Evaluation of outcome of posterior decompression and instrumented fusion in thoracolumbar fractures

Background: The fractures of the thoracolumbar junction are the most common injuries of the vertebral column. Fall from a height and road traffic accidents are the main causes of injury. The present study aims to evaluate the functional, neurological and radiological outcome of the posterior decompression and instrumented fusion in operated patients with thoracolumbar fractures.Methods: In this retrospective and prospective study, a cohort of 30 patients with thoracolumbar fractures, classified by thoracolumbar injury classification and severity (TLICS) scoring system, underwent posterior decompression and pedicle screw fixation from January 2013 to August 2018 were included. Patients were assessed functionally (ODI score), neurologically (MRC grading) and radiologically (kyphotic angle) preoperatively and at 6 weeks, 3 months, 6 months and 12 months post-operatively.Results: The mean ODI score improved from 87.40 pre-operatively to 13.33 at final follow-up (p value 0.001). The mean kyphotic angle decreased from 24.37 degrees preoperatively to 9.87 degrees postoperatively (p value 0.001) with mean loss of correction of 1.16 degrees at final follow-up. Hip flexors and knee extensors improved from a mean preoperative value of 2.60 to 4.83 at final follow-up (p value 0.001). Similarly, ankle dorsiflexors, long toe extensors and ankle plantar flexors improved from mean preoperative value of 2.53, 2.50 and 2.60 to 3.93, 3.80 and 4.73 at final follow-up, respectively (p value 0.001).Conclusions: Posterior decompression and instrumented fusion is a safe and effective surgical option in patients with thoracolumbar fractures. TLICS scoring system has a prognostic value and helps in determining the prognosis in these patients

Effects of Helicobacter pylori Vacuolating Cytotoxin A on intracellular calcium signalling in T-lymphocytes

More than 50% of the world's population harbor Helicobacter pylori in their stomach mucosa. The chronic gastric infection is associated with several diseases including peptic ulcer disease and gastric carcinoma. One of the most thoroughly studied virulence factors produced by H. pylori is the Vacuolating Cytotoxin A (VacA). All isolated H. pylori strains possess the vacA gene, although significant sequence diversity was noticed in vacA genes across H. pylori isolates. VacA protein is produced and secreted as an 88 kD mature toxin. The protein binds to the host cells and is internalized. Inside the host cells, it causes “vacuole”-like membrane vesicles in the cytoplasm of gastric epithelial cells. Besides vacuolation, VacA exerts various other effects on target cells. VacA also forms membrane-embedded pores at the inner-mitochondrial membrane, resulting in mitochondrial dysfunction by cytochrome c release and apoptosis induction. VacA suppresses nuclear translocation of nuclear factor of activated T-cells (NFAT) resulting in down regulation of interleukin-2 (IL2) gene transcription to efficiently block proliferation of T-cells. The aim of this work was to understand the effects of VacA on intracellular calcium signalling in T-lymphocytes by considering the fact that VacA inhibits the Ca2+-calmodulin-dependent phosphatase calcineurin and induces cell cycle arrest. However, the exact mechanism how VacA exerts this response in T-cells is not known. Therefore, in this thesis various cell lines were used to study the effects of VacA on calcium influx. Calcium influx was found to be affected in the presence of VacA protein in the human Jurkat E6.1 T-cell line and primary human CD4+ T-cells activated by phorbol myristate acetate (PMA). Once inside T-cells, it could be shown that VacA suppresses the increase of the cytosolic free calcium concentration after stimulation by the calcium ionophore ionomycin and thapsigargin. Ionomycin forms pores in the cytoplasmic membrane, whereas thapsigargin blocks the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) and thereby causes depletion of the endoplasmic reticulum (ER) calcium store. In contrast, a VacA mutant, which was constructed by deletion of the hydrophobic region (amino acids 6-27), was unable to induce vacuolation activity and to block Ca2+ influx. A major result of this work was to demonstrate that one of the main components of store operated calcium entry (SOCE), the ER localized calcium sensor protein STIM1, is a target of VacA. Using co-localization studies and yeast two-hybrid (YTH) assays, it was found that VacA localizes to the lumen of the ER where it binds to the cEF-hand domain of STIM1. Furthermore, these data show that VacA strongly reduced the movements of the STIM1 towards the plasma membrane localized calcium channel ORAI1 after Ca2+ store depletion by thapsigargin. A YTH screen identified cEF-hand domain of STIM1 as the target of VacA to inhibit calcium influx. The results obtained in this work showing involvement of VacA in the modulation of intracellular calcium signalling will provide new insights that are required to understand how VacA inhibits T-cell proliferation and signalling.Mehr als 50% der Weltbevölkerung tragen Helicobacter pylori in ihrem Magenepithel. H. pylori kolonisiert dauerhaft die Magenschleimhaut und ist mit verschiedenen Erkrankungen wie Magen- oder Zwölffingerdarmgeschwüren sowie Magenkrebs assoziiert. Einer der am besten untersuchten Virulenzfaktoren von H. pylori ist das vakuolisierende Cytotoxin VacA. Alle H. pylori-Isolate haben ein vacA-Gen, wobei allerdings deutliche Sequenzvariationen zwischen verschiedenen Stämmen auftreten. Das VacA-Protein wird als Vorläuferprotein produziert und als reifes Toxin von 88 kDa sekretiert. Das reife Protein bindet an Wirtszellen und wird von diesen internalisiert. In der Zielzelle verursacht es die Bildung vakuolenartiger Membranvesikel im Zytoplasma. Unabhängig von dieser Vakuolisierung hat VacA verschiedene weitere Effekte auf Zielzellen. So bildet es Poren in der inneren Mitochondrienmembran, die zu einer Mitochondrien-Fehlfunktion mit Cytochrom c-Freisetzung und Apoptose-Induktion führen. VacA unterdrückt auch die Translokation des Transkriptionsfaktors NFAT (Nuclear Factor of Activated T-cells) in den Zellkern und damit die Transkription des Interleukin-2 (IL-2)-Gens, was zu einer effizienten Hemmung der T-Zell-Proliferation führt. Ziel dieser Arbeit war die Untersuchung des Einflusses von VacA auf die intrazelluläre Calcium-Signalübertragung in T-Zellen vor dem Hintergrund, dass VacA die Calcium/Calmodulin-abhängige Phosphatase Calcineurin inhibiert und einen Stopp des Zellzyklus induziert. Der genaue Mechanismus dieser Antwort in T-Zellen ist allerdings nicht bekannt. In dieser Arbeit wurden verschiedene Zelllinien zur Untersuchung des Effekts von VacA auf den Calciumeinstrom verwendet. Es konnte nachgewiesen werden, dass der Calciumeinstrom in der humanen T-Zelllinie Jurkat E6.1 und in primären humanen CD4+ T-Zellen nach Aktivierung mit Phorbol-Myristat-Acetat (PMA) durch VacA beeinträchtigt wird. VacA supprimiert auch den Anstieg der freien Calcium-Konzentration im Cytosol nach Stimulierung mit den Calcium-Ionophoren Ionomycin und Thapsigargin. Ionomycin bildet Poren in der Cytoplasmamembran, während Thapsigargin die ATPase SERCA (sarcoplasmic/endoplasmic reticulum calcium ATPase) blockiert und dadurch eine Calcium-Depletion im endoplasmatischen Reticulum (ER) verursacht. Im Gegensatz zu VacA war eine rekombinante VacA-Variante, die durch Deletion einer hydrophoben Region (Aminosäuren 6-27) hergestellt wurde, nicht in der Lage, eine Vakuolisierung zu indúzieren und den Calciumeinstrom zu blockieren. Ein wichtiges Ergebnis dieser Arbeit war es zu zeigen dass eine der Hauptkomponenten der Calciumaufnahme (Store-Operated Calcium Entry, SOCE), das ER-lokalisierte Calcium-Sensorprotein STIM1, als Zielmolekül für VacA dient. Mittels Kolokalisationsstudien und einem Yeast Two-Hybrid-Verfahren (YTH) konnte gezeigt werden, dass VacA im ER-Lumen lokalisiert ist und mit der calciumbindenden (EF-hand) –Domäne von STIM1 interagiert. Der Transport von STIM1 zur Plasmamembran und zu dem dort lokalisierten Calciumkanal ORAI1 ist nach Calciumdepletion mit Thapsigargin in Gegenwart von VacA deutlich reduziert. Mittels eines YTH Screens konnte die EF-hand-Domäne von STIM1 als Interaktionspartner von VacA identifiziert werden. Die im Rahmen dieser Arbeit beobachtete Aktivität von VacA bei der Modulation der intrazellulären Calcium-Signaltransduktion liefert damit neue Erkenntnisse, die für ein genaueres Verständnis der durch VacA hervorgerufenen Inhibition der T-Zell-Proliferation und Signaltransduktion notwendig sind

Explaining Drift using Shapley Values

Machine learning models often deteriorate in their performance when they are used to predict the outcomes over data on which they were not trained. These scenarios can often arise in real world when the distribution of data changes gradually or abruptly due to major events like a pandemic. There have been many attempts in machine learning research to come up with techniques that are resilient to such Concept drifts. However, there is no principled framework to identify the drivers behind the drift in model performance. In this paper, we propose a novel framework - DBShap that uses Shapley values to identify the main contributors of the drift and quantify their respective contributions. The proposed framework not only quantifies the importance of individual features in driving the drift but also includes the change in the underlying relation between the input and output as a possible driver. The explanation provided by DBShap can be used to understand the root cause behind the drift and use it to make the model resilient to the drift

Total-internal-reflection deflectometry for measuring small deflections of a fluid surface

We describe a method that uses total internal reflection at the water-air interface inside a large, transparent tank, to measure the interface's deflections. Using this configuration, we obtain an optical set-up where the liquid surface acts as a deformable mirror. The set-up is shown to be extremely sensitive to very small disturbances of the reflecting water surface, which are detected by means of visualising the reflections of a reference pattern. When the water surface is deformed, it reflects a distorted image of the reference pattern, similar to a synthetic Schlieren set-up. The distortions of the pattern are analysed using a suitable image correlation method. The displacement fields thus obtained correlate to the local spatial gradients of the water surface. The gradient fields are integrated in a least-squares sense to obtain a full instantaneous reconstruction of the water surface. This method is particularly useful when a solid object is placed just above water surface, whose presence makes the liquid surface otherwise optically inaccessible.Comment: 14 pages, 5 figures. Sample images and processing code in `ancillary files' director

Air entrapment and its effect on pressure impulses in the slamming of a flat disc on water

The presence of ambient air in liquid-slamming events plays a crucial role in influencing the shape of the liquid surface prior to the impact, and the distribution of loads created upon impact. We study the effect of trapped air on impact loads in a simplified geometry, by slamming a horizontal flat disc onto a stationary water bath at a well-controlled velocity. We show how air trapping influences pressure peaks at different radial locations on the disc, how the pressure impulses are affected and how local pressure impulses differ from those obtained from area-integrated (force) impulses at impact. More specifically, we find that the air layer causes a gradual buildup of the load before the peak value is reached, and show that this buildup follows inertial scaling. Further, the same localised pressure impulse at the disc centre is found to be lower than the corresponding (area-integrated) force impulse on the entire disc. While the (area-integrated) force impulses are close to the classical result of Batchelor (An Introduction to Fluid Dynamics, Cambridge University Press, 1967, § 6.10) and Glasheen & McMahon (Phys. Fluids, vol. 8, issue 8, 1996, pp. 2078-2083), the localised pressure impulses at the disc centre, where the trapped air layer is at its thickest, lie closer to the theoretical estimation by Peters et al. (J. Fluid Mech., vol. 724, 2013, pp. 553-580) for an air-cushioned impact.We acknowledge financial support from SLING (project number P14-10.1), which is partly financed by the Netherlands Organisation for Scientific Research (NWO). P.V.-M. acknowledges the support of the Spanish Ministry of Economy and Competitiveness through grants DPI2017-88201-C3-3-R and DPI2018-102829-REDT, partly funded with European funds

Air-cushioning below an impacting wave-structured disk:Free-surface deformation and slamming load

Prior to the impact of a horizontal disk onto a liquid surface, the air underneath flows radially outward across the liquid surface to escape from below the edge of the disk. Such airflow causes the surface to be elevated near the disk edge, creating a free-surface condition that influences the details of the subsequent impact dynamics. In this work, the nature of the surface elevation under an impacting disk is investigated by modulating the forcing of the free surface: The airflow below the disk is altered by imposing a radially symmetric wave structure of varying wavelength on the impacting disk surface. Subsequently, the liquid surface deformation before impact is measured experimentally using a total internal reflection technique. The experiments provide convincing evidence that supports the argument that the surface elevation is an instability of the Kelvin-Helmholtz type. In addition, the impact force exerted on the wave-structured disks is measured using a load cell. Due to the macroscopic wave structure on the disk, the maximum impact force is significantly reduced, and the results indicate that both the free-surface deformation before impact and the way in which the impacting surface is subsequently wetted influence the maximum impact force.</p

Blessing Nonvital Tooth with Life through Revascularization

In recent times, revascularization has been found to be a better&nbsp;alternative in treatment of immature, nonvital tooth with blunderbuss&nbsp;canal since, it enables formation of root apex radiographically&nbsp;which allows the clinician to get a better hermeatic&nbsp;seal in the apical area. Success of the treatment also dependsgreatly upon the disinfection of the canal, which is achieved&nbsp;not only by the use of intracanal irrigants, but also with the use&nbsp;of intracanal medicaments like triple antibiotic paste, which is&nbsp;followed by getting a good coronal seal to prevent orthograde&nbsp;infection during the procedure. However, long-term prognosisof the treatment and the tissue occupying the canal space&nbsp;requires further investigatio

On wedge-slamming pressures

The water entry of a wedge has become a model test in marine and naval engineering research. Wagner theory, originating in 1932, predicts impact pressures, and accounts for contributions to the total pressure arising from various flow domains in the vicinity of the wetting region on the wedge. Here we study the slamming of a wedge and a cone at a constant, well-controlled velocity throughout the impact event using high fidelity sensors. Pressures at two locations on the impactor are measured during and after impact. Pressure time series from the two impactors are discussed using inertial pressure and time scales. The non-dimensionalised pressure time series are compared to sensor-integrated averaged composite Wagner solutions (Zhao & Faltinsen 1993), Logvinovich (1969, 4.7), modified Logvinovich (Korobkin & Malenica 2005) and generalised Wagner models (Korobkin 2004). In addition, we provide an independent experimental justification of approximations made in the literature in extending the Wagner model to three-dimensions. The second part of the paper deals with pre-impact air cushioning -- an important concern since it is responsible for determining the thickness of air layer trapped upon impact. Using a custom-made technique we measure the air-water interface dynamics as it responds to the build up of pressure in the air layer intervening in between the impactor and the free surface. We show both experimentally and using two-fluid boundary integral (BI) simulations, that the pre-impact deflection of the interface due to air-cushioning is fully described by potential flow.Comment: 36 pages, 18 figures (including appendices). 5 movies and 1 supplementary text pdf in ancillary file