How do patients' clinical phenotype and the physiological mechanisms of the operations impact the choice of bariatric procedure?

Bariatric surgery is currently the most effective option for the treatment of morbid obesity and its associated comorbidities. Recent clinical and experimental findings have challenged the role of mechanical restriction and caloric malabsorption as the main mechanisms for weight loss and health benefits. Instead, other mechanisms including increased levels of satiety gut hormones, altered gut microbiota, changes in bile acid metabolism, and/or energy expenditure have been proposed as explanations for benefits of bariatric surgery. Beside the standard proximal Roux-en-Y gastric bypass and the biliopancreatic diversion with or without duodenal switch, where parts of the small intestine are excluded from contact with nutrients, resectional techniques like the sleeve gastrectomy (SG) have recently been added to the armory of bariatric surgeons. The variation of weight loss and glycemic control is vast between but also within different bariatric operations. We surveyed members of the Swiss Society for the Study of Morbid Obesity and Metabolic Disorders to assess the extent to which the phenotype of patients influences the choice of bariatric procedure. Swiss bariatric surgeons preferred Roux-en-Y gastric bypass and SG for patients with type 2 diabetes mellitus and patients with a body mass index >50 kg/m(2), which is consistent with the literature. An SG was preferred in patients with a high anesthetic risk or previous laparotomy. The surgeons' own experience was a major determinant as there is little evidence in the literature for this approach. Although trends will come and go, evidence-based medicine requires a rigorous examination of the proof to inform clinical practice

Towards Efficient Full Pose Omnidirectionality with Overactuated MAVs

Omnidirectional MAVs are a growing field, with demonstrated advantages for aerial interaction and uninhibited observation. While systems with complete pose omnidirectionality and high hover efficiency have been developed independently, a robust system that combines the two has not been demonstrated to date. This paper presents VoliroX: a novel omnidirectional vehicle that can exert a wrench in any orientation while maintaining efficient flight configurations. The system design is presented, and a 6 DOF geometric control that is robust to singularities. Flight experiments further demonstrate and verify its capabilities.Comment: 10 pages, 6 figures, ISER 2018 conference submissio

Exploiting the Symmetry of the Resonator Mode to Enhance PELDOR Sensitivity.

Pulsed electron paramagnetic resonance (EPR) spectroscopy using microwaves at two frequencies can be employed to measure distances between pairs of paramagnets separated by up to 10 nm. The method, combined with site-directed mutagenesis, has become increasingly popular in structural biology for both its selectivity and capability of providing information not accessible through more standard methods such as nuclear magnetic resonance and X-ray crystallography. Despite these advantages, EPR distance measurements suffer from poor sensitivity. One contributing factor is technical: since 65 MHz typically separates the pump and detection frequencies, they cannot both be located at the center of the pseudo-Lorentzian microwave resonance of a single-mode resonator. To maximize the inversion efficiency, the pump pulse is usually placed at the center of the resonance, while the observer frequency is placed in the wing, with consequent reduction in sensitivity. Here, we consider an alternative configuration: by spacing pump and observer frequencies symmetrically with respect to the microwave resonance and by increasing the quality factor, valuable improvement in the signal-to-noise ratio can be obtained

Identification and pharmacological inactivation of the MYCN gene network as a therapeutic strategy for neuroblastic tumor cells

This research was originally published in Journal of Biological Chemistry. Olesya Chayka, Cosimo Walter D’Acunto, Odette Middleton, Maryam Arab, and Arturo Sala. Identification and Pharmacological Inactivation of the MYCN Gene Network as a Therapeutic Strategy for Neuroblastic Tumor Cells. Journal of Biological Chemistry. 2015; Vol 290 (4) :pp. 2198 - 2212. © the American Society for Biochemistry and Molecular Biology.This article has been made available through the Brunel Open Access Publishing Fund.The MYC family of transcription factors consists of three well characterized members, c-MYC, L-MYC, and MYCN, deregulated in the majority of human cancers. In neuronal tumors such as neuroblastoma, MYCN is frequently activated by gene amplification, and reducing its expression by RNA interference has been shown to promote growth arrest and apoptosis of tumor cells. From a clinical perspective, RNA interference is not yet a viable option, and small molecule inhibitors of transcription factors are difficult to develop. We therefore planned to identify, at the global level, the genes interacting functionally with MYCN required to promote fitness of tumor cells facing oncogenic stress. To find genes whose inactivation is synthetically lethal to MYCN, we implemented a genome-wide approach in which we carried out a drop-out shRNA screen using a whole genome library that was delivered into isogenic neuroblastoma cell lines expressing or not expressing MYCN. After the screen, we selected for in-depth analysis four shRNAs targeting AHCY, BLM, PKMYT1, and CKS1B. These genes were chosen because they are directly regulated by MYC proteins, associated with poor prognosis of neuroblastoma patients, and inhibited by small molecule compounds. Mechanistically, we found that BLM and PKMYT1 are required to limit oncogenic stress and promote stabilization of the MYCN protein. Cocktails of small molecule inhibitors of CKS1B, AHCY, BLM, and PKMYT1 profoundly affected the growth of all neuroblastoma cell lines but selectively caused death of MYCN-amplified cells. Our findings suggest that drugging the MYCN network is a promising avenue for the treatment of high risk, neuroblastic cancers.SPARKS and the Neuroblastoma Society

Time and dose dependency of bone-sarcomas in patients injected with radium-224

The time course and dose dependency of the incidence of bone-sarcomas among 900 German patients treated with high doses of radium-224 is analysed in terms of a proportional hazards model with a log-normal dependency of time to tumor and a linear-quadratic dose relation. The deduced dose dependency agrees well with a previous analysis in terms of a non-parametric proportional hazards model, and confirms the temporal distribution which has been used in the Radioepidemiological Tables of NIH. However, the linear-quadratic dose-response model gives a risk estimate for low doses which is somewhat less than half that obtained under the assumption of linearity. Dedicated to Prof. W. Jacobi on the occasion of his 60th birthday Work performed under Euratom contracts BI6-D-083-D, BI6-F-111-D, U.S. Department of Energy contract DE-AC 02-76 EV-00119, the U.S. National Cancer Institut

Formal Definitions of Unbounded Evolution and Innovation Reveal Universal Mechanisms for Open-Ended Evolution in Dynamical Systems

Open-ended evolution (OEE) is relevant to a variety of biological, artificial and technological systems, but has been challenging to reproduce in silico. Most theoretical efforts focus on key aspects of open-ended evolution as it appears in biology. We recast the problem as a more general one in dynamical systems theory, providing simple criteria for open-ended evolution based on two hallmark features: unbounded evolution and innovation. We define unbounded evolution as patterns that are non-repeating within the expected Poincare recurrence time of an equivalent isolated system, and innovation as trajectories not observed in isolated systems. As a case study, we implement novel variants of cellular automata (CA) in which the update rules are allowed to vary with time in three alternative ways. Each is capable of generating conditions for open-ended evolution, but vary in their ability to do so. We find that state-dependent dynamics, widely regarded as a hallmark of life, statistically out-performs other candidate mechanisms, and is the only mechanism to produce open-ended evolution in a scalable manner, essential to the notion of ongoing evolution. This analysis suggests a new framework for unifying mechanisms for generating OEE with features distinctive to life and its artifacts, with broad applicability to biological and artificial systems.Comment: Main document: 17 pages, Supplement: 21 pages Presented at OEE2: The Second Workshop on Open-Ended Evolution, 15th International Conference on the Synthesis and Simulation of Living Systems (ALIFE XV), Canc\'un, Mexico, 4-8 July 2016 (http://www.tim-taylor.com/oee2/

Gauge invariant definition of the jet quenching parameter

In the framework of Soft-Collinear Effective Theory, the jet quenching parameter, $\hat{q}$, has been evaluated by adding the effect of Glauber gluon interactions to the propagation of a highly-energetic collinear parton in a medium. The result, which holds in covariant gauges, has been expressed in terms of the expectation value of two Wilson lines stretching along the direction of the four-momentum of the parton. In this paper, we show how that expression can be generalized to an arbitrary gauge by the addition of transverse Wilson lines. The transverse Wilson lines are explicitly computed by resumming interactions of the parton with Glauber gluons that appear only in non-covariant gauges. As an application of our result, we discuss the contribution to $\hat{q}$ coming from transverse momenta of order $g^2T$ in a medium that is a weakly-coupled quark-gluon plasma.Comment: 31 pages, 7 figures; journal versio