Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers

Aim: Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events. Results: A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC–MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases. Perturbation of metabolites involved in chronic obstructive pulmonary disease, cardiovascular diseases and cancer were identified and discussed. Conclusion: Combining multiplatform metabolic phenotyping with knowledge-based mapping gives mechanistic insights into disease development, which can be applied to next-generation tobacco and nicotine products for comparative risk assessment

On colouring point visibility graphs

In this paper we show that it can be decided in polynomial time whether or not the visibility graph of a given point set is 4-colourable, and such a 4-colouring, if it exists, can also be constructed in polynomial time. We show that the problem of deciding whether the visibility graph of a point set is 5-colourable, is NP-complete. We give an example of a point visibility graph that has chromatic number 6 while its clique number is only 4

A Study of Archiving Strategies in Multi-Objective PSO for Molecular Docking

Molecular docking is a complex optimization problem aimed at predicting the position of a ligand molecule in the active site of a receptor with the lowest binding energy. This problem can be formulated as a bi-objective optimization problem by minimizing the binding energy and the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands. In this context, the SMPSO multi-objective swarm-intelligence algorithm has shown a remarkable performance. SMPSO is characterized by having an external archive used to store the non-dominated solutions and also as the basis of the leader selection strategy. In this paper, we analyze several SMPSO variants based on different archiving strategies in the scope of a benchmark of molecular docking instances. Our study reveals that the SMPSOhv, which uses an hypervolume contribution based archive, shows the overall best performance.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Thermodynamics of Higher Spin Black Holes in AdS3_3

We discuss the thermodynamics of recently constructed three-dimensional higher spin black holes in SL(N,R)\times SL(N,R) Chern-Simons theory with generalized asymptotically-anti-de Sitter boundary conditions. From a holographic perspective, these bulk theories are dual to two-dimensional CFTs with W_N symmetry algebras, and the black hole solutions are dual to thermal states with higher spin chemical potentials and charges turned on. Because the notion of horizon area is not gauge-invariant in the higher spin theory, the traditional approaches to the computation of black hole entropy must be reconsidered. One possibility, explored in the recent literature, involves demanding the existence of a partition function in the CFT, and consistency with the first law of thermodynamics. This approach is not free from ambiguities, however, and in particular different definitions of energy result in different expressions for the entropy. In the present work we show that there are natural definitions of the thermodynamically conjugate variables that follow from careful examination of the variational principle, and moreover agree with those obtained via canonical methods. Building on this intuition, we derive general expressions for the higher spin black hole entropy and free energy which are written entirely in terms of the Chern-Simons connections, and are valid for both static and rotating solutions. We compare our results to other proposals in the literature, and provide a new and efficient way to determine the generalization of the Cardy formula to a situation with higher spin charges.Comment: 30 pages, PDFLaTeX; v2: typos corrected, explicit expressions for the free energy adde

Limbal stem cell transplantation: current perspectives

Marwan Raymond Atallah, Sotiria Palioura, Victor L Perez, Guillermo Amescua Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD). In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers the best results. Future studies aim at improving cellular expansion and finding different sources of stem cells. Keywords: limbal stem cell deficiency (LSCD), simple limbal epithelial transplantation (SLET), cultivated limbal epithelial transplantation (CLET), keratolimbal allograft (KLAL

Owning an overweight or underweight body: distinguishing the physical, experienced and virtual body

Our bodies are the most intimately familiar objects we encounter in our perceptual environment. Virtual reality provides a unique method to allow us to experience having a very different body from our own, thereby providing a valuable method to explore the plasticity of body representation. In this paper, we show that women can experience ownership over a whole virtual body that is considerably smaller or larger than their physical body. In order to gain a better understanding of the mechanisms underlying body ownership, we use an embodiment questionnaire, and introduce two new behavioral response measures: an affordance estimation task (indirect measure of body size) and a body size estimation task (direct measure of body size). Interestingly, after viewing the virtual body from first person perspective, both the affordance and the body size estimation tasks indicate a change in the perception of the size of the participant’s experienced body. The change is biased by the size of the virtual body (overweight or underweight). Another novel aspect of our study is that we distinguish between the physical, experienced and virtual bodies, by asking participants to provide affordance and body size estimations for each of the three bodies separately. This methodological point is important for virtual reality experiments investigating body ownership of a virtual body, because it offers a better understanding of which cues (e.g. visual, proprioceptive, memory, or a combination thereof) influence body perception, and whether the impact of these cues can vary between different setups

Standardised description of health and social care: A systematic review of use of the ESMS/DESDE (European Service Mapping Schedule/Description and Evaluation of Services and DirectoriEs)

Background: Evidence-informed planning and interpretation of research results both require standardised description of local care delivery context. Such context analysis descriptions should be comparable across regions and countries to allow benchmarking and organizational learning, and for research findings to be interpreted in context. The European Service Mapping Schedule (ESMS) is a classification of adult mental health services that was later adapted for the assessment of health and social systems research (Description and Evaluation of Services and DirectoriEs - DESDE). The aim of the study was to review the diffusion and use of the ESMS/DESDE system in health and social care and its impact in health policy and decision-making. Method: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (1997–2018). Results: Out of 155 papers mentioning ESMS/DESDE, 71 have used it for service research and planning. The classification has been translated into eight languages and has been used by seven international research networks. Since 2000, it has originated 11 instruments for health system research with extensive analysis of their metric properties. The ESMS/DESDE coding system has been used in 585 catchment areas in 34 countries for description of services delivery at local, regional and national levels. Conclusions: The ESMS/DESDE system provides a common terminology, a classification of care services, and a set of tools allowing a variety of aims to be addressed in healthcare and health systems research. It facilitates comparisons across and within countries for evidence-informed planning

Patient safety in dentistry: development of a candidate 'never event' list for primary care

Introduction The 'never event' concept is often used in secondary care and refers to an agreed list of patient safety incidents that 'should not happen if the necessary preventative measures are in place'. Such an intervention may raise awareness of patient safety issues and inform team learning and system improvements in primary care dentistry. Objective To identify and develop a candidate never event list for primary care dentistry. Methods A literature review, eight workshops with dental practitioners and a modified Delphi with 'expert' groups were used to identify and agree candidate never events. Results Two-hundred and fifty dental practitioners suggested 507 never events, reduced to 27 distinct possibilities grouped across seven themes. Most frequently occurring themes were: 'checking medical history and prescribing' (119, 23.5%) and 'infection control and decontamination' (71, 14%). 'Experts' endorsed nine candidate never event statements with one graded as 'extreme risk' (failure to check past medical history) and four as 'high risk' (for example, extracting wrong tooth). Conclusion Consensus on a preliminary list of never events was developed. This is the first known attempt to develop this approach and an important step in determining its value to patient safety. Further work is necessary to develop the utility of this method

Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain

Earlier reports showed that hyperplasia of sympathoadrenal cell precursors during embryogenesis in Nf1-deficient mice is independent of Nf1’s role in down-modulating RAS-MAPK signaling. We demonstrate in zebrafish that nf1 loss leads to aberrant activation of RAS signaling in MYCN-induced neuroblastomas that arise in these precursors, and that the GTPase-activating protein (GAP)-related domain (GRD) is sufficient to suppress the acceleration of neuroblastoma in nf1-deficient fish, but not the hypertrophy of sympathoadrenal cells in nf1 mutant embryos. Thus, even though neuroblastoma is a classical “developmental tumor”, NF1 relies on a very different mechanism to suppress malignant transformation than it does to modulate normal neural crest cell growth. We also show marked synergy in tumor cell killing between MEK inhibitors (trametinib) and retinoids (isotretinoin) in primary nf1a-/- zebrafish neuroblastomas. Thus, our model system has considerable translational potential for investigating new strategies to improve the treatment of very high-risk neuroblastomas with aberrant RAS-MAPK activation