Multiphysics and Thermodynamic Formulations for Equilibrium and Non-equilibrium Interactions: Non-linear Finite Elements Applied to Multi-coupled Active Materials

[EN] Combining several theories this paper presents a general multiphysics framework applied to the study of coupled and active materials, considering mechanical, electric, magnetic and thermal fields. The framework is based on thermodynamic equilibrium and non-equilibrium interactions, both linked by a two-temperature model. The multi-coupled governing equations are obtained from energy, momentum and entropy balances; the total energy is the sum of thermal, mechanical and electromagnetic parts. The momentum balance considers mechanical plus electromagnetic balances; for the latter the Abraham rep- resentation using the Maxwell stress tensor is formulated. This tensor is manipulated to automatically fulfill the angular momentum balance. The entropy balance is for- mulated using the classical Gibbs equation for equilibrium interactions and non-equilibrium thermodynamics. For the non-linear finite element formulations, this equation requires the transformation of thermoelectric coupling and conductivities into tensorial form. The two-way thermoe- lastic Biot term introduces damping: thermomechanical, pyromagnetic and pyroelectric converse electromagnetic dynamic interactions. Ponderomotrix and electromagnetic forces are also considered. The governing equations are converted into a variational formulation with the resulting four-field, multi-coupled formalism implemented and val- idated with two custom-made finite elements in the research code FEAP. Standard first-order isoparametric eight-node elements with seven degrees of freedom (dof) per node (three displacements, voltage and magnetic scalar potentials plus two temperatures) are used. Non-linearities and dynamics are solved with Newton-Raphson and New- mark-b algorithms, respectively. Results of thermoelectric, thermoelastic, thermomagnetic, piezoelectric, piezomag- netic, pyroelectric, pyromagnetic and galvanomagnetic interactions are presented, including non-linear depen- dency on temperature and some second-order interactions.This research was partially supported by grants CSD2008-00037 Canfranc Underground Physics, Polytechnic University of Valencia under programs PAID 02-11-1828 and 05-10-2674. The first author used the grant Generalitat Valenciana BEST/2014/232 for the completion of this work.Pérez-Aparicio, JL.; Palma, R.; Taylor, R. (2016). Multiphysics and Thermodynamic Formulations for Equilibrium and Non-equilibrium Interactions: Non-linear Finite Elements Applied to Multi-coupled Active Materials. Archives of Computational Methods in Engineering. 23:535-583. https://doi.org/10.1007/s11831-015-9149-9S53558323Abraham M (1910) Sull’elettrodinamica di Minkowski. Rend Circ Mat 30:33–46Allik H, Hughes TJR (1970) Finite elment method for piezoelectric vibration. Int J Numer Methods Eng 2:151–157Antonova EE, Looman DC (2005) Finite elements for thermoelectric device analysis in ANSYS. In: International conference on thermoelectricsAtulasimha J, Flatau AB (2011) A review of magnetostrictive iron–gallium alloys. Smart Mater Struct 20:1–15Ballato A (1995) Piezoelectricity: old effect, new thrusts. IEEE Trans Ultrason Ferroelectr Freq Control 42(5):916–926Baoyuan S, Jiantong W, Jun Z, Min Q (2003) A new model describing physical effects in crystals: the diagrammatic and analytic methods for macro-phenomenological theory. J Mater Process Technol 139:444–447Bargmann S, Steinmann P (2005) Finite element approaches to non-classical heat conduction in solids. Comput Model Eng Sci 9(2):133–150Bargmann S, Steinmann P (2006) Theoretical and computational aspects of non-classical thermoelasticity. Comput Methods Appl Mech Eng 196:516–527Bargmann S, Steinmann P (2008) Modeling and simulation of first and second sound in solids. Int J Solids Struct 45:6067–6073Barnett SM (2010) Resolution of the Abraham–Minkowski dilemma. Phys Rev Lett 104:070401Benbouzid MH, Meunier G, Meunier G (1995) Dynamic modelling of giant magnetostriction in Terfenol-D rods by the finite element method. IEEE Trans Magn 31(3):1821–1824Benbouzid MH, Reyne G, Meunier G (1993) Nonlinear finite element modelling of giant magnetostriction. IEEE Trans Magn 29(6):2467–2469Benbouzid MH, Reyne G, Meunier G (1995) Finite elment modelling of magnetostrictive devices: investigations for the design of the magnetic circuit. IEEE Trans Magn 31(3):1813–1816Besbes M, Ren Z, Razek A (1996) Finite element analysis of magneto-mechanical coupled phenomena in magnetostrictive materials. IEEE Trans Magn 32(3):1058–1061Biot MA (1956) Thermoelasticity and irreversible thermodynamics. J Appl Phys 27(3):240–253Bisio G, Cartesegna M, Rubatto G (2001) Thermodynamic analysis of elastic systems. Energy Convers Manag 42:799–812Blun SL (1974) Materials for radiation detection. National Academy of Sciences, WashingtonBonet J, Wood RD (1997) Nonlinear continuum mechanics for finite element analysis. Cambridge University Press, CambridgeBorovik-Romanov AS (1960) Piezomagnetism in the antiferromagnetic fluorides of cobalt and manganese. Sov Phys 11:786Bowyer P (2005) The momentum of light in media: the Abraham–Minkowski controversy. http://bit.ly/1M7wyATBrauer JR, Ruehl JJ, MacNeal BE, Hirtenfelder F (1995) Finite element analysis of Hall effect and magnetoresistance. IEEE Trans Electron Devices 42(2):328–333Bustamante R, Dorfmann A, Ogden RW (2009) On electric body forces and Maxwell stresses in nonlinearly electroelastic solids. Int J Eng Sci 47:1131–1141Callen HB (1948) The application of Onsager’s reciprocal relations to thermoelectric, thermomagnetic, and galvanomagnetic effects. Phys Rev 73(11):1349–1358Callen HB (1985) Thermodynamics and an introduction to thermostatistics. Wiley, New YorkCarter JP, Booker JR (1989) Finite element analysis of coupled thermoelasticity. Comput Struct 31(1):73–80Cattaneo C (1938) Sulla conduzione del calore. Atti Semin Mat Fis Univ Modena 3:83–1013Chaplik AV (2000) Some exact solutions for the classical Hall effect in an inhomogeneous magnetic field. JETP Lett 72:503Chen PJ, Gurtin ME (1968) On a theory of heat conduction involving two temperatures. J Z Angew Math Phys ZAMP 19(4):614–627Chu LJ, Haus HA, Penfield P (1966) The force density in polarizable and magnetizable fluids. In: Proceedings of the IEEEClin Th, Turenne S, Vasilevskiy D, Masut RA (2009) Numerical simulation of the thermomechanical behavior of extruded bismuth telluride alloy module. J Electron Mater 38(7):994–1001Coleman BD (1964) Thermodynamics of materials with memory. Arch Ration Mech Anal 17:1–46de Groot SR (1961) Non-equilibrium themodynamics of systems in an electromagnetic field. J Nucl Energy C Plasma Phys 2:188–194de Groot SR, Mazur P (1984) Non-equilibrium thermodynamics. Dover, MineolaDebye P (1913) On the theory of anomalous dispersion in the region of long-wave electromagnetic radiation. Verh dtsch phys Ges 15:777–793del Castillo LF, García-Colín LS (1986) Thermodynamic basis for dielectric relaxation in complex materials. Phys Rev B 33(7):4944–4951Delves RT (1964) Figure of merit for Ettingshausen cooling. Br J Appl Phys 15:105–106Dorf RC (1997) The electrical engineering handbook. CRC Press, UKEarle R, Richards JFC (1956) Theophrastus: on stones. Ohio State University, ColumbusEbling D, Jaegle M, Bartel M, Jacquot A, Bottner H (2009) Multiphysics simulation of thermoelectric systems for comparison with experimental device performance. J Electron Mater 38(7):1456–1461El-Karamany AS, Ezzat MA (2011) On the two-temperature Green–Naghdi thermoelasticity theories. J Therm Stress 34:1207–1226Eringen AC (1980) Mechanics of continua. Robert E Krieger, MalabarEringen AC, Maugin GA (1990) Electrodynamics of continua I. Springer, New YorkErsoy Y (1984) A new nonlinear constitutive theory for conducting magnetothermoelastic solids. Int J Eng Sci 22(6):683–705Ersoy Y (1986) A new nonlinear constitutive theory of electric and heat conductions for magnetoelastothermo-electrical anisotropic solids. Int J Eng Sci 24(6):867–882Ferrari A, Mittica A (2013) Thermodynamic formulation of the constitutive equations for solids and fluids. Energy Convers Manag 66:77–86Galushko D, Ermakov N, Karpovski M, Palevski A, Ishay JS, Bergman DJ (2005) Electrical, thermoelectric and thermophysical properties of hornet cuticle. Semicond Sci Technol 20:286–289Gao JL, Du QG, Zhang XD, Jiang XQ (2011) Thermal stress analysis and structure parameter selection for a Bi2Te3-based thermoelectric module. J Electron Mater 40(5):884–888Gaudenzi P, Bathe KJ (1995) An iterative finite element procedure for the analysis of piezoelectric continua. J Intell Mater Syst Struct 6:266–273Gavela D, Pérez-Aparicio JL (1998) Peltier pellet analysis with a coupled, non-linear 3D finite element model. In: 4th European workshop on thermoelectricsGoudreau GL, Taylor RL (1972) Evaluation of numerical integration methods in elastodynamics. Comput Methods Appl Mech Eng 2:69–97Griffiths DJ (1999) Introduction to electrodynamics. Prentice-Hall Inc, Upper Saddle RiverGros L, Reyne G, Body C, Meunier G (1998) Strong coupling magneto mechanical methods applied to model heavy magnetostrictive actuators. IEEE Trans Magn 34(5):3150–3153Gurtin ME, Williams WO (1966) On the Clausius–Duhem inequality. J Z Angew Math Phys ZAMP 17(5):626–633Hamader VM, Patil TA, Chovan SH (1987) Free vibration response of two-dimensional magneto-electro-elastic laminated plates. Build Mater Sci 9:249–253Hausler C, Milde G, Balke H, Bahr HA, Gerlach G (2001) 3-D modeling of pyroelectric sensor arrays part I: multiphysics finite-element simulation. IEEE Sens J 8(12):2080–2087He Y (2004) Heat capacity, thermal conductivity and thermal expansion of barium titanate-based ceramics. Thermochimica 419:135–141Hernández-Lemus E, Orgaz E (2002) Hysteresis in nonequilibrium steady states: the role of dissipative couplings. Rev Mex Fís 48:38–45Hinds EA (2009) Momentum exchange between light and a single atom: Abraham or Minkowski? Phys Rev Lett 102:050403Hirsinger L, Billardon R (1995) Magneto-elastic finite element analysis including magnetic forces and magnetostriction effects. IEEE Trans Magn 31(3):1877–1880Huang MJ, Chou PK, Lin MC (2008) An investigation of the thermal stresses induced in a thin-film thermoelectric cooler. J Therm Stress 31:438–454IEEE Standards Board (1988) IEEE standard on piezoelectricity. ANSI/IEEE Std 176-1987. doi: 10.1109/IEEESTD.1988.79638IEEE Standards Board (1991) IEEE standard on magnetostrictive materials: piezomagnetic nomenclature. IEEE Std 319-1990. doi: 10.1109/IEEESTD.1991.101048Ioffe Institute (2013) INSb—indium antimonide. Ioffe Institute. www.ioffe.rssi.ru/SVA/NSM/Semicond/InSb/index.htmlJackson JD (1962) Classical electrodynamics. Wiley, New YorkJaegle M (2008) Multiphysics simulation of thermoelectric systems—modeling of Peltier—cooling and thermoelectric generation. In: Proceedings of the COMSOLJaegle M, Bartel M, Ebling D, Jacquot A, Bottner H (2008) Multiphysics simulation of thermoelectric systems. In: European conference on thermoelectrics ECT2008Jiménez JL, Campos I (1996) Advanced electromagnetism: foundations, theory and applications, chapter The balance equations of energy and momentum in classical electrodynamics. World Scientific Publishing, SingaporeJohnstone S (2008) Is there potential for use of the Hall effect in analytical science? Analyst 133:293–296Jou D, Lebon G (1996) Extended irreversible thermodynamics. Springer, BerlinKaltenbacher M, Kaltenbacher B, Hegewald T, Lerch R (2010) Finite element formulation for ferroelectric hysteresis of piezoelectric materials. J Intell Mater Syst Struct 21:773–785Kaltenbacher M, Meiler M, Ertl M (2009) Physical modeling and numerical computation of magnetostriction. Int J Comput Math Electr Electron Eng 28(4):819–832Kamlah M, Bohle U (2001) Finite element analysis of piezoceramic components taking into account ferroelectric hysteresis behavior. Int J Solids Struct 38:605–633Kannan KS, Dasgupta A (1997) A nonlinear Galerkin finite-element theory for modeling magnetostrictive smart structures. Smart Mater Struct 6:341–350Kiang J, Tong L (2010) Nonlinear magneto-mechanical finite element analysis of Ni–Mn–Ga single crystals. Smart Mater Struct 19:1–17Kinsler P, Favaro A, McCall MW (2009) Four Poynting theorems. Eur J Phys 30:983–993Klinckel S, Linnemann K (2008) A phenomenological constitutive model for magnetostrictive materials and ferroelectric ceramics. Proc Appl Math Mech 8:10507–10508Kosmeier D (2013) Hornets: Gentle Giants! Wikipedia: the free encyclopedia. www.hornissenschutz.de/hornets.htmLahmer T (2008) Forward and inverse problems in piezoelectricity. PhD thesis, Universität Erlangen-NürnbergLandau LD, Lifshitz EM (1982) Mechanics. Butterworth-Heinemann, OxfordLandau LD, Lifshitz EM (1984) Electrodynamics of continuous media. Pergamon Press, OxfordLandis CM (2002) A new finite-element formulation for electromechanical boundary value problems. Int J Numer Methods Eng 55:613–628Díaz Lantada A (2011) Handbook of active materials for medical devices: advances and applications. CRC Press, Boca RatonLebon G, Jou D, Casas-Vázquez J (2008) Understanding non-equilibrium thermodynamics. Springer, BerlinLinnemann K, Klinkel S (2006) A constitutive model for magnetostrictive materials—theory and finite element implementation. Proc Appl Math Mech 6:393–394Linnemann K, Klinkel S, Wagner W (2009) A constitutive model for magnetostrictive and piezoelectric materials. Int J Solids Struct 46:1149–1166Llebot JE, Jou D, Casas-Vázquez J (1983) A thermodynamic approach to heat and electric conduction in solids. Physica 121(A):552–562Lu X, Hanagud V (2004) Extended irreversible thermodynamics modeling for self-heating and dissipation in piezoelectric ceramics. IEEE Trans Ultrason Ferroelectr Freq Control 51(12):1582–1592Lubarda VA (2004) On thermodynamic potentials in linear thermoelasticity. Int J Solids Struct 41:7377–7398Mansuripur M (2012) Trouble with the lorentz law of force: incompatibility with special relativity and momentum conservation. Phys Rev Lett 108:193901Maruszewski B, Lebon G (1986) An extended irreversible thermodynamic description of electrothermoelastic semiconductors. Int J Eng Sci 24(4):583–593McMeeking RM, Landis CM (2005) Electrostatic forces and stored energy for deformable dielectric materials. J Appl Mech 72:581–590McMeeking RM, Landis CM, Jimenez MA (2007) A principle of virtual work for combined electrostatic and mechanical loading of materials. Int J Non Linear Mech 42:831–838MELCOR (2000) Thermoelectric handbook. Melcor, a unit of Laird Technologies. http://www.lairdtech.comMinkowski H (1908) Nachr. ges. wiss. Gottingen 53Naranjo B, Gimzewski JK, Putterman S (2005) Observation of nuclear fusion driven by a pyroelectric crystal. Nature 28(434):1115–1117Nédélec JC (1980) Mixed finite elements in $${R}^3$$ R 3 . Numer Math 35:314–345Nettleton RE, Sobolev SL (1995) Applications of extended thermodynamics to chemical, rheological, and transport processes: a special survey part I. approaches and scalar rate processes. J Non-Equilib Thermodyn 20:205–229Nettleton RE, Sobolev SL (1995) Applications of extended thermodynamics to chemical, rheological, and transport processes: a special survey part II. vector transport processes, shear relaxation and rheology. J Non-Equilib Thermodyn 20:297–331Nettleton RE, Sobolev SL (1996) Applications of extended thermodynamics to chemical, rheological, and transport processes: a special survey part III. wave phenomena. J Non-Equilib Thermodyn 21:1–16Newmark N (1959) A method of computation for structural dynamics. ASCE J Eng Mech 85:67–94Newnham RE (2005) Properties of materials: anisotropy, symmetry, structure. Oxford University Press, OxfordNour AE, Abd-Alla N, Maugin GA (1990) Nonlinear equations for thermoelastic magnetizable conductors. Int J Eng Sci 27(7):589–603Nowacki A (1962) International series of monographs in aeronautics and astronautics. Pergamon Press, OxfordOkumura H, Hasegawa Y, Nakamura H, Yamaguchi S (1999) A computational model of thermoelectric and thermomagnetic semiconductors. In: 18th international conference on thermoelectricsOkumura H, Yamaguchi S, Nakamura H, Ikeda K, Sawada K (1998) Numerical computation of thermoelectric and thermomagnetic effects. In: 17th international conference on thermoelectricsOliver X, Agelet C (2000) Continuum mechanics for engineers. Edicions UPC, Barcelona. http://hdl.handle.net/2099.3/36197Shankar K, Kondaiah P, Ganesan N (2013) Pyroelectric and pyromagnetic effects on multiphase magneto-electro-elastic cylindrical shells for axisymmetric temperature. Smart Mater Struct 22(2):025007Palma R, Pérez-Aparicio JL, Bravo R (2013) Study of hysteretic thermoelectric behavior in photovoltaic materials using the finite element method, extended thermodynamics and inverse problems. Energy Convers Manag 65:557–563Palma R, Pérez-Aparicio JL, Taylor RL (2012) Non-linear finite element formulation applied to thermoelectric materials under hyperbolic heat conduction model. Comput Method Appl Mech Eng 213–216:93–103Palma R, Rus G, Gallego R (2009) Probabilistic inverse problem and system uncertainties for damage detection in piezoelectrics. Mech Mater 41:1000–1016Pérez-Aparicio JL, Gavela D (1998) 3D, non-linear coupled, finite element model of thermoelectricity. In: 4th European workshop on thermoelectricsPérez-Aparicio JL, Palma R, Taylor RL (2012) Finite element analysis and material sensitivity of Peltier thermoelectric cells coolers. Int J Heat Mass Transf 55:1363–1374Pérez-Aparicio JL, Sosa H (2004) A continuum three-dimensional, fully coupled, dynamic, non-linear finite element formulation for magnetostrictive materials. Smart Mater Struct 13:493–502Perez-Aparicio JL, Sosa H, Palma R (2007) Numerical investigations of field-defect interactions in piezoelectric ceramics. Int J Solids Struct 44:4892–4908Pérez-Aparicio JL, Taylor RL, Gavela D (2007) Finite element analysis of nonlinear fully coupled thermoelectric materials. Comput Mech 40:35–45Qi H, Fang D, Yao Z (1997) FEM analysis of electro-mechanical coupling effect of piezoelectric materials. Comput Mater Sci 8:283–290Pérez-Aparicio JL, Palma R, Abouali-Sánchez S (2014) Complete finite element method analysis of galvanomagnetic and thermomagnetic effects. Appl Therm Eng (submitted)Perez-Aparicio JL, Palma R, Moreno-Navarro P (2014) Elasto-thermoelectric non-linear, fully coupled, and dynamic finite element analysis of pulsed thermoelectrics. Appl Therm Eng (submitted)Ramírez F, Heyliger PR, Pan E (2006) Free vibration response of two-dimensional magneto-electro-elastic laminated plates. J Sound Vib 292:626–644Reitz JR, Milford FJ (1960) Foundations of electromagnetic theory. Addison-Wesley, BostonReng Z, Ionescu B, Besbes M, Razek A (1995) Calculation of mechanical deformation of magnetic materials in electromagnetic devices. IEEE Trans Magn 31(3):1873–1876Restuccia L (2010) On a thermodynamic theory for magnetic relaxation phenomena due to n microscopic phenomena described by n internal variables. J Non-Equilib Thermodyn 35:379–413Restuccia L, Kluitenberg GA (1988) On generalizations of the Debye equation for dielectric relaxation. Phys A 154:157–182Restuccia L, Kluitenberg GA (1992) On the heat dissipation function for dielectric relaxation phenomena in anisotropic media. Int J Eng Sci 30(3):305–315Riffat SB, Ma X (2003) Thermoelectrics: a review of present and potential applications. Appl Therm Eng 23:913–935Rinaldi C, Brenner H (2002) Body versus surface forces in continuum mechanics: is the Maxwell stress tensor a physically objective Cauchy stress? Phys Rev E 65:036615Rowe DM (ed) (1995) CRC handbook of thermoelectrics. CRC Press, UKRus G, Palma R, Pérez-Aparicio JL (2009) Optimal measurement setup for damage detection in piezoelectric plates. Int J Eng Sci 47:554–572Rus G, Palma R, Pérez-Aparicio JL (2012) Experimental design of dynamic model-based damage identification in piezoelectric ceramics. Mech Syst Signal Process 26:268–293Sadiku MNO (2001) Numerical techniques in electromagnetics. CRC Press LLC, Boca RatonSemenov AS, Kessler H, Liskowsky A, Balke H (2006) On a vector potential formulation for 3D electromechanical finite element analysis. Commun Numer Methods Eng 22:357–375Serra E, Bonaldi M (2008) A finite element formulation for thermoelastic damping analysis. Int J Numer Methods Eng 78(6):671–691Several. Wikipedia. Wikipedia: The Free Encyclopedia, SeveralSoh AK, Liu JX (2005) On the constitutive equations of magnetoelectroelastic solids. J Intell Mater Syst Struct 16:597–602Stefanescu DM (2011) Handbook of force transducers: principles and components. Springer, BerlinTamma KK, Namburu RR (1992) An effective finite element modeling/analysis approach for dynamic thermoelasticity due to second sound effects. Comput Mech 9:73–84Tang T, Yu W (2009) Micromechanical modeling of the multiphysical behavior of smart materials using the variational asymptotic method. Smart Mater Struct 18:1–14Taylor RL (2010) FEAP a finite element analysis program: user manual. University of California, Berkeley. http://www.ce.berkeley.edu/feapThurston RN (1994) Warren p. Mason (1900–1986) physicist, engineer, inventor, author, teacher. IEEE Trans Ultrason Ferroelectr Freq Control 41(4):425–434Tian X, Shen Y, Chen C, He T (2006) A direct finite element method study of generalized thermoelastic problems. Int J Solids Struct 43:2050–2063Tinder RF (2008) Tensor properties of solids: phenomenological development of the tensor properties of crystals. Morgan and Claypool, San RafaelTruesdell C (1968) Thermodynamics for beginners, in irreversible aspects of continuum mechanics. Springer, BerlinTzou HS, Ye R (1996) Pyroelectric and thermal strain effects of piezoelectric (PVDF and PZT) devices. Mech Syst Signal Process 10(4):459–469Walser R (1972) Application of pyromagnetic phenomena to radiation detection

The interest of gait markers in the identification of subgroups among fibromyalgia patients

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia.</p> <p>Methods</p> <p>A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments.</p> <p>Results</p> <p>SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ, poor coping and altered affective status.</p> <p>Conclusion</p> <p>Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM.</p

Prenylation Inhibition-Induced Cell Death in Melanoma: Reduced Sensitivity in BRAF Mutant/PTEN Wild-Type Melanoma Cells.

While targeted therapy brought a new era in the treatment of BRAF mutant melanoma, therapeutic options for non-BRAF mutant cases are still limited. In order to explore the antitumor activity of prenylation inhibition we investigated the response to zoledronic acid treatment in thirteen human melanoma cell lines with known BRAF, NRAS and PTEN mutational status. Effect of zoledronic acid on proliferation, clonogenic potential, apoptosis and migration of melanoma cells as well as the activation of downstream elements of the RAS/RAF pathway were investigated in vitro with SRB, TUNEL and PARP cleavage assays and videomicroscopy and immunoblot measurements, respectively. Subcutaneous and spleen-to-liver colonization xenograft mouse models were used to evaluate the influence of zoledronic acid treatment on primary and disseminated tumor growth of melanoma cells in vivo. Zoledronic acid more efficiently decreased short-term in vitro viability in NRAS mutant cells when compared to BRAF mutant and BRAF/NRAS wild-type cells. In line with this finding, following treatment decreased activation of ribosomal protein S6 was found in NRAS mutant cells. Zoledronic acid demonstrated no significant synergism in cell viability inhibition or apoptosis induction with cisplatin or DTIC treatment in vitro. Importantly, zoledronic acid could inhibit clonogenic growth in the majority of melanoma cell lines except in the three BRAF mutant but PTEN wild-type melanoma lines. A similar pattern was observed in apoptosis induction experiments. In vivo zoledronic acid did not inhibit the subcutaneous growth or spleen-to-liver colonization of melanoma cells. Altogether our data demonstrates that prenylation inhibition may be a novel therapeutic approach in NRAS mutant melanoma. Nevertheless, we also demonstrated that therapeutic sensitivity might be influenced by the PTEN status of BRAF mutant melanoma cells. However, further investigations are needed to identify drugs that have appropriate pharmacological properties to efficiently target prenylation in melanoma cells

Silent chromatin at the middle and ends: lessons from yeasts

Eukaryotic centromeres and telomeres are specialized chromosomal regions that share one common characteristic: their underlying DNA sequences are assembled into heritably repressed chromatin. Silent chromatin in budding and fission yeast is composed of fundamentally divergent proteins tat assemble very different chromatin structures. However, the ultimate behaviour of silent chromatin and the pathways that assemble it seem strikingly similar among Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe) and other eukaryotes. Thus, studies in both yeasts have been instrumental in dissecting the mechanisms that establish and maintain silent chromatin in eukaryotes, contributing substantially to our understanding of epigenetic processes. In this review, we discuss current models for the generation of heterochromatic domains at centromeres and telomeres in the two yeast species

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe