Multibody dynamics analysis (MDA) as a numerical modelling tool to reconstruct the function and palaeobiology of extinct organisms

Recent advances in computer technology have substantially changed the field of palaeontology in the last two decades. Palaeontologists now have a whole new arsenal of powerful digital techniques available to study fossil organisms in unprecedented detail and to test hypotheses regarding function and behaviour. Multibody dynamics analysis (MDA) is one of these techniques and although it originated as a tool used in the engineering and automotive industry, it holds great potential to address palaeontological questions as well. MDA allows the simulation of dynamic movements in complex objects consisting of multiple linked components. As such, this technique is ideally suited to model biological structures and to obtain quantifiable results that can be used to test the function of musculoskeletal systems rigorously. However, despite these advantages, MDA has seen a slow uptake by the palaeontological community. The most likely reason for this lies in the steep learning curve and complexity of the method. This paper provides an overview of the underlying principles of MDA and outlines the main steps involved in conducting analyses. A number of recent studies using MDA to reconstruct the palaeobiology of fossil organisms are presented and the potential for future studies is discussed. Similar to other computational techniques, including finite element analysis and computational fluid dynamics, the non‐invasive and exploratory power of MDA makes it ideally suited to study the form and function in vertebrates for which no modern analogues exist

210Po Log-normal distribution in human urines: Survey from Central Italy people

The death in London of the former secret service agent Alexander Livtinenko on 23 November 2006 generally attracted the attention of the public to the rather unknown radionuclide 210Po. This paper presents the results of a monitoring programme of 210Po background levels in the urines of noncontaminated people living in Central Italy (near the Republic of S. Marino). The relationship between age, sex, years of smoking, number of cigarettes per day, and 210Po concentration was also studied. The results indicated that the urinary 210Po concentration follows a surprisingly perfect Log-normal distribution. Log 210Po concentrations were positively correlated to age (p < 0.0001), number of daily smoked cigarettes (p = 0.006), and years of smoking (p = 0.021), and associated to sex (p = 0.019). Consequently, this study provides upper reference limits for each sub-group identified by significantly predictive variables

Hemosuccus Pancreaticus in the Era of Capsule Endoscopy and Double Balloon Enteroscopy Complicated by Multifocal Mycobacterium chelonae/abscessus Infection

Hemosuccus pancreaticus is a rare etiology of obscure gastrointestinal bleeding characterized by bleeding into the pancreatic duct. The diagnosis may be delayed for months to years, due to the episodic nature of bleeding and failure to consider the diagnosis. Patients often undergo multiple endoscopies and radiologic evaluations prior to diagnosis. Incidental gastrointestinal findings may lead to unnecessary endoscopic and surgical interventions. This report describes a patient with hemosuccus pancreaticus diagnosed in the era of video capsule endoscopy and double balloon enteroscopy, whose management was complicated by multifocal Mycobacteria chelonae/abscessus infection

A comparison of Finite Elements for Nonlinear Beams: The absolute nodal coordinate and geometrically exact formulations

Two of the most popular finite element formulations for solving nonlinear beams are the absolute nodal coordinate and the geometrically exact approaches. Both can be applied to problems with very large deformations and strains, but they differ substantially at the continuous and the discrete levels. In addition, implementation and run-time computational costs also vary significantly. In the current work, we summarize the main features of the two formulations, highlighting their differences and similarities, and perform numerical benchmarks to assess their accuracy and robustness. The article concludes with recommendations for the choice of one formulation over the other

Anti-Neuroinflammatory effects of the extract of Achillea fragrantissima

<p>Abstract</p> <p>Background</p> <p>The neuroinflammatory process plays a central role in the initiation and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, and involves the activation of brain microglial cells. During the neuroinflammatory process, microglial cells release proinflammatory mediators such as cytokines, matrix metalloproteinases (MMP), Reactive oxygen species (ROS) and nitric oxide (NO). In the present study, extracts from 66 different desert plants were tested for their effect on lipopolysaccharide (LPS) - induced production of NO by primary microglial cells. The extract of <it>Achillea fragrantissima </it>(<it>Af</it>)<it/>, which is a desert plant that has been used for many years in traditional medicine for the treatment of various diseases, was the most efficient extract, and was further studied for additional anti-neuroinflammatory effects in these cells.</p> <p>Methods</p> <p>In the present study, the ethanolic extract prepared from <it>Af </it>was tested for its anti-inflammatory effects on lipopolysaccharide (LPS)-activated primary cultures of brain microglial cells. The levels of the proinflammatory cytokines interleukin1β (IL-1β) and tumor necrosis factor-α (TNFα) secreted by the cells were determined by reverse transcriptase-PCR and Enzyme-linked immunosorbent assay (ELISA), respectively. NO levels secreted by the activate cells were measured using Griess reagent, ROS levels were measured by 2'7'-dichlorofluorescein diacetate (DCF-DA), MMP-9 activity was measured using gel zymography, and the protein levels of the proinflammatory enzymes cyclooxygenase-2 (COX-2) and induced nitric oxide synthase (iNOS) were measured by Western blot analysis. Cell viability was assessed using Lactate dehydrogenase (LDH) activity in the media conditioned by the cells or by the crystal violet cell staining.</p> <p>Results</p> <p>We have found that out of the 66 desert plants tested, the extract of <it>Af </it>was the most efficient extract and inhibited ~70% of the NO produced by the LPS-activated microglial cells, without affecting cell viability. In addition, this extract inhibited the LPS - elicited expression of the proinflammatory mediators IL-1β, TNFα, MMP-9, COX-2 and iNOS in these cells.</p> <p>Conclusions</p> <p>Thus, phytochemicals present in the <it>Af </it>extract could be beneficial in preventing/treating neurodegenerative diseases in which neuroinflammation is part of the pathophysiology.</p

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks