L^2$ projections, avoiding the cost of numerical integration over agglomerated elements. Specific care is devoted to the projection of viscous terms discretized by means of the BR2 dG method. We demonstrate that enforcing the correct amount of stabilization on coarse grids levels is mandatory for achieving uniform convergence with respect to the number of levels. The numerical solution of steady and unsteady, linear and non-linear problems is considered tackling challenging 2D test cases and 3D real life computations on parallel architectures. Significant execution time gains are documented.Comment: 78 pages, 7 figure

A Hybrid High-Order method for multiple-network poroelasticity

We develop Hybrid High-Order methods for multiple-network poroelasticity, modelling seepage through deformable fissured porous media. The proposed methods are designed to support general polygonal and polyhedral elements. This is a crucial feature in geological modelling, where the need for general elements arises, e.g., due to the presence of fracture and faults, to the onset of degenerate elements to account for compaction or erosion, or when nonconforming mesh adaptation is performed. We use as a starting point a mixed weak formulation where an additional total pressure variable is added, that ensures the fulfilment of a discrete inf-sup condition. A complete theoretical analysis is performed, and the theoretical results are demonstrated on a complete panel of numerical tests

An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine

Cytosolic phosphorylated EGFR is predictive of recurrence in early stage penile cancer patients: A retropective study

Background: Penile cancer (PC) is a rare tumor, and therapeutic options are limited for this disease, with an overall 5-year overall survival around 65-70%. Adjuvant therapy is not recommended for patients with N0-1 disease, despite up to 60% of these patients will die within 5 years from diagnosis. Methods: Medical records of all patients who underwent radical surgery at University Federico II of Naples and at National Tumor Institute "Pascale" of Naples for early squamous cell carcinoma of the penis from January, 2000 to December, 2011 were retrieved. Paraffin wax embedded tissue specimens were retrieved from the pathology archives of the participating Institutions for all patients. Expression of p-EGFR, EGFR and positivity to HPV were evaluated along with other histological variables of interest. Demographic data of eligible patients were retrieved along with clinical characteristics such as type of surgical operation, time of follow up, time of recurrence, overall survival. A multivariable model was constructed using a forward stepwise selection procedure. Results: Thirty eligible patients were identified. All patients were positive for EGFR by immunohistochemistry, while 13 and 16 were respectively positive for nuclear and cytosolic p-EGFR. No EGFR amplification was detected by FISH. Eight patients were positive for high-risk HPV by ISH. On univariable analysis, corpora cavernosa infiltration (OR 7.8; 95% CI = 0,8 to 75,6; P = 0,039) and positivity for cytosolic p-EGFR (OR 7.6; 95% CI = 1.49 to 50; P = 0.009) were predictive for recurrence, while only positivity for cytosolic p-EGFR (HR = 9.0; 95% CI 1.0-100; P = 0,0116) was prognostic for poor survival. Conclusion: It is of primary importance to identify patients with N0-1 disease who are at increased risk of recurrence, as they do not normally receive any adjuvant therapy. Expression of p-EGFR was found in this series to be strongly related to increase risk of recurrence and shorter overall survival. This finding is consistent with the role of p-EGFR in other solid malignancies. Integration of p-EGFR with classic prognostic factors and other histology markers should be pursued to establish optimal adjuvant therapy for N0-1 PC patients

A pandemic strain of calicivirus threatens rabbit industries in the Americas

Rabbit Hemorrhagic Disease (RHD) is a severe acute viral disease specifically affecting the European rabbit Oryctolagus cuniculus. As the European rabbit is the predominant species of domestic rabbit throughout the world, RHD contributes towards significant losses to rabbit farming industries and endangers wild populations of rabbits in Europe and other predatory animals in Europe that depend upon rabbits as a food source. Rabbit Hemorrhagic Disease virus (RHDV) – a Lagovirus belonging to the family Caliciviridae is the etiological agent of RHD. Typically, RHD presents with sudden death in 70% to 95% of infected animals. There have been four separate incursions of RHDV in the USA, the most recent of which occurred in the state of Indiana in June of 2005. Animal inoculation studies confirmed the pathogenicity of the Indiana 2005 isolate, which caused acute death and pathological changes characterized by acute diffuse severe liver necrosis and pulmonary hemorrhages. Complete viral genome sequences of all USA outbreak isolates were determined and comparative genomics revealed that each outbreak was the result of a separate introduction of virus rather than from a single virus lineage. All of the USA isolates clustered with RHDV genomes from China, and phylogenetic analysis of the major capsid protein (VP60) revealed that they were related to a pandemic antigenic variant strain known as RHDVa. Rapid spread of the RHDVa pandemic suggests a selective advantage for this new subtype. Given its rapid spread, pathogenic nature, and potential to further evolve, possibly broadening its host range to include other genera native to the Americas, RHDVa should be regarded as a threat

Veno-occlusive disease nurse management: Development of a dynamic monitoring tool by the GITMO nursing group

Veno-occlusive disease (VOD) is a complication arising from the toxicity of conditioning regimens that have a significant impact on the survival of patients who undergo stem cell transplantation. There are several known risk factors for developing VOD and their assessment before the start of conditioning regimens could improve the quality of care. Equally important are early identification of signs and symptoms ascribable to VOD, rapid diagnosis, and timely adjustment of support therapy and treatment. Nurses have a fundamental role at the stages of assessment and monitoring for signs and symptoms; therefore, they should have documented skills and training. The literature defines nurses' areas of competence in managing VOD, but in the actual clinical practice, this is not so clear. Moreover, there is an intrinsic difficulty in managing VOD due to its rapid and often dramatic evolution, together with a lack of care tools to guide nurses. Through a complex evidence-based process, the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), cellule staminali emopoietiche e terapia cellulare nursing board has developed an operational flowchart and a dynamic monitoring tool applicable to haematopoietic stem cell transplantation patients, whether they develop this complication or not

PI3Kδ Inhibition as a Potential Therapeutic Target in COVID-19

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Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations in Mixed Lung Adenocarcinoma

BACKGROUND: Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be 'major', characterized by a single tumor showing two different histologic types, and 'minor', due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas. METHODS: 590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR. RESULTS: 10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components. CONCLUSION: Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research