Sensitivity Analysis in Poro-Elastic and Poro-Visco-Elastic Models with Respect to Boundary Data

In this article we consider poro-elastic and poro-visco-elastic models inspired by problems in medicine and biology, and we perform sensitivity analysis on the solutions of these fluid-solid mixture problems with respect to the imposed boundary data, which are the main drivers of the system. Moreover, we compare the results obtained in the elastic case vs. visco-elastic case, as it is known that structural viscosity of biological tissues decreases with age and disease. Sensitivity analysis is the first step towards optimization and control problems associated with these models, which is our ultimate goal

Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight

Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: Results from a systematic literature review and a network meta-analysis

Background: The objective of this study was to estimate the relative efficacy and safety of targeted therapies for the treatment of metastatic melanoma using a network meta-analysis (NMA). Methods: A systematic literature review (SLR) identified studies in Medline, Embase and Cochrane published until November 2020. Screening used prespecified eligibility criteria. Following a transitivity assessment across included studies, Bayesian NMA was conducted. Results: A total of 43 publications reporting 15 targeted therapy trials and 42 reporting 18 immunotherapy trials were retained from the SLR and considered for the NMA. Due to substantial between-study heterogeneity with immunotherapy trials, the analysis considered a network restricted to targeted therapies. Among combination therapies, encorafenib + binimetinib was superior to dabrafenib + trametinib for overall response rate (OR = 1.86; 95 % credible interval [CrI] 1.10, 3.17), superior to vemurafenib + cobimetinib with fewer serious adverse events (SAEs) (OR = 0.51; 95 % CrI 0.29, 0.91) and fewer discontinuations due to AEs (OR = 0.45; 95 % CrI 0.21, 0.96), and superior to atezolizumab + vemurafenib + cobimetinib with fewer SAEs (OR = 0.41; 95 % CrI 0.21, 0.82). Atezolizumab + vemurafenib + cobimetinib and encorafenib + binimetinib were generally comparable for efficacy endpoints. Among double combination therapies, encorafenib + binimetinib showed high probabilities of being better for all efficacy and safety endpoints. Conclusions: This NMA confirms that combination therapies are more efficacious than monotherapies. Encorafenib + binimetinib has a favourable efficacy profile compared to other double combination therapies and a favourable safety profile compared to both double and triple combination therapies

NELLA SPIRALE DEL CLIMA culture e società mediterranee di fronte ai cambiamenti climatici

Il clima è sempre cambiato e i mutamenti hanno causato danni e rischi non previsti, che hanno richiesto nuovi adattamenti e risposte adeguate sul piano sociale, culturale ed economico. Gli autori, coadiuvati da un gruppo di ricercatori, hanno esplorato la storia degli ultimi tre millenni delle civiltà mediterranee, presentando un excursus divulgativo, basato su autorevoli studi scientifici e storici. Lo scopo è di delineare in modo complessivo non solo l’andamento dei mutamenti climatici e le loro ripercussioni sociali, ma anche le idee e le teorie sul clima, dai filosofi dell’antica Grecia, agli scrittori latini, agli enciclopedisti medievali, cristiani e arabi, fino al pensiero di età moderna, all’illuminismo e al positivismo ottocentesco. Le previsioni del tempo, il clima e la salute, il rapporto fra clima e ambiente sono temi presenti in tutte le civiltà mediterranee antiche e recenti: su questi temi le culture hanno sempre elaborato interpretazioni e risposte. Questo “viaggio” nel passato, che mette in luce una storia inedita e in gran parte da esplorare, giunge fino all’attuale riscaldamento globale. Questa nuova sfida è meglio valutabile in una prospettiva di “mutamento climatico storico”, a cui l’azione antropica sta aggiungendo un formidabile acceleratore

Melanoma metastasis mimicking gastric cancer: a challenge that starts from diagnosis

The gastrointestinal tract is an uncommon site of metastasis in melanoma. However, when the primary melanoma cannot be found, the diagnosis of gastric melanoma by endoscopic biopsy is problematic mainly because some tumors are amelanotic and do not contain melanin granules detectable by microscopy. A 56-year-old Caucasian man with melanoma was referred to us following an initial histopathological diagnosis via gastroscopy of poorly differentiated primary gastric carcinoma. A computerized tomography (CT) scan showed metastatic disease and on the basis of this information we started palliative chemotherapy. However, the atypical presentation of the disease with subcutaneous metastases prompted us to make a more in-depth evaluation. Immunohistochemical evaluation modified the diagnosis to melanoma. After only one cycle of chemotherapy, treatment was changed to dabrafenib + trametinib, which was better tolerated and initially induced a partial response. The patient is currently in good clinical condition 20 months after diagnosis. Our case report highlights the difficulty in diagnosing melanoma of the gastrointestinal tract and indicates the need for pathologists and clinicians to consider such a possibility when they are faced with a diagnosis of poorly differentiated gastric cancer and unusual sites of metastasis

Case study exemplar of detecting severe diastolic dysfunction using ballistocardiogram

The specific aim of this case study was to describe how monitoring ballistocardiogram (BCG) waveforms can detect early heart failure (HF) changes. HF significantly impairs quality of life and is the principal cause for hospital readmissions in older adults. HF prevalence in American adults aged 65 years and older is expected to increase over 70% by 2030. Detecting worsening HF is challenging. Invasive arterial waveforms display blood pressure changes with each heartbeat; BCG waveforms display repetitive body motions resulting from ejection of blood into the great vessels. BCG waveforms change as cardiac function changes. Currently, BCG signals can be captured non-invasively using sensors placed under a bed mattress and provide heart and respiratory rates. We have developed a new way to analyze the BCG waveform using an innovative closed-loop physiological model of the cardiovascular system. The subject, a 94-year old female with hypertension, presented to her physician with symptoms associated with a new diagnosis of acute mixed congestive HF. Mean heart and respiratory rate trends obtained from her bed sensor in the prior two months did not indicate HF. We simulated cardiac cycles using normal cardiac function data, mildly impaired diastolic function data, and the subject’s echocardiography data. The results demonstrated BCG waveform changes that correlated with decreasing cardiac output related to worsening diastolic function. New methods for clinically interpreting BCG waveforms present a significant opportunity for improving early HF detection and improving outcomes. Working on a clinical problem from an engineering perspective merges two disciplines, creating a new methodology

Existence of global strong solutions to a beam-fluid interaction system

We study an unsteady non linear fluid-structure interaction problem which is a simplified model to describe blood flow through viscoleastic arteries. We consider a Newtonian incompressible two-dimensional flow described by the Navier-Stokes equations set in an unknown domain depending on the displacement of a structure, which itself satisfies a linear viscoelastic beam equation. The fluid and the structure are fully coupled via interface conditions prescribing the continuity of the velocities at the fluid-structure interface and the action-reaction principle. We prove that strong solutions to this problem are global-in-time. We obtain in particular that contact between the viscoleastic wall and the bottom of the fluid cavity does not occur in finite time. To our knowledge, this is the first occurrence of a no-contact result, but also of existence of strong solutions globally in time, in the frame of interactions between a viscous fluid and a deformable structure

Toward polarized antiprotons: Machine development for spin-filtering experiments

The paper describes the commissioning of the experimental equipment and the machine studies required for the first spin-filtering experiment with protons at a beam kinetic energy of $49.3\,$MeV in COSY. The implementation of a low-$\beta$ insertion made it possible to achieve beam lifetimes of $\tau_{\rm{b}}=8000\,$s in the presence of a dense polarized hydrogen storage-cell target of areal density $d_{\rm t}=(5.5\pm 0.2)\times 10^{13}\,\mathrm{atoms/cm^{2}}$. The developed techniques can be directly applied to antiproton machines and allow for the determination of the spin-dependent $\bar{p}p$ cross sections via spin filtering