La maladie liée aux IgG4 : une cause possible d'ictère obstructif

La maladie liée aux immunoglobulines de type G4 (ML-IgG4) est reconnue depuis le début des années 2000 comme une entité regroupant un ensemble de maladies inflammatoires à caractéristiques histopathologiques communes. Pouvant atteindre quasiment tous les organes et tissus, elle se manifeste le plus souvent de manière subaiguë chez des hommes de plus de 50 ans, sous forme de masse ou d'agrandissement diffus des organes atteints. L'aspect histopathologique est celui d'une infiltration lymphoplasmocytaire à prédominance de plasmocytes IgG4 positifs et d'une fibrose progressive. Ses caractéristiques cliniques et radiologiques peuvent rendre difficile la distinction avec un processus tumoral. La maladie répond bien à un traitement systémique de glucocorticoïdes, avec toutefois un haut taux de récidives après l'arrêt du traitement. Immunoglobulin G4 related disease (IgG4-RD) has been recognized since early 2000s as an entity comprising a set of inflammatory diseases with common histopathological features. The disease may affect almost all organs and tissues, and often occurs in a subacute fashion in males over 50 years as a mass or diffuse enlargement of affected organs. The histopathological appearance is characterized by a lymphoplasmacytic infiltration with predominantly IgG4-positive plasma cells and progressive fibrosis. Its clinical and radiological features can make the distinction with a malignancy difficult. The disease responds well to systemic glucocorticoids however with a high rate of recurrence after treatment discontinuation.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Delayed presentation of deep penetrating trauma to the subaxial cervical spine.

PURPOSE: To present a rare case of deep penetrating neck trauma in which a retained foreign body in the cervical spine (a broken knife blade) resulted in delayed radicular injury. We describe the surgical management using a retrojugular approach. CASE REPORT: Our patient sustained a stab wound to the supraclavicular triangle from a small pocketknife. He was initially managed in a local hospital by simple primary wound closure without any radiological examinations, and was discharged home. The patient re-consulted in a delayed fashion with mild local persistent neck pain. Subsequent radiological investigations revealed a foreign body (the broken blade of a pocket knife) embedded in the left neural foramen between the C6 and C7 vertebrae penetrating the disc space. The blade was lying between the left C7 nerve root and the ipsilateral vertebral artery (VA) at the transition of V1 and V2 segments. Initial neurological evaluation was normal. Some days later, the patient developed a delayed left C7 radicular deficit. We undertook urgent exploration along the wound corridor through a retrojugular, transforaminal approach with successful removal of the blade. DISCUSSION: To our knowledge, this is a unique case where a retained foreign body penetrated the soft tissues of the neck, embedding deep in the vertebral column without vascular, aerodigestive or significant primary neurological injury, while causing delayed neck pain and delayed onset radicular injury. We describe our surgical management for removal of the retained blade. The retrojugular approach gives excellent access to all of the important anatomical structures of the neck from an anterolateral approach.

La maladie liée aux IgG4: une cause possible d'ictère obstructif [IgG4-related disease: a possible cause of obstructive jaundice].

Immunoglobulin G4 related disease (IgG4-RD) has been recognized since early 2000s as an entity comprising a set of inflammatory diseases with common histopathological features. The disease may affect almost all organs and tissues, and often occurs in a subacute fashion in males over 50 years as a mass or diffuse enlargement of affected organs. The histopathological appearance is characterized by a lymphoplasmacytic infiltration with predominantly IgG4-positive plasma cells and progressive fibrosis. Its clinical and radiological features can make the distinction with a malignancy difficult. The disease responds well to systemic glucocorticoids however with a high rate of recurrence after treatment discontinuation.

Label-free detection of tobramycin in serum by transmission-localized surface plasmon resonance.

In order to improve the efficacy and safety of treatments, drug dosage needs to be adjusted to the actual needs of each patient in a truly personalized medicine approach. Key for widespread dosage adjustment is the availability of point-of-care devices able to measure plasma drug concentration in a simple, automated, and cost-effective fashion. In the present work, we introduce and test a portable, palm-sized transmission-localized surface plasmon resonance (T-LSPR) setup, comprised of off-the-shelf components and coupled with DNA-based aptamers specific to the antibiotic tobramycin (467 Da). The core of the T-LSPR setup are aptamer-functionalized gold nanoislands (NIs) deposited on a glass slide covered with fluorine-doped tin oxide (FTO), which acts as a biosensor. The gold NIs exhibit localized plasmon resonance in the visible range matching the sensitivity of the complementary metal oxide semiconductor (CMOS) image sensor employed as a light detector. The combination of gold NIs on the FTO substrate, causing NIs size and pattern irregularity, might reduce the overall sensitivity but confers extremely high stability in high-ionic solutions, allowing it to withstand numerous regeneration cycles without sensing losses. With this rather simple T-LSPR setup, we show real-time label-free detection of tobramycin in buffer, measuring concentrations down to 0.5 μM. We determined an affinity constant of the aptamer-tobramycin pair consistent with the value obtained using a commercial propagating-wave based SPR. Moreover, our label-free system can detect tobramycin in filtered undiluted blood serum, measuring concentrations down to 10 μM with a theoretical detection limit of 3.4 μM. While the association signal of tobramycin onto the aptamer is masked by the serum injection, the quantification of the captured tobramycin is possible during the dissociation phase and leads to a linear calibration curve for the concentrations over the tested range (10-80 μM). The plasmon shift following surface binding is calculated in terms of both plasmon peak location and hue, with the latter allowing faster data elaboration and real-time display of the results. The presented T-LSPR system shows for the first time label-free direct detection and quantification of a small molecule in the complex matrix of filtered undiluted blood serum. Its uncomplicated construction and compact size, together with the remarkable performances, represent a leap forward toward effective point-of-care devices for therapeutic drug concentration monitoring.

Wavelet Analysis in Turbulence

The objective of this thesis is to study wavelets and their role in turbulence applications. Under scrutiny in the thesis is the intermittency in turbulence models. Wavelets are used as a mathematical tool to study the intermittent activities that turbulence models produce. The first section generally introduces wavelets and wavelet transforms as a mathematical tool. Moreover, the basic properties of turbulence are discussed and classical methods for modeling turbulent flows are explained. Wavelets are implemented to model the turbulence as well as to analyze turbulent signals. The model studied here is the GOY (Gledzer 1973, Ohkitani & Yamada 1989) shell model of turbulence, which is a popular model for explaining intermittency based on the cascade of kinetic energy. The goal is to introduce better quantification method for intermittency obtained in a shell model. Wavelets are localized in both space (time) and scale, therefore, they are suitable candidates for the study of singular bursts, that interrupt the calm periods of an energy flow through various scales. The study concerns two questions, namely the frequency of the occurrence as well as the intensity of the singular bursts at various Reynolds numbers. The results gave an insight that singularities become more local as Reynolds number increases. The singularities become more local also when the shell number is increased at certain Reynolds number. The study revealed that the singular bursts are more frequent at Re ~ 107 than other cases with lower Re. The intermittency of bursts for the cases with Re ~ 106 and Re ~ 105 was similar, but for the case with Re ~ 104 bursts occured after long waiting time in a different fashion so that it could not be scaled with higher Re.

Value and Prices in Russian Economic Thought: A journey inside the Russian Synthesis, 1890-1920

This book explores Russian synthesis that occurred in Russian economic thought between 1890 and 1920. This includes all the attempts at synthesis between classical political economy and marginalism; the labour theory of value and marginal utility; and value and prices. The various ways in which Russian economists have approached these issues have generally been addressed in a piecemeal fashion in history of economic thought literature. This book returns to the primary sources in the Russian language, translating many into English for the first time, and offers the first comprehensive history of the Russian synthesis. The book first examines the origins of the Russian synthesis by determining the condition of reception in Russia of the various theories of value involved: the classical theories of value of Ricardo and Marx on one side; the marginalist theories of prices of Menger, Walras and Jevons on the other. It then reconstructs the three generations of the Russian synthesis: the first (Tugan-Baranovsky), the second, the mathematicians (Dmitriev, Bortkiewicz, Shaposhnikov, Slutsky, etc.) and the last (Yurovsky), with an emphasis on Tugan-Baranovsky's initial impetus. This volume is suitable for those studying economic theory and philosophy as well as those interested in the history of economic thought.

Integrative and systemic approaches for evaluating PPARβ/δ (PPARD) function.

The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of genes involved in cellular differentiation, development, metabolism and also tumorigenesis. Three PPAR isotypes (α, β/δ and γ) have been identified, among which PPARβ/δ is the most difficult to functionally examine due to its tissue-specific diversity in cell fate determination, energy metabolism and housekeeping activities. PPARβ/δ acts both in a ligand-dependent and -independent manner. The specific type of regulation, activation or repression, is determined by many factors, among which the type of ligand, the presence/absence of PPARβ/δ-interacting corepressor or coactivator complexes and PPARβ/δ protein post-translational modifications play major roles. Recently, new global approaches to the study of nuclear receptors have made it possible to evaluate their molecular activity in a more systemic fashion, rather than deeply digging into a single pathway/function. This systemic approach is ideally suited for studying PPARβ/δ, due to its ubiquitous expression in various organs and its overlapping and tissue-specific transcriptomic signatures. The aim of the present review is to present in detail the diversity of PPARβ/δ function, focusing on the different information gained at the systemic level, and describing the global and unbiased approaches that combine a systems view with molecular understanding.

Cardiogene: an innovative multidisciplinary consultation for genetic arrhythmias

Introduction: Over the past decade clinically relevant progress has been made regarding the genetic origin of sudden cardiac death due to arrhythmic syndromes such as congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholinergic polymorphic ventricular tachycardia (CPVT) and short QT (SQTS). An increased number of patients are diagnosed and their offspring sent for screening. In order to optimize care of these families we have set up a multidisciplinary consultation, "Cardiogene", consisting of a pediatric and an adult cardiologist and a clinical geneticist. All families are seen at a common consult in order to take the family history, genetic background and to explain the disease to patients and their families. Appropriate cardiac investigations and genetic testing are then performed and the families seen again in a multidisciplinary fashion for the results. We have reviewed all our cases over the past 5 years. Methods: retrospective review of all cases seen at Cardiogene Clinic for suspicion of arrhythmic syndromes since 2007. Results: 23 families were seen at the Cardiogene Clinic with a total of 41 children. The suspected arrhythmic syndrome was LQTS in 14 families (26 children), BrS in 7 families (14 children), SQTS in1 family (2 children) and CPVT in 1 family (3 children). Of the 41 children 17 were genetically positive for an arrhythmic syndrome: 14 were for LQTS, 3 for BrS. 24 children were genetically negative however 4 of those were phenotypically positive: 2 LQTS, 1 BrS and 1 CPVT. In 3 families the diagnosis was initially made in a child and then found in the parent. In 2 families the diagnosis was made after a sudden death of one of their children, 1 LQTS (3 week old child), 1 BrS (20 year old). Discussion: Genetic testing is an essential part of diagnosis and permits an improved targeting of patients needing follow-up and treatment. In our series, a mutation has been found in most families with LQTS. In all other genetic arrhythmias, the yield of genetic testing is less but nevertheless helpful for medical care of these pts. Conclusion: A multidisciplinary approach to genetic arrhythmias permits a better and more efficient screening and therapy in affected families. It helps families to better understand their disease and improves follow-up in the affected individuals.

Effective Electrodiffusion equation for non uniform nanochannels

We derive a one dimensional formulation of the Planck-Nernst-Poisson equation to describe the dynamics of of a symmetric binary electrolyte in channels whose section is of nanometric section and varies along the axial direction. The approach is in the spirit of the Fick-Jacobs di fusion equation and leads to a system of coupled equations for the partial densities which depends on the charge sitting at the walls in a non trivial fashion. We consider two kinds of non uniformities, those due to the spatial variation of charge distribution and those due to the shape variation of the pore and report one and three-dimensional solutions of the electrokinetic equations.

Mekaanisen puunjalostuksen markkinakartoitus: Koivusahatavaran ja -puolijalosteiden markkinat Euroopassa

Tutkimuksen tavoitteena oli kartoittaa koivusahatavaran ja -puolijalosteiden potentiaalisia vientikohdemaita EU-maissa ja Norjassa. Tarkastelun kohteena olivat koivutuotteiden markkinapotentiaali ja kysyntä sekä puutuotteiden markkinointikanavavaihtoehdot Euroopan puutuotemarkkinoilla. Tutkimuksen teoreettisena lähtökohtana oli tarkastella, kuinka markkinointitutkimuksen avulla kartoitetaan tuotantohyödykemarkkinoita, miten määritetään tuotantohyödykkeen markkinapotentiaali ja kysyntä sekä mitä markkinointikanavavaihtoehtoja puutuotteita valmistavalla yrityksellä on vientimarkkinoille lähdettäessä. Empiirisessä osassa selvitettiin sekä kvantitatiivista että kvalitatiivista tietoa Euroopan puutuotemarkkinoista. Lehtipuu- ja koivusahatavaran vienti-, tuonti- ja tuotantotilastojen pohjalta tarkasteltiin koivun suurimpia vientikohdemaita ja arvioitiin kysyntää tulevaisuudessa. Tämän lisäksi puutuotteiden toimialaorganisaatioiden, asiantuntijoiden, puutuotteita valmistavien yritysten ja maahantuojien haastattelujen avulla muodostettiin kokonaiskuva koivusahatavaran ja -puolijalosteiden markkinapotentiaalista ja koivutuotteiden asemasta Euroopan puutuotemarkkinoilla. Koivu koettiin Euroopan puutuotemarkkinoilla kiinnostavana puulajina ja koivutuotteiden kysyntä onkin ollut viime vuosien aikana nousujohteista. Tämä johtuu suurimmaksi osaksi tällä hetkellä vallitsevasta vaaleiden puulajien trendistä. Markkinoilla menestyminen riippuu kuitenkin siitä, kuinka hyvin koivun tarjoaja pystyy vastaamaan asiakkaiden tuotteelle asettamiin vaatimuksiin.

Hankintastrategian muutoksen vaikutus käyttöpääoman sitoutumiseen: case muodin vähittäiskauppa

Tutkimuksen päätavoitteena on selvittää hankintastrategian muutoksen vaikutusta käyttöpääoman sitoutumiseen. Tutkimus on kvalitatiivinen case-tutkimus. Siinä tutkitaan kohdeyrityksen nuorisomuotimyymälöiden käyttöpääoman kehitystä suhteessa liikevaihtoon viiden vuoden aikasarjalla. Tutkimuksen tiedot ovat kerätty POS-järjestelmästä kuukauden tarkkuudella. Tutkimuksessa seurataan käyttöpääoman trendin lisäksi sesonkivaihteluja. Tutkimusyrityksen uudessa hankintastrategiassa lisättiin sesongin aikaisia express- ja täydennysostojen osuutta. Toimintatavan muutos johti ennakko-ostojen vähenemiseen, mikä puolestaan lyhensi ostojen ja myyntisesongin välistä keskimääräistä aikaa. Lyhyemmät ennakkoajat vähentävät ennustusvirhettä, mikä parantaa varaston hallittavuutta. Parempi ennustettavuus vähentää varmuusvarastojen tarvetta ja joustavampi materiaalivirta tasaa varastonhuippuja. Molemmat tekijät vähentävät myymälöiden käyttöpääoman tarvetta. Tutkimuksen johtopäätöksenä todetaan, että nopeampi toimitusketju vähentää käyttöpääoman tarvetta kohdeyrityksessä. Johtopäätös on yhdenmukainen tutkimuksen teoreettisen viitekehyksen kanssa.