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Moving masses are of interest in many applications of structural dynamics, soliciting in the last decades a vast debate in the scientific literature. However, despite the attention devoted to the subject, to the best of the authors’ knowledge, there is a lack of analysis about the fate of a movable mass when it rolls or slips with friction on a structure. With the aim of elucidating the dynamics of the simplest paradigm of this system and to investigate its asymptotic response, we make reference to a two-degree-of-freedom model made of an elastically vibrating carriage surmounted by a spherical mass, facing the problem both theoretically and experimentally. In case of linear systems, the analytical solutions and the laboratory tests performed on ad hoc constructed prototypes highlighted a counterintuitive asymptotic dynamics, here called binary: in the absence of friction at the interface of the bodies’ system, the mass holds its initial position or, if nonzero damping acts, at the end of the motion it is in a position that exactly recovers the initial relative distance carriage–sphere. While the first result might be somewhat obvious, the second appears rather surprising. Such a binary behaviour is also confirmed for a Duffing-like system, equipped with cubic springs, while it can be lost when non-smooth friction phenomena occur, as well as in the case of elastic springs restraining the motion of the sphere. The obtained analytical results and the numerical findings, also confirmed by experimental evidences, contribute to the basic understanding of the role played by the damping parameters governing the systems’ dynamics with respect to its asymptotic behaviour and could pave the way for designing active or passive vibration controllers of interest in engineering.

Purpose To describe reoperations in the operating room for complications that occurred within the first 90 days after gel stent implantation or trabeculectomy at a single institution over 5 years. Methods In this retrospective chart review, patients who have undergone gel stent implantation with mitomycin C (MMC) or trabeculectomy with MMC were enrolled. Postoperative complications that required reoperations within the first 90 days were evaluated. Results A total of 510 surgeries were performed on 392 patients over a 57-month period by 2 glaucoma surgeons. Of these, 284 were gel stent implantation, and 226 were trabeculectomy. Combined phacoemulsification was performed in 52/284 (18.3%) in the gel stent group and in 26/226 (11.5%) of eyes in the trabeculectomy group (p = 0.03). Reoperations took place in 13/510 (2.5%) eyes, including 4/284 (1.4%) in the gel stent group, 9/226 (4.0%) in the trabeculectomy group (p = 0.07). In the gel stent group, indications for reoperation were bleb failure (2), suprachoroidal hemorrhage (1), bullous keratopathy (1). In the trabeculectomy group, indications for reoperation were bleb failure (3), overfiltration (2), persistent wound leak (2), aqueous misdirection (2). Conclusions The rates of reoperation for early postoperative complications after gel stent or trabeculectomy was low and comparable with previous studies. A slightly higher number of reoperations within 90 days was observed in the trabeculectomy group than the gel stent group despite the more significant number of combined procedures in the latter group. Bleb failure was the most common indications for reoperation in both groups. Excessive outflow was a cause of reoperation mostly in the trabeculectomy group.

We described nailfold videocapillaroscopy (NVC) findings and estimated the prevalence of serum anti-nuclear (ANA) and extractable nuclear antigen autoantibodies (ENA) in a cohort of sarcoidosis patients, comparing them with adequate healthy controls (HCs) and with primary Raynaud’s phenomenon patients (PRPs). NVC findings were also correlated with the occurrence of autoantibodies, current treatment, laboratory parameters, variables of lung function and whole-body imaging data. Twenty-six patients with sarcoidosis were assessed through NVC, laboratory parameters, pulmonary function tests, chest-X ray and 18- fluorodeoxyglucose positron emission tomography/computed tomography. The NVC parameters and ANA/ENA dosage were recorded also in 30 PRPs and 30 HCs. Sarcoidosis patients showed a higher rate of capillary dilations and nonspecific abnormalities and a lower mean capillary absolute number than PRPs and HCs (p p p

Background and purpose While HCC is an inflammation-associated cancer, CRLM develops on permissive healthy liver microenvironment. To evaluate the immune aspects of these two different environments, peripheral blood-(PB), peritumoral-(PT) and tumoral tissues-(TT) from HCC and CRLM patients were evaluated. Methods 40 HCC and 34 CRLM were enrolled and freshly TT, PT and PB were collected at the surgery. PB-, PT- and TT-derived CD4+CD25+ Tregs, M/PMN-MDSC and PB-derived CD4+CD25− T-effector cells (Teffs) were isolated and characterized. Tregs’ function was also evaluated in the presence of the CXCR4 inhibitor, peptide-R29, AMD3100 or anti-PD1. RNA was extracted from PB/PT/TT tissues and tested for FOXP3, CXCL12, CXCR4, CCL5, IL-15, CXCL5, Arg-1, N-cad, Vim, CXCL8, TGFβ and VEGF-A expression. Results In HCC/CRLM-PB, higher number of functional Tregs, CD4+CD25hiFOXP3+ was detected, although PB-HCC Tregs exert a more suppressive function as compared to CRLM Tregs. In HCC/CRLM-TT, Tregs were highly represented with activated/ENTPD-1+Tregs prevalent in HCC. As compared to CRLM, HCC overexpressed CXCR4 and N-cadherin/vimentin in a contest rich in arginase and CCL5. Monocytic MDSCs were highly represented in HCC/CRLM, while high polymorphonuclear MDSCs were detected only in HCC. Interestingly, the function of CXCR4-PB-Tregs was impaired in HCC/CRLM by the CXCR4 inhibitor R29. Conclusion In HCC and CRLM, peripheral blood, peritumoral and tumoral tissues Tregs are highly represented and functional. Nevertheless, HCC displays a more immunosuppressive TME due to Tregs, MDSCs, intrinsic tumor features (CXCR4, CCL5, arginase) and the contest in which it develops. As CXCR4 is overexpressed in HCC/CRLM tumor/TME cells, CXCR4 inhibitors may be considered for double hit therapy in liver cancer patients.

Abstract Poromechanics plays a key role in modelling hard and soft tissue behaviours, by providing a thermodynamic framework in which chemo-mechanical mutual interactions among fluid and solid constituents can be consistently rooted, at different scale levels. In this context, how different biological species (including cells, extra-cellular components and chemical metabolites) interplay within complex environments is studied for characterizing the mechanobiology of tumor growth, governed by intratumoral residual stresses that initiate mechanotransductive processes deregulating normal tissue homeostasis and leading to tissue remodelling. Despite the coupling between tumor poroelasticity and interspecific competitive dynamics has recently highlighted how microscopic cells and environment interactions influence growth-associated stresses and tumor pathophysiology, the nonlinear interlacing among biochemical factors and mechanics somehow hindered the possibility of gaining qualitative insights into cells dynamics. Motivated by this, in the present work we recover the linear poroelasticity in order to benefit of a reduced complexity, so first deriving the well-known Lyapunov stability criterion from the thermodynamic dissipation principle and then analysing the stability of the mechanical competition among cells fighting for common space and resources during cancer growth and invasion. At the end, the linear poroelastic model enriched by interspecific dynamics is also exploited to show how growth anisotropy can alter the stress field in spherical tumor masses, by thus indirectly affecting cell mechano-sensing. GraphicAbstract

Morphological and functional analysis of the microcirculation are objective outcome measures that are recommended for use in the presence of clinical signs of altered peripheral blood flow (such as Raynaud phenomenon), which can occur in systemic sclerosis (SSc) and other autoimmune rheumatic diseases. Several advanced non-invasive tools are available for monitoring the microcirculation, including nailfold videocapillaroscopy, which is the best-studied and most commonly used method for distinguishing and quantifying microvascular morphological alterations in SSc. Nailfold videocapillaroscopy can also be used alongside laser Doppler techniques to assist in the early diagnosis and follow-up of patients with dermatomyositis or mixed connective tissue disease. Power Doppler ultrasonography, which has been used for many years to evaluate the vascularity of synovial tissue in rheumatoid arthritis, is another promising tool for the analysis of skin and nailbed capillary perfusion in other autoimmune rheumatic diseases. Other emerging methods include raster-scanning optoacoustic mesoscopy, which offers non-invasive high-resolution 3D visualization of capillaries and has been tested in psoriatic arthritis and SSc. The principle functions and operative characteristics of several non-invasive tools for analysing microvascular changes are outlined in this Review, and the clinical roles of validated or tested imaging methods are discussed for autoimmune rheumatic diseases.

Today, neuronavigation is widely used in daily clinical routine to perform safe and efficient surgery. Augmented reality (AR) interfaces can provide anatomical models and preoperative planning contextually blended with the real surgical scenario, overcoming the limitations of traditional neuronavigators. This study aims to demonstrate the reliability of a new-concept AR headset in navigating complex craniotomies. Moreover, we aim to prove the efficacy of a patient-specific template-based methodology for fast, non-invasive, and fully automatic planning-to-patient registration. The AR platform navigation performance was assessed with an in-vitro study whose goal was twofold: to measure the real-to-virtual 3D target visualization error (TVE), and assess the navigation accuracy through a user study involving 10 subjects in tracing a complex craniotomy. The feasibility of the template-based registration was preliminarily tested on a volunteer. The TVE mean and standard deviation were 1.3 and 0.6 mm. The results of the user study, over 30 traced craniotomies, showed that 97% of the trajectory length was traced within an error margin of 1.5 mm, and 92% within a margin of 1 mm. The in-vivo test confirmed the feasibility and reliability of the patient-specific template for registration. The proposed AR headset allows ergonomic and intuitive fruition of preoperative planning, and it can represent a valid option to support neurosurgical tasks.

This article provides an overview of diffusion kurtosis (DKI) imaging in abdominal oncology. DKI allows for more data on tissue structures than the conventional diffusion model (DWI). However, DKI requires high quality images at b-values greater than 1000 s/mm2 and high signal-to-noise ratio (SNR) that traditionally MRI systems are not able to acquire and therefore there are generally amplified anatomical distortions on the images due to less homogeneity of the field. Advances in both hardware and software on modern MRI scanners have currently enabled ultra-high b-value imaging and offered the ability to apply DKI to multiple extracranial sites. Previous studies have evaluated the ability of DKI to characterize and discriminate tumor grade compared to conventional DWI. Additionally, in several studies the DKI sequences used were based on planar echo (EPI) acquisition, which is susceptible to motion, metal and air artefacts and prone to low SNRs and distortions, leading to low quality images for some small lesions, which may affect the accuracy of the results. Another problem is the optimal b-value of DKI, which remains to be explored and not yet standardized, as well as the manual selection of the ROI, which could affect the accuracy of some parameters.

Growing biological media develop residual stresses to make compatible elastic and inelastic growth-induced deformations, which in turn remodel the tissue properties modifying the actual elastic moduli and transforming an initially isotropic and homogeneous material into a spatially inhomogeneous and anisotropic one. This process is crucial in solid tumor growth mechanobiology, the residual stresses directly influencing tumor aggressiveness, nutrients walkway, necrosis and angiogenesis. With this in mind, we here analyze the problem of a hyperelastic sphere undergoing finite heterogeneous growth, in cases of different boundary conditions and spherical symmetry. By following an analytical approach, we obtain the explicit expression of the tangent elasticity tensor at any point of the material body as a function of the prescribed growth, by involving a small-on-large procedure and exploiting exact solutions for layered media. The results allowed to gain several new insights into how growth-guided mechanical stresses and remodeling processes can influence the solid tumor development. In particular, we highlight that— under hypotheses consistent with mechanical and physiological conditions—auxetic (negative Poisson ratio) transformations of the elastic response of selected growing mass districts could occur and contribute to explain some not yet completely understood phenomena associated to solid tumors. The general approach proposed in the present work could be also helpfully employed to conceive composite materials where ad hoc pre-stress distributions can be designed to obtain auxetic or other selected mechanical properties.

In autoimmune rheumatic diseases, oestrogens can stimulate certain immune responses (including effects on B cells and innate immunity), but can also have dose-related anti-inflammatory effects on T cells, macrophages and other immune cells. By contrast, androgens and progesterone have predominantly immunosuppressive and anti-inflammatory effects. Hormone replacement therapies and oral contraception (and also pregnancy) enhance or decrease the severity of autoimmune rheumatic diseases at a genetic or epigenetic level. Serum androgen concentrations are often low in men and in women with autoimmune rheumatic diseases, suggesting that androgen-like compounds might be a promising therapeutic approach. However, androgen-to-oestrogen conversion (known as intracrinology) is enhanced in inflamed tissues, such as those present in patients with autoimmune rheumatic diseases. In addition, it is becoming evident that the gut microbiota differs between the sexes (known as the microgenderome) and leads to sex-dependent genetic and epigenetic changes in gastrointestinal inflammation, systemic immunity and, potentially, susceptibility to autoimmune or inflammatory rheumatic diseases. Future clinical research needs to focus on the therapeutic use of androgens and progestins or their downstream signalling cascades and on new oestrogenic compounds such as tissue-selective oestrogen complex to modulate altered immune responses.

The aim of this research was to determine any correlations between Dickkopf-1 serum levels (Dkk-1, a natural inhibitor of the Wnt signaling pathway promoting osteoclastogenesis) and the Trabecular Bone Score (TBS), in systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. It also aimed at determining any difference in Dkk-1 serum levels between SSc and RA patients and a control group (CNT) of healthy subjects. A prospective study was carried out in 60 SSc and 60 RA patients and 60 CNT. Dkk-1 serum levels were evaluated by the ELISA method (Quantikine Human Dkk-1 Immunoassay, R&D System, Minneapolis, USA). The severity of microvascular damage was evaluated by nailfold videocapillaroscopy (NVC patterns: “Early,” “Active,” “Late”), in the SSc patients. TBS analysis and bone mineral density (BMD, g/cm2) were measured in all patients/subjects. The SSc patients showed higher Dkk-1 serum levels than RA (p

In numerical ocean modeling, dynamical downscaling is the approach consisting in generating high-resolution regional simulations exploiting the information from coarser resolution models for initial and boundary conditions. Here we evaluate the impacts of downscaling the 1/16 (~ 6–7 km) CMEMS Mediterranean reanalysis model solution into a high-resolution 2-km free-run simulation over the Western Mediterranean basin, focusing on the surface circulation and mesoscale activity. Multi-platform observations from satellite-borne altimeters, high-frequency radar, fixed moorings, and gliders are used for this evaluation, providing insights into the variability from basin to coastal scales. Results show that the downscaling leads to an improvement of the time-averaged surface circulation, especially in the topographically complex area of the Balearic Sea. In particular, the path of the Balearic current is improved in the high-resolution model, also positively affecting transports through the Ibiza Channel. While the high-resolution model produces a similar number of large eddies as CMEMS Med Rea and altimetry, it generates a much larger number of small-scale eddies. Looking into the variability, in the absence of data assimilation, the high-resolution model is not able to properly reproduce the observed phases of mesoscale structures, especially in the southern part of the domain. This negatively affects the representation of the variability of the surface currents interacting with these eddies, highlighting the importance of data assimilation in the high-resolution ocean model in this region to constrain the evolution of these mesoscale structures., This work was supported by La Caixa foundation through the MedClic project (LCF/PR/PR14/11090002) and by the JERICO-NEXT project funded by the European Union Horizon 2020 research and innovation program (grant agreement no. 654410).

Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local setting.

Augmented reality (AR) has been successfully providing surgeons an extensive visual information of surgical anatomy to assist them throughout the procedure. AR allows surgeons to view surgical field through the superimposed 3D virtual model of anatomical details. However, open surgery presents new challenges. This study provides a comprehensive overview of the available literature regarding the use of AR in open surgery, both in clinical and simulated settings. In this way, we aim to analyze the current trends and solutions to help developers and end/users discuss and understand benefits and shortcomings of these systems in open surgery. We performed a PubMed search of the available literature updated to January 2018 using the terms (1) "augmented reality" AND "open surgery", (2) "augmented reality" AND "surgery" NOT "laparoscopic" NOT "laparoscope" NOT "robotic", (3) "mixed reality" AND "open surgery", (4) "mixed reality" AND "surgery" NOT "laparoscopic" NOT "laparoscope" NOT "robotic". The aspects evaluated were the following: real data source, virtual data source, visualization processing modality, tracking modality, registration technique, and AR display type. The initial search yielded 502 studies. After removing the duplicates and by reading abstracts, a total of 13 relevant studies were chosen. In 1 out of 13 studies, in vitro experiments were performed, while the rest of the studies were carried out in a clinical setting including pancreatic, hepatobiliary, and urogenital surgeries. AR system in open surgery appears as a versatile and reliable tool in the operating room. However, some technological limitations need to be addressed before implementing it into the routine practice.