80 research outputs found

    A parallel interaction potential approach coupled with the immersed boundary method for fully resolved simulations of deformable interfaces and membranes

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    In this paper we show and discuss the use of a versatile interaction potential approach coupled with an immersed boundary method to simulate a variety of flows involving deformable bodies. In particular, we focus on two kinds of problems, namely (i) deformation of liquid-liquid interfaces and (ii) flow in the left ventricle of the heart with either a mechanical or a natural valve. Both examples have in common the two-way interaction of the flow with a deformable interface or a membrane. The interaction potential approach (de Tullio & Pascazio, Jou. Comp. Phys., 2016; Tanaka, Wada and Nakamura, Computational Biomechanics, 2016) with minor modifications can be used to capture the deformation dynamics in both classes of problems. We show that the approach can be used to replicate the deformation dynamics of liquid-liquid interfaces through the use of ad-hoc elastic constants. The results from our simulations agree very well with previous studies on the deformation of drops in standard flow configurations such as deforming drop in a shear flow or a cross flow. We show that the same potential approach can also be used to study the flow in the left ventricle of the heart. The flow imposed into the ventricle interacts dynamically with the mitral valve (mechanical or natural) and the ventricle which are simulated using the same model. Results from these simulations are compared with ad- hoc in-house experimental measurements. Finally, a parallelisation scheme is presented, as parallelisation is unavoidable when studying large scale problems involving several thousands of simultaneously deforming bodies on hundreds of distributed memory computing processors

    Manipulating the alpha level cannot cure significance testing

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    We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable

    Follow My Eyes: The Gaze of Politicians Reflexively Captures the Gaze of Ingroup Voters

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    Studies in human and non-human primates indicate that basic socio-cognitive operations are inherently linked to the power of gaze in capturing reflexively the attention of an observer. Although monkey studies indicate that the automatic tendency to follow the gaze of a conspecific is modulated by the leader-follower social status, evidence for such effects in humans is meager. Here, we used a gaze following paradigm where the directional gaze of right- or left-wing Italian political characters could influence the oculomotor behavior of ingroup or outgroup voters. We show that the gaze of Berlusconi, the right-wing leader currently dominating the Italian political landscape, potentiates and inhibits gaze following behavior in ingroup and outgroup voters, respectively. Importantly, the higher the perceived similarity in personality traits between voters and Berlusconi, the stronger the gaze interference effect. Thus, higher-order social variables such as political leadership and affiliation prepotently affect reflexive shifts of attention

    The Italian Draft Law on the \u2018Provisions Concerning the Safeguarding of the Intangible Cultural Heritage\u2019

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    Intangible cultural heritage in Italy is still in need of a unified approach, capable of providing reliable criteria for identifying its assets and for indicating timescales and means by which they should be safeguarded. In the continued absence of up-to-date, ad hoc state legislation (since the content of those laws which do implement international Conventions is too generic in nature to be sufficiently effective), the Regions have proceeded to act in a somewhat scattered manner, giving rise to an extremely fragmented and very disorderly regulatory framework. The draft law N. 4486, "Provisions Concerning the Safeguarding of the Intangible Cultural Heritage", presented on 12th May 2017 at the Chamber of Deputies of the Italian Republic - as the result of the work of an interdisciplinary and inter-university research team coordinated by Marco Giampieretti, who has drafted the final text with the collaboration of Simona Pinton - seeks to fill the serious void that exists in Italian legal system by aligning it to the principles of international and European law, by redirecting the relevant State and Regional legislation, and by satisfying the fundamental requirements of the national community

    Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. Update December 2014

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    Changes in social norms during the early stages of the COVID-19 pandemic across 43 countries

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    The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

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    The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFőĪ production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28¬†days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p¬†=¬†0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-őĪ: tumor necrosis factor

    The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS)

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    Objective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.</p

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

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    To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer
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