Photo-induced pyridine substitution in cis-[Ru(bpy)(2)(py)(2)]Cl-2 : a snapshot by time-resolved X-ray solution scattering

Determination of transient structures in light-induced processes is a challenging goal for time-resolved techniques. Such techniques are becoming successful in detecting ultrafast structural changes in molecules and do not require the presence of probe-like groups. Here, we demonstrate that TR-WAXS (Time-Resolved Wide Angle X-ray Scattering) can be successfully employed to study the photochemistry of cis-[Ru(bpy)(2)(py)(2)]Cl-2, a mononuclear ruthenium complex of interest in the field of photoactivatable anticancer agents. TR-WAXS is able to detect the release of a pyridine ligand and the coordination of a solvent molecule on a faster timescale than 800 ns of laser excitation. The direct measurement of the photodissociation of pyridine is a major advance in the field of time-resolved techniques allowing detection, for the first time, of the release of a multiatomic ligand formed by low Z atoms. These data demonstrate that TR-WAXS is a powerful technique for studying rapid ligand substitution processes involving photoactive metal complexes of biological interest

Gender diversity in corporate governance and its effect on financial performance: a study on FTSE-MIB listed companies

I examine the presence of women in Italian corporate boards after the inception of the Act 120/2011 by the Italian Government. I considered all the directors of the 40 companies listed in the FTSE – MIB index in 2015 and analyze the implications of gender diversity in corporate boards. Furthermore I study the correlation between gender diversity and financial performance. Different conclusions can be extrapolated from my analysis. My study shows a statistical significance between the presence of female directors in a company and its Return on Asset (ROA) in two different periods. The analysis led to the existence of a statistical significance between ROE and the percentage of female directors in administration boards. Finally I did not find any significant relation between Profit Margin and a diverse board

Protein differences among the Mediterranean species of the genus Spicara.

Protein electrophoresis (PAGE) was used to study the three morphologically different species of Spicara (S. flexuosa, S. maena, S. smaris). Of the 28 enzymatic and additional myogenic loci, five monomorphic loci (LDH-1*, G6PD-1*, PGI-1* and two PMMs*) were species-specific markers of S. smaris with respect to S. flexuosa and S. maena. Four of the 28 enzymatic loci were polymorphic (EST-1*, GLDH*, PEPD*, PGI-2*). Discriminating genetic markers were not identified between S. flexuosa and S. maena. Genetic distance (D) as calculated by Nei’s index (1978), between S. smaris v. S. maena and S. flexuosa showed a value, respectively of D=0·137 and 0·141. Between S. flexuosa and S. maena the value was D=0·006. From the data it can be inferred that S. flexuosa and S. maena are conspecific, despite morphological differences

Fattori biomeccanici di rischio della cifosi giunzionale prossimale

LAUREA SPECIALISTICALe patologie spinali come la scoliosi sono dei disturbi del sistema muscolo‐scheletrico che richiedono un trattamento chirurgico mediante strumentazione vertebrale nei casi di curvature patologiche severe (angolo di Cobb > 40° per la scoliosi) (Weinstein 2001; Morcuende e Weinstein 2003). L’intervento chirurgico mediante strumentazione consiste nella fissazione di barre metalliche lungo la colonna vertebrale grazie all’uso di specifici impianti adeguatamente fissati sulle vertebre: in questo modo si realizza la fusione permanente del rachide allo scopo di ripristinarne la morfologia fisiologica. Sebbene questo tipo di trattamento garantisca una correzione efficace delle curvature spinali patologiche (Weinstein 2001), l’apparizione sintomatica di complicazioni postoperatorie può talvolta richiedere una revisione chirurgica della strumentazione. La prima causa di revisione è la cifosi giunzionale prossimale (CGP) (Schairer, Carrer et al. 2013) la quale ha una prevalenza compresa tra il 20% e il 43% (Yang e Chen 2003; Yagi, King et al. 2012). La CGP si manifesta come un’ipercifosi delle vertebre prossimalmente adiacenti alla strumentazione. Diversi studi sono stati condotti per identificare le cause di questa complicazione chirurgica. I fattori di rischio della CGP includono la dissezione prossimale dei tessuti molli posteriori, la degenerazione della capsula articolare, l’equilibrio sagittale pre- e postoperatorio, la toracoplastica, la qualità del tessuto osseo, l’obesità e la rigidezza della strumentazione (Glattes, Bridwell et al. 2005; Kim, Bridwell et al. 2005; DeWald e Stanley 2006; Kim, Lenke et al. 2007; Yagi, King et al. 2012). Inoltre, è stato constatato che la CGP potrebbe essere associata anche al numero di vertebre strumentate, al tipo di impianto prossimale o più in generale alla configurazione della strumentazione in corrispondenza dell’ultima vertebra strumentata. I patomeccanismi della CGP restano tuttavia controversi. Infatti, le conclusioni presenti in letteratura sono talvolta contraddittorie e non riescono a isolare l’effetto specifico di una data variabile chirurgica rispetto alla CGP. Inoltre, nessun studio biomeccanico ha mai esaminato l’impatto biomeccanico di diverse variabili chirurgiche spinali rispetto agli indici geometrico‐meccanici legati alla CGP. L’obiettivo di questo progetto di ricerca è stato dunque di sviluppare un modello biomeccanico della chirurgia di strumentazione spinale al fine d’analizzare e comprendere i patomeccanismi postoperatori del segmento giunzionale prossimale del rachide. Sei variabili chirurgiche potenzialmente associate all’aumento del rischio d’apparizione della CGP sono state quindi analizzate. Per raggiungere questo obiettivo è stato sviluppato un modello multicorpo che simula numericamente le strumentazioni chirurgiche di sei pazienti adulti affetti da CGP. Per ognuno di questi sei casi, la geometria tridimensionale del rachide è stata ricostruita a partire da due radiografie preoperatorie biplanari e calibrate. In questi modelli ogni vertebra è considerata come un corpo rigido connesso ai livelli adiacenti mediante dei giunti elastici intervertebrali i cui valori di rigidezza sono stati inizialmente ottenuti dalla letteratura e in seguito personalizzati per ogni paziente. La rigidezza della connessione tra gli impianti e l’osso è stata invece modellizzata utilizzando dei dati ottenuti in vitro. Rispetto alle condizioni al contorno del modello, sono state aggiunti prossimalmente degli elementi elastici che modellizzano l’azione dei muscoli estensori; il bacino è stato invece incastrato. I modelli preoperatori così sviluppati sono stati validati comparando i risultati chirurgici reali con quelli ottenuti simulando le stesse procedure chirurgiche effettivamente eseguite per ogni paziente. Per ogni caso della coorte, 384 simulazioni supplementari sono state in seguito eseguite con lo scopo di studiare l’influenza di sei fattori biomeccanici sulla CGP. Sono stati testati quattro differenti procedure di dissezione prossimale, tre tipi d’impianti utilizzati sull’ultima vertebra strumentata, quattro curvature sagittali preparatorie della barre, due diametri prossimali delle barre, due livelli scelti quali ultima vertebra strumentata così come due equilibri sagittali postoperatori. Quattro variabili di risposta riguardanti il segmento giunzionale prossimale del rachide sono stati analizzati. Essi sono l’angolo giunzionale prossimale, la cifosi toracica T4‐T12 così come la forza e il momento flettenti risultanti sul segmento giunzionale prossimale. La simulazione della faccettectomia bilaterale completa, della dissezione dei legamenti sovra- e interspinoso e della loro combinazione ha aumentato l’angolo giunzionale prossimale (rispettivamente dell’8%, 23% e 42%), la cifosi toracica (3%, 8% e 15%) così come la forza (6%, 15% e 28%) e il momento di flessione (11%, 31% e 58%). Rispetto alle viti peduncolari, l’uso degli uncini trasversi sull’ultima vertebra strumentata ha diminuito la cifosi toracica dell’8% e gli altri tre indici geometrico‐meccanici di circa il 25%. L’utilizzo di barre con un diametro prossimale ridotto da 5.5 mm a 4 mm ha diminuito l’angolo giunzionale prossimale (5%), la forza (5%) e il momento di flessione prossimale (6%) mentre ha aumentato leggermente la cifosi toracica (1%). L’aumento della curvatura sagittale preoperatoria delle barre da 10° a 20°, 30° e 40° ha incrementato l’angolo giunzionale prossimale (del 5%, 10% e 16%), la cifosi toracica (9%, 18% e 27%) così come la forza (4%, 9% e 13%) e il momento di flessione prossimali (7%, 14% e 21%). La strumentazione prossimale del rachide fino al livello inferiore rispetto a quello effettivamente scelto per la chirurgia reale ha aumentato l’angolo giunzionale prossimale (18%), la cifosi toracica (9%), la forza (16%) e il momento di flessione prossimali (25%). Infine, rispetto all’equilibrio sagittale postoperatorio reale, la traslazione dorsale di 20 mm di T1 ha incrementato l’angolo giunzionale prossimale (16%), la cifosi toracica (8%), la forza (37%) e il momento di flessione prossimali (22%). Si può dunque concludere che la conservazione degli elementi osteo‐legamentosi superiori alla strumentazione, l’utilizzo di uncini trasversi sull’ultima vertebra strumentata, la riduzione della curvatura sagittale preoperatoria delle barre, la riduzione del diametro prossimale delle barre, lo spostamento in avanti dell’equilibrio sagittale postoperatorio e l’estensione prossimale della strumentazione hanno diminuito significativamente i quattro indici biomeccanici legati ai patomeccanismi del segmento giunzionale prossimale (p‐value 40° for scoliosis) (Weinstein 2001; Morcuende e Weinstein 2003). Spinal instrumentation is a surgical procedure that stabilizes the spine and fuses vertebrae with implanted devices, such as metallic rods, screws and hooks. Although this treatment allows effective correction of pathological spinal curvatures (Weinstein 2001), the occurrence of postoperative complications can sometimes lead to a revision of the instrumentation. The first cause of revision surgery is the proximal junctional kyphosis (PJK) (Schairer, Carrer et al. 2013), having a prevalence between 20% and 43% (Yang e Chen 2003; Yagi, King et al. 2012). PJK appears as a hyperkyphosis of non‐instrumented proximal vertebrae. Several retrospective studies have been conducted to identify its causes. Risk factors related to PJK occurrence and progression include the proximal dissection of the posterior soft tissues, the joint capsule degeneration, the pre- and postoperative sagittal balance, the thoracoplasty, the bone quality, the obesity and the stiffness of the instrumentation (Glattes, Bridwell et al. 2005; Kim, Bridwell et al. 2005; DeWald e Stanley 2006; Kim, Lenke et al. 2007; Yagi, King et al. 2012). It is also reported that PJK could be associated to the number of instrumented vertebrae, the type of proximal implant or the construct configuration at upper instrumented vertebra. However, pathomechanisms of PJK are still controversial because findings reported in the literature are sometimes contradictory and not able to isolate the effect of a specific variable on PJK. In addition, no computational study has reported the impact of several surgical variables on biomechanical indices related to PJK. The objective of this Master project was therefore to develop a biomechanical model of spinal instrumentation in order to analyze and better understand the postoperative pathomechanisms of proximal junctional spinal segment. Six surgical variables potentially increasing the risk for PJK occurrence have been analyzed. In order to achieve this objective, a flexible multibody model was developed and validated to computationally simulate surgical instrumentations of six adult patients affected by PJK. For each case, the spinal tridimensional geometry was reconstructed using two calibrated preoperative radiographs (postero‐anterior and lateral). In these models, each vertebra was considered as a rigid body and was connected to the adjacent levels by intervertebral flexible joints whose stiffness was obtained from the literature and then customized for each patient. The stiffness of implant‐bone connection was modeled using data from an in vitro study. Regarding the boundary conditions of the model, proximal springs have been included in order to simulate the extensor muscles while the pelvis was fixed. Preoperative models developed in this manner were validated by comparing postoperative radiographic outcomes with postoperative outcomes simulated for each patient‐specific surgery. For each case, 384 additional simulations were then performed to investigate the influence of six biomechanical factors on PJK. We tested four different procedures of proximal resection and dissection, three types of implants at upper instrumented vertebra, four sagittal preoperative rod curvatures, two proximal rod diameters, two levels selected as upper instrumented vertebra and two postoperative sagittal balances. Four biomechanical response variables regarding the proximal junctional spinal segment were analyzed: the proximal junctional angle, the thoracic kyphosis T4‐T12, as well as the force and the bending moment resulting on the proximal junctional spinal segment. Simulation of bilateral complete facetectomy, posterior supraspinous and interspinous ligaments dissections and their combination increased the proximal junctional angle (by 8%, 23% and 42%, respectively), the thoracic kyphosis (3%, 8% and 15%) as well as the flexion force (6%, 15% and 28%) and moment (11%, 31% and 58%) acting on the proximal junctional spinal segment. Compared with screws, the use of transverse process hooks at upper instrumented vertebra decreased the thoracic kyphosis by 8% and the other three biomechanical indices by about 25%. The use of rods with proximal diameter reduced from 5.5 mm to 4 mm decreased the proximal junctional angles (5%), the flexion force (5%) and moment (6%), while it slightly increased thoracic kyphosis (1%). Increasing sagittal rod curvature from 10° to 20°, 30° and 40° increased the proximal junctional angle (by 5%, 10% and 16%), the thoracic kyphosis (9%, 18% and 27%) as well the flexion force (4%, 9% and 13%) and moment (7%, 14% and 21%). By instrumenting the proximal spine one level lower than that selected at surgery, it increased the proximal junctional angle (18%), the thoracic kyphosis (9%), the flexion force (16%) and moment (25%). Lastly, compared to the real postoperative sagittal balance, a posterior balance of 20 mm increased the proximal junctional angle (16%), the thoracic kyphosis (8%), as well as the flexion force (37%) and moment (22%). In conclusion, preserving posterior intervertebral elements above the instrumentation, the use of transverse process hooks at upper instrumented vertebra, reducing the sagittal preoperative rod curvature, the use of tapered transition rods, an anterior translation of the sagittal balance following surgery and the proximal extension of the instrumentation significantly decreased the four biomechanical indices related to the pathomechanisms of proximal junctional spinal segment (ANOVA p‐value < 0.05). Knowledge acquired by this research has therefore helped to better understand the biomechanical risk factors for PJK. In perspective, further refining of the biomechanical model would allow to assess the risks for other proximal junctional complications such as Proximal Junctional Failure

Facteurs biomécaniques de risques de la cyphose jonctionnelle proximale

RÉSUMÉ Les déformations rachidiennes telles que la scoliose sont des pathologies du système musculo-squelettique qui nécessitent un traitement chirurgical d’instrumentation dans les cas de courbures pathologiques sévères (angle de Cobb > 40° pour les cas de scoliose) (Weinstein 2001; Morcuende and Weinstein 2003). Cette intervention d’instrumentation consiste à fixer des implants sur les vertèbres et redresser le rachis à l’aide de tiges métalliques, ce qui mène à la fusion permanente du rachis. Bien que ce traitement permette une correction efficace des courbures pathologiques du rachis (Weinstein 2001), la survenue de complications postopératoires peut parfois entraîner une révision de l’instrumentation. La première cause de révision est la cyphose jonctionnelle proximale (CJP) (Schairer, Carrer et al. 2013), avec une prévalence entre 20% et 43% (Yang and Chen 2003; Yagi, King et al. 2012). La CJP se manifeste comme une hypercyphose des vertèbres adjacentes au-dessus de l'instrumentation. Plusieurs études rétrospectives ont été réalisées afin d’en identifier les causes. Les facteurs de risque associés à la survenue et à la progression de la CJP incluent la dissection proximale des tissus mous postérieurs, la dégénérescence de la capsule articulaire, l’équilibre sagittal pré- et postopératoire, la thoracoplastie, la qualité osseuse, l'obésité et la raideur de l’instrumentation (Glattes, Bridwell et al. 2005; Kim, Bridwell et al. 2005; DeWald and Stanley 2006; Kim, Lenke et al. 2007; Yagi, King et al. 2012). Ainsi, on rapporte que la CJP pourrait être associée au nombre de vertèbres instrumentées, au type d’implant proximal ou de manière plus générale à la configuration de l'instrumentation au niveau de la vertèbre proximale instrumentée. Les pathomécanismes de la CJP demeurent toutefois encore controversés. En effet, les conclusions rapportées dans la littérature sont parfois contradictoires et n’arrivent pas à isoler l’effet spécifique d’une variable donnée par rapport à la CJP. En outre, aucune étude biomécanique n’a rapporté l'impact biomécanique de différentes variables de la chirurgie rachidienne sur les indices géométrico-mécaniques reliés à la CJP. L’objectif de ce projet de maîtrise a donc été de développer un modèle biomécanique de la chirurgie d’instrumentation afin d’analyser et comprendre les pathomécanismes postopératoires du segment jonctionnel proximal du rachis. Six variables chirurgicales pouvant augmenter potentiellement le risque de survenue de la CJP ont ainsi été analysées.----------ABSTRACT Spinal deformities such as scoliosis are a group of musculoskeletal disorders requiring surgical instrumentation in cases of severe pathological curvatures (e.g. Cobb angle > 40° for scoliosis) (Weinstein 2001; Morcuende and Weinstein 2003). Spinal instrumentation is a surgical procedure that stabilizes the spine and fuses vertebrae with implanted devices, such as metallic rods, screws and hooks. Although this treatment allows effective correction of pathological spinal curvatures (Weinstein 2001), the occurrence of postoperative complications can sometimes lead to a revision of the instrumentation. The first cause of revision surgery is the proximal junctional kyphosis (PJK) (Schairer, Carrer et al. 2013), having a prevalence between 20% and 43% (Yang and Chen 2003; Yagi, King et al. 2012). PJK appears as a hyperkyphosis of non instrumented proximal vertebrae. Several retrospective studies have been conducted to identify its causes. Risk factors related to PJK occurrence and progression include the proximal dissection of the posterior soft tissues, the joint capsule degeneration, the pre- and postoperative sagittal balance, the thoracoplasty, the bone quality, the obesity and the stiffness of the instrumentation (Glattes, Bridwell et al. 2005; Kim, Bridwell et al. 2005; DeWald and Stanley 2006; Kim, Lenke et al. 2007; Yagi, King et al. 2012). It is also reported that PJK could be associated to the number of instrumented vertebrae, the type of proximal implant or the construct configuration at upper instrumented vertebra. However, pathomechanisms of PJK are still controversial because findings reported in the literature are sometimes contradictory and not able to isolate the effect of a specific variable on PJK. In addition, no computational study has reported the impact of several surgical variables on biomechanical indices related to PJK. The objective of this Master project was therefore to develop a biomechanical model of spinal instrumentation in order to analyze and better understand the postoperative pathomechanisms of proximal junctional spinal segment. Six surgical variables potentially increasing the risk for PJK occurrence have been analyzed. In order to achieve this objective, a multibody model was developed and validated to computationally simulate surgical instrumentations of six adult patients affected by PJK. For each case, the spinal tridimensional geometry was reconstructed using two calibrated preoperative radiographs (postero-anterior and lateral). In these models, each vertebra wa

Introducing a standard method for experimental determination of the solvent response in laser pump, X-ray probe time-resolved wide-angle X-ray scattering experiments on systems in solution

WOS:000323520600021International audienceIn time-resolved laser pump, X-ray probe wide-angle X-ray scattering experiments on systems in solution the structural response of the system is accompanied by a solvent response. The solvent response is caused by reorganization of the bulk solvent following the laser pump event, and in order to extract the structural information of the solute, the solvent response has to be treated. Methodologies capable of doing so include both theoretical modelling and experimental determination of the solvent response. In the work presented here, we have investigated how to obtain a reproducible solvent response-the solvent term-experimentally when applying laser pump, X-ray probe time-resolved wide-angle X-ray scattering. The solvent term describes difference scattering arising from the structural response of the solvent to changes in the hydrodynamic parameters: pressure, temperature and density. We present results based on NIR and dye mediated solvent heating, and demonstrate that the solvent response is independent of the heating method. The NIR heating is shown to be rendered unusable by higher order effects under certain experimental conditions, while the dye mediated solvent heating is demonstrated to exhibit first order behaviour with respect to the amount of energy deposited in the solution. We introduce a standardized method for recording solvent responses in laser pump, X-ray probe time-resolved X-ray wide-angle scattering experiments by using dye mediated solvent heating. Furthermore, we have generated a library of solvent terms, which can be used to describe the solvent term in any TRWAXS experiment, and made it available online

Tilting refractive x-ray lenses for fine-tuning their focal length

In this work, we measure and model tilted x-ray refractive lenses to investigate their effects on an x-ray beam. The modelling is benchmarked against at-wavelength metrology obtained with x-ray speckle vector tracking experiments (XSVT) at the BM05 beamline at the ESRF-EBS light source, showing very good agreement. This validation permits us to explore possible applications of tilted x-ray lenses in optical design: we demonstrate that tilting 1D lenses around their focusing direction can be used for fine-tuning their focal length with possible applications in beamline optical design.Comment: 15 pages, 13 figures, 38 references to be submitted to Optics Expres

High pressure X-Ray Photon Correlation Spectroscopy at 4th generation synchrotron sources

A new experimental setup combining X-Ray Photon Correlation Spectroscopy (XPCS) in the hard x-ray regime and a high-pressure sample environment is developed to monitor the pressure dependence of the internal motion of complex systems down to the atomic scale in the multi-GPa range, from room temperature to 600K. The high flux of coherent high energy x-rays at 4th generation synchrotron source solves the problems caused by the absorption of the Diamond Anvil Cells used to generate the high pressure, enabling the measurement of the intermediate scattering function over 6 orders of magnitude in time, from $10^{-3}$ s to $10^{3}$s. The constraints posed by the high-pressure generation such as the preservation of the x-ray's coherence, as well as the sample, pressure and temperature stability are discussed, and the feasibility of high pressure XPCS is demonstrated through results obtained on metallic glasses