Influencia de la longitud de la biela en la eficiencia y biomecánica del pedaleo submáximo

El principal objetivo de este estudio es analizar el efecto de pequeños cambios en la longitud de la biela en el gasto energético y la técnica de pedaleo submáximo. Participaron 12 ciclistas de fondo en carretera bien entrenados, que realizaron pruebas de pedaleo a tres potencias con cadencia estable, utilizando tres longitudes de biela (en orden aleatorio). Sus bicicletas fueron exactamente reproducidas en un ergómetro que medía el torque ejercido sobre la biela izquierda y derecha de forma independiente. Simultáneamente se registró cinemática 2D de la pierna derecha y el gasto energético al pedalear (eficiencia gruesa). Los resultados muestran que los cambios en la longitud de la biela no tuvieron efecto en la eficiencia gruesa, pero sí en las variables biomecánicas. Una biela de mayor longitud provocó una pérdida de eficiencia mecánica y un aumento en la flexión y el rango de movimiento de la cadera y la rodilla, sin cambios en el tobillo. Aunque estos cambios no fueron lo suficientemente importantes para alterar la eficiencia gruesa, sí que podrían tener implicaciones negativas a largo plazo (peor técnica de pedaleo y riesgo de lesión). En conclusión, el efecto de pequeños cambios en la longitud de la biela, que serían asumibles por ciclistas de competición, producen alteraciones en la biomecánica de pedaleo, pero no en su eficiencia gruesa. Futuros estudios deben abordar los efectos a largo plazo de estos cambios.The main purpose of this study was to analyze the effects of small changes in crank length on gross efficiency and pedaling technique during submaximal cycling. Twelve well-trained road cyclists participated. They pedaled at three power outputs and steady cadence with three crank lengths (in a randomized order). Their bicycles were exactly reproduced on an ergometer where crank torque of the left and right legs were independently registered. 2D kinematic of the right leg and energy cost (gross efficiency) were recorded. The results showed that changes in crank length had no effect on the gross efficiency, but had effect on the biomechanical variables. A longer crank caused a decreased in mechanical efficiency and an increase in the flexion and range of movement of the hip and the knee, without changes in the ankle. These alterations were not significant enough to alter the gross efficiency, but they could have negative long-term implications (worse pedaling technique and possible injuries). In conclusion, the small changes in crank arm length which are feasible for competitive cyclists affected cycling biomechanics, but not gross efficiency. Future studies should study long-term effects of these changes.Peer Reviewe

Reference Gene Validation for RT-qPCR in PBMCs from Asthmatic Patients with or without Obesity

Obesity is known to impair the efficacy of glucocorticoid medications for asthma control. Glucocorticoid-induced gene expression studies may be useful to discriminate those obese asthmatic patients who present a poor response to glucocorticoids. The expression of genes of interest is normalized with respect to reference genes (RGs). Ideally, RGs have a stable expression in different samples and are not affected by experimental conditions. The objective of this work was to analyze suitable RGs to study the role of glucocorticoid-induced genes in obese asthmatic patients in further research. The gene expression of eight potential RGs (GUSB, B2M, POLR2A, PPIA, ACTB, GAPDH, HPRT1, and TBP) was assessed with reverse transcription-quantitative polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from asthmatic, obese asthmatic, and healthy individuals. Their stability was analyzed using four different algorithms-BestKeeper, ?Ct, geNorm, and NormFinder. geNorm analysis recommended the use of a minimum of three genes for normalization. Moreover, intergroup variation due to the treatment was calculated by NormFinder, which found that B2M was the gene that was least affected by different treatments. Comprehensive rankings indicated GUSB and HPRT1 as the best RGs for qPCR in PBMCs from healthy and asthmatic subjects, while B2M and PPIA were the best for obese asthmatic subjects. Finally, our results demonstrated that B2M and HPRT1 were the most stable RGs among all groups, whereas ACTB, TBP, and GAPDH were the worst shared ones

Investigation of nitrogen-related acceptor centers in indium selenide by means of photoluminescence: Determination of the hole effective mass

In this work we report on steady-state and time-resolved photoluminescence (PL) measurements in nitrogen doped p-type indium selenide in the 33-210-K temperature range. In samples with low nitrogen concentration the photoluminescence spectrum consists of exciton-related peaks and a band-to-acceptor recombination peak (2.1-μs lifetime) with LO-phonon replica. An ionization energy of 65.5 meV is proposed for the nitrogenrelated acceptor. A long-lived (18 μs) component, which consists of an asymmetric broadband centered around the acceptor peak, has been also detected by means of time-resolved PL. Samples with a higher nitrogen concentration show a PL spectrum that mainly consists of the asymmetric long-lived broadband that can be associated to a complex center. The asymmetric shape of this band is quantitatively accounted for in the framework of the configuration coordinate model for complex centers. Under the assumption that the nitrogen related acceptor is shallow, the Gerlach-Pollman theory allows an estimate of the hole's effective masses

Light-induced transmission nonlinearities in gallium selenide

The intensity of a He–Ne laser (633 nm, 5 mW) transmitted by different GaSe samples is observed to change in correlation with a Nd-yttrium–aluminum–garnet laser pulse (532 nm, 7.8 ns, 3 mJ) which excites them. Such time response has been attributed to a nonlinear optical effect, i.e., a decrease in the refractive index due to the exciton screening by the photogenerated carriers. A calculation of the absorption coefficient and refractive index at different carrier concentrations has led to a reconstruction of transmittance transients which fully agree with the experimental data at different incident intensities and [email protected] ; [email protected] ; [email protected] ; [email protected]

Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19

COVID-19; Critical care; DexamethasoneCOVID-19; Cuidados intensivos; DexametasonaCOVID-19; Cures crítiques; DexametasonaPurpose Dexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. Methods This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. Results A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37–1.97; p < 0.001). Conclusion Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment.This work was supported by Universidad de La Sabana (LFR) and the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC)

Differences in Inflammatory Cytokine Profile in Obesity-Associated Asthma: Effects of Weight Loss

Obesity and asthma are associated with systemic inflammation maintained by mediators released by adipose tissue and lung. This study investigated the inflammatory serum mediator profile in obese subjects (O) (n = 35), non-obese asthma (NOA) patients (n = 14), obese asthmatics (OA) (n = 21) and healthy controls (HC) (n = 33). The effect of weight loss after bariatric surgery (BS) was examined in 10 OA and 31 O subjects. We analyzed serum markers including leptin, adiponectin, TGF-?1, TNFR2, MCP-1, ezrin, YKL-40, ST2, IL-5, IL-9, and IL-18. Compared with HC subjects, the O group showed increased levels of leptin, TGF-?1, TNFR2, MCP-1, ezrin, YKL-40, and ST2; the OA group presented increased levels of MCP-1, ezrin, YKL-40, and IL-18, and the NOA group had increased levels of ezrin, YKL-40, IL-5, and IL-18. The higher adiponectin/leptin ratio in NOA with respect to OA subjects was the only significant difference between the two groups. IL-9 was the only cytokine with significantly higher levels in OA with respect to O subjects. TNFR2, ezrin, MCP-1, and IL-18 concentrations significantly decreased in O subjects after BS. O, OA, and NOA showed distinct patterns of systemic inflammation. Leptin and adiponectin are regulated in asthma by obesity-dependent and-independent mechanisms. Combination of asthma and obesity does not result in significant additive effects on circulating cytokine levels. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose

[EN] Background Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. Methods In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. Results In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). Conclusions Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. Impact Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.We acknowledge the support of the MyCyFAPP Project consortium. We especially thank the participation and the effort of the patients involved in the study and their families. This work was fully funded by the European Union and the Horizon 2020 Research and Innovation Framework Programme (PHC-26-2014 call Self management of health and disease: citizen engagement and mHealth) under grant number 643806.Calvo-Lerma, J.; Roca-Llorens, M.; Boon, M.; Colombo, C.; De Koning, B.; Fornés-Ferrer, V.; Masip, E.... (2021). Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose. Pediatric Research. 89(1):205-210. https://doi.org/10.1038/s41390-020-0860-3S205210891Turck, D. et al. ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis. Clin. Nutr. 35, 557–577 (2016).Borowitz, D., Baker, R. D. & Stallings, V. Consensus report on nutrition for pediatric patients with cystic fibrosis. J. Pediatr. Gastroenterol. Nutr. 35, 246–259 (2002).Fieker., A., Philpott, J. & Armand, M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clin. Exp. Gastroenterol. 4, 55 (2011).Sitrin, M. D. Digestion and Absorption of Carbohydrates and Proteins in the Gastrointestinal System 137–158 (Springer, Dordrecht, 2014).Gelfond, D. et al. Intestinal pH and gastrointestinal transit profiles in cystic fibrosis patients measured by wireless motility capsule. Dig. Dis. Sci. 58, 2275–2281 (2013).Robinson, P. J. et al. Duodenal pH in cystic fibrosis and its relationship to fat malabsorption. Dig. Dis. Sci. 35, 1299–1304 (1990).Hunter, J. E. Studies on effects of dietary fatty acids as related to their position on triglycerides. Lipids 36, 655–668 (2001).Hernell, O., Staggers, J. E. & Carey, M. C. Physical–chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestionin healthy adult human beings. Biochemistry 29, 2041–2056 (1990).Calvo-Lerma, J. et al. A first approach for an evidence-based in vitro method to adjust pancreatic enzyme replacement therapy in cystic fibrosis. PLoS ONE 14, e0212459 (2019).Aburub, A. Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule. Int. J. Pharm. 544, 158–164 (2018).Calvo-Lerma, J. et al. Innovative approach for self-management and social welfare of children with cystic fibrosis in Europe: development, validation and implementation of an mHealth tool (MyCyFAPP). Br. Med. J. Open. 7, e014931 (2017).Calvo-Lerma, J. et al. Clinical validation of an evidence-based method to adjust pancreatic enzyme replacement therapy through a prospective interventional study in paediatric patients with cystitic fibrosis. PLoS ONE 14, e0213216 (2019).Koumantakls, G. & Radciltf, F. J. Estimating fat in feces by near-infrared reflectance spectroscopy. Clin. Chem. 33, 502–506 (1987).Rivero-Marcotegui, A. et al. Water, fat, nitrogen, and sugar content in feces: reference intervals in children. Clin. Chem. 44, 1540–1544 (1998).Korpi-Steiner, N. L. et al. Comparative analysis of fecal fat quantitation via nuclear magnetic resonance spectroscopy (1H NMR) and gravimetry. Clin. Chim. Acta 400, 33–36 (2009).Dorsey, J. et al. Fat malabsorption in cystic fibrosis: comparison of quantitative fat assay and a novel assay using fecal lauric/behenic acid. J. Pediatr. Gastroenterol. Nutr. 50, 441–446 (2010).Proesmans, M. & De Boeck, K. Omeprazole, a proton pump inhibitor, improves residual steatorrhoea in cystic fibrosis patients treated with high dose pancreatic enzymes. Eur. J. Pediatr. 162, 760–763 (2003).Paz-Yépez, C. et al. Influence of particle size and intestinal conditions on in vitro lipid and protein digestibility of walnuts and peanuts. Food Res. Int. 119, 951–959 (2019).Moore, C. G. et al. Recommendations for planning pilot studies in clinical and translational sciences. Clin. Transl. Sci. 4, 332–337 (2011).Fitzpatrick, J. J. & Kazer, M. W. Encyclopedia of Nursing Research 3rd edn, Vol. 440 (Springer, New York, 2011).Isaac, S. & Michael, W. B. Handbook in Research and Evaluation (Educational and Industrial Testing Services, San Diego, 1995).Asensio-Grau, A. et al. Effect of cooking methods and intestinal conditions on lipolysis, proteolysis and xanthophylls bioaccessibility of eggs. J. Funct. Foods 46, 579–586 (2018).Asensio-Grau, A. et al. Fat digestibility in meat products: influence of food structure and gastrointestinal conditions. Int. J. Food Sci. Nutr. 70, 530–539 (2019).Regan, P. T. et al. Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment. Gastroenterology 7, 285–289 (1979).Fallingborg, J. et al. pH‐profile and regional transit times of the normal gut measured by a radiotelemetry device. Aliment. Phamacol. Ther. 3, 605–614 (1989).Fallingborg, J. Intraluminal pH of the human gastrointestinal tract. Dan. Med Bull. 46, 183–196 (1999).Calvo-Lerma, J. et al. In vitro digestion models to assess lipolysis: the impact of the simulated conditions for gastrointestinal pH, bile salts and digestion fluids. Food Res. Int. 125, 108511 (2019).Kalantzi, L. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm. Res. 23, 165–176 (2006).Zelles, L. & Bai, Q. Y. Fractionation of fatty acids derived from soil lipids by solid phase extraction and their quantitative analysis by GC-MS. Soil Biol. Biochem. 25, 495–507 (1993).Fiorentini, G. et al. Effect of lipid sources with different fatty acid profiles on intake, nutrient digestion and ruminal fermentation of feedlot nellore steers. Asian-Australas. J. Anim. Sci. 28, 1583 (2015).Perman, J. A., Modler, S. & Olson, A. C. Role of pH in production of hydrogen from carbohydrates by colonic bacterial flora. Studies in vivo and in vitro. J. Clin. Invest. 67, 643–650 (1981).Sellin, J. H. & Hart, R. Glucose malabsorption associated with rapid intestinal transit. Am. J. Gastroenterol. 87, 5 (1992).Tran, T. M. D. et al. Effects of a proton-pump inhibitor in cystic fibrosis. Acta Pediatr. 87, 553–558 (1998).Ayoub, F., Lascano, J. & Morelli, G. Proton pump inhibitor use is associated with an increased frequency of hospitalization in patients with cystic fibrosis. Gastroenterol. Res. 10, 288 (2017)

Unraveling the role of protein dynamics in dihydrofolate reductase catalysis

Protein dynamics have controversially been proposed to be at the heart of enzyme catalysis, but identification and analysis of dynamical effects in enzyme-catalyzed reactions have proved very challenging. Here, we tackle this question by comparing an enzyme with its heavy (15N, 13C, 2H substituted) counterpart, providing a subtle probe of dynamics. The crucial hydride transfer step of the reaction (the chemical step) occurs more slowly in the heavy enzyme. A combination of experimental results, quantum mechanics/molecular mechanics simulations, and theoretical analyses identify the origins of the observed differences in reactivity. The generally slightly slower reaction in the heavy enzyme reflects differences in environmental coupling to the hydride transfer step. Importantly, the barrier and contribution of quantum tunneling are not affected, indicating no significant role for “promoting motions” in driving tunneling or modulating the barrier. The chemical step is slower in the heavy enzyme because protein motions coupled to the reaction coordinate are slower. The fact that the heavy enzyme is only slightly less active than its light counterpart shows that protein dynamics have a small, but measurable, effect on the chemical reaction rate

Pressure-induced amorphization of YVO4:Eu3+ nanoboxes

This is an author-created, un-copyedited version of an article published in Nanotechnology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0957-4484/27/2/025701A structural transformation from the zircon-type structure to an amorphous phase has been found in YVO4:Eu3+ nanoboxes at high pressures above 12.7 GPa by means of x-ray diffraction measurements. However, the pair distribution function of the high-pressure phase shows that the local structure of the amorphous phase is similar to the scheelite-type YVO4. These results are confirmed both by Raman spectroscopy and Eu3+ photoluminescence which detect the phase transition to a scheelite-type structure at 10.1 and 9.1 GPa, respectively. The irreversibility of the phase transition is observed with the three techniques after a maximum pressure in the upstroke of around 20 GPa. The existence of two D-5(0)-> F-7(0) photoluminescence peaks confirms the existence of two local environments for Eu3+, at least for the low-pressure phase. One environment is the expected for substituting Y3+ and the other is likely a disordered environment possibly found at the surface of the nanoboxes.This work has been performed under financial support from Spanish MINECO under the National Program of Materials (MAT2013-46649-C4-1/2/3/4-P) and the Consolider-Ingenio 2010 Program (MALTA CSD2007-00045). Funding by the Fundacion Caja Canarias (ENER-01) and the EU-FEDER funds is also acknowledged. JR-F thanks the Alexander von Humboldt Foundation for a postdoctoral fellowship and NS thanks the German Research Foundation (DFG) for financial support (Project RA2585/1-1). We acknowledge Diamond Light Source for time on beamline I15 under proposals EE3652 and EE6517. Parts of this research were carried out at the light source PETRA III at DESY (Hamburg), a member of the Helmholtz Association (HFG). We would like to thank H-P Liermann and W Morgenroth for assistance in using beamline P02.2.Ruiz Fuertes, J.; Gomis, O.; León Luis, SF.; Schrodt, N.; Manjón Herrera, FJ.; Ray, S.; Santamaría Pérez, D.... (2016). Pressure-induced amorphization of YVO4:Eu3+ nanoboxes. Nanotechnology. 27(2):025701-1-025701-8. https://doi.org/10.1088/0957-4484/27/2/025701S025701-1025701-8272Piot, L., Le Floch, S., Cornier, T., Daniele, S., & Machon, D. (2013). Amorphization in Nanoparticles. The Journal of Physical Chemistry C, 117(21), 11133-11140. doi:10.1021/jp401121cZhang, F. X., Wang, J. W., Lang, M., Zhang, J. M., Ewing, R. C., & Boatner, L. A. (2009). High-pressure phase transitions ofScPO4andYPO4. Physical Review B, 80(18). doi:10.1103/physrevb.80.184114Lacomba-Perales, R., Errandonea, D., Meng, Y., & Bettinelli, M. (2010). High-pressure stability and compressibility ofAPO4(A=La, Nd, Eu, Gd, Er, and Y) orthophosphates: An x-ray diffraction study using synchrotron radiation. Physical Review B, 81(6). doi:10.1103/physrevb.81.064113Yuan, H., Wang, K., Li, S., Tan, X., Li, Q., Yan, T., … Zou., B. (2012). Direct Zircon-to-Scheelite Structural Transformation in YPO4 and YPO4:Eu3+ Nanoparticles Under High Pressure. The Journal of Physical Chemistry C, 116(46), 24837-24844. doi:10.1021/jp3088995Mishra, A. K., Garg, N., Pandey, K. K., Shanavas, K. V., Tyagi, A. K., & Sharma, S. M. (2010). Zircon-monoclinic-scheelite transformation in nanocrystalline chromates. Physical Review B, 81(10). doi:10.1103/physrevb.81.104109Wang, L., Yang, W., Ding, Y., Ren, Y., Xiao, S., Liu, B., … Mao, H. (2010). Size-Dependent Amorphization of NanoscaleY2O3at High Pressure. Physical Review Letters, 105(9). doi:10.1103/physrevlett.105.095701Mukherjee, S., Kim, K., & Nair, S. (2007). Short, Highly Ordered, Single-Walled Mixed-Oxide Nanotubes Assemble from Amorphous Nanoparticles. Journal of the American Chemical Society, 129(21), 6820-6826. doi:10.1021/ja070124cŞopu, D., Albe, K., Ritter, Y., & Gleiter, H. (2009). From nanoglasses to bulk massive glasses. Applied Physics Letters, 94(19), 191911. doi:10.1063/1.3130209Ozawa, L., & Itoh, M. (2003). Cathode Ray Tube Phosphors. Chemical Reviews, 103(10), 3835-3856. doi:10.1021/cr0203490Zhu, Y., Xu, W., Zhang, H., Wang, W., Tong, L., Xu, S., … Song, H. (2012). Highly modified spontaneous emissions in YVO4:Eu3+ inverse opal and refractive index sensing application. Applied Physics Letters, 100(8), 081104. doi:10.1063/1.3688167Khan, A. F., Haranath, D., Yadav, R., Singh, S., Chawla, S., & Dutta, V. (2008). Controlled surface distribution and luminescence of YVO4:Eu3+ nanophosphor layers. Applied Physics Letters, 93(7), 073103. doi:10.1063/1.2973163Cho, Y.-S., & Huh, Y.-D. (2011). Preparation of Transparent Red-Emitting YVO4:Eu Nanophosphor Suspensions. Bulletin of the Korean Chemical Society, 32(1), 335-337. doi:10.5012/bkcs.2011.32.1.335Jayaraman, A., Kourouklis, G. A., Espinosa, G. P., Cooper, A. S., & Van Uitert, L. G. (1987). A high-pressure Raman study of yttrium vanadate (YVO4) and the pressure-induced transition from the zircon-type to the scheelite-type structure. Journal of Physics and Chemistry of Solids, 48(8), 755-759. doi:10.1016/0022-3697(87)90072-2Wang, X., Loa, I., Syassen, K., Hanfland, M., & Ferrand, B. (2004). Structural properties of the zircon- and scheelite-type phases ofYVO4at high pressure. Physical Review B, 70(6). doi:10.1103/physrevb.70.064109Manjón, F. J., Rodríguez-Hernández, P., Muñoz, A., Romero, A. H., Errandonea, D., & Syassen, K. (2010). Lattice dynamics ofYVO4at high pressures. Physical Review B, 81(7). doi:10.1103/physrevb.81.075202Boehler, R. (2006). New diamond cell for single-crystal x-ray diffraction. 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(2001). EXPGUI, a graphical user interface forGSAS. Journal of Applied Crystallography, 34(2), 210-213. doi:10.1107/s0021889801002242Qiu, X., Thompson, J. W., & Billinge, S. J. L. (2004). PDFgetX2: a GUI-driven program to obtain the pair distribution function from X-ray powder diffraction data. Journal of Applied Crystallography, 37(4), 678-678. doi:10.1107/s0021889804011744Chupas, P. J., Qiu, X., Hanson, J. C., Lee, P. L., Grey, C. P., & Billinge, S. J. L. (2003). Rapid-acquisition pair distribution function (RA-PDF) analysis. Journal of Applied Crystallography, 36(6), 1342-1347. doi:10.1107/s0021889803017564Farrow, C. L., Juhas, P., Liu, J. W., Bryndin, D., Božin, E. S., Bloch, J., … Billinge, S. J. L. (2007). PDFfit2 and PDFgui: computer programs for studying nanostructure in crystals. Journal of Physics: Condensed Matter, 19(33), 335219. doi:10.1088/0953-8984/19/33/335219Trenque, I., Mornet, S., Duguet, E., & Gaudon, M. (2013). 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Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD