Femoroazetabuläres Impingement als Auslöser der Koxarthrose

Zusammenfassung: Das femoroazetabuläre Impingement (FAI) ist häufig, die geschätzte Prävalenz liegt bei 10-15%. Unsere bisher 10-jährige Erfahrung bestätigt das FAI als eine wesentliche, wenn auch nicht einzige Ursache der Koxarthrose. Isolierte azetabuläre oder femorale Fehlformen sind selten, obwohl bei Frauen die azetabuläre und bei Männern die femorale Pathomorphologie dominiert. Normalbefunde im Standardröntgen schließen ein FAI nicht aus. Symptome treten umso früher auf, je größer die Deformität und je intensiver hohe Bewegungsanforderungen gestellt werden. Die überwiegende Mehrzahl der Patienten ist <40Jahre alt. Im Unterschied zum Impingement bei der Hüftendoprothetik ist das natürliche Gelenk mechanisch viel satter gefasst, was kein Ausweichen im Sinne der Subluxation oder gar Luxation ermöglicht. Entsprechend hoch sind die Impingementkräfte, die beim häufigen, nicht-sphärischen Hüftkopf (femorale Fehlform, Cam-FAI) mit schnellen Bewegungen der Beugung und Innenrotation eine von außen nach innen verlaufende Ablösung des Pfannenknorpels hervorrufen. Der Knorpel des sphärischen Hüftanteils bleibt zunächst intakt, ein Bild, das mit der klassischen Entstehungstheorie der Koxarthrose nicht in Einklang zu bringen ist. Erst wenn der Hüftkopf in die Zone des geschädigten Pfannenknorpels migriert, beeinflussen auch vertikal verlaufende Kräfte den Arthroseverlauf. Risse zwischen Labrum und Knorpel, wie sie im MRT beobachtet werden, sind nicht als Abrisse des Labrum vom Knorpel, sondern Abrisse des Knorpels vom Labrum zu verstehen. Bei der azetabulären Über-Überdachung (azetabuläre Fehlform, Pincer-FAI) ist das Labrum die erste Struktur, die geschädigt wird, der Knorpelschaden tritt sekundär auf. Die Behandlung des FAI bei Patienten <40Jahren erfolgt, wenn möglich, gelenkerhaltend. Ist die Knorpelschädigung ausgedehnt, ist bei gleichem Aufwand ein schlechteres Ergebnis der chirurgischen Therapie zu erwarten als bei geringem Schaden. Entsprechend wichtig ist die frühe Diagnosestellung, mit der neben der Einleitung der kausalen Therapie auch die beruflichen und sportlichen Weichen angepasst werden solle

Childhood maltreatment, psychological resources, and depressive symptoms in women with breast cancer.

Childhood maltreatment is associated with elevated risk for depression across the human lifespan. Identifying the pathways through which childhood maltreatment relates to depressive symptoms may elucidate intervention targets that have the potential to reduce the lifelong negative health sequelae of maltreatment exposure. In this cross-sectional study, 271 women with early-stage breast cancer were assessed after their diagnosis but before the start of adjuvant treatment (chemotherapy, radiation, endocrine therapy). Participants completed measures of childhood maltreatment exposure, psychological resources (optimism, mastery, self-esteem, mindfulness), and depressive symptoms. Using multiple mediation analyses, we examined which psychological resources uniquely mediated the relationship between childhood maltreatment and depressive symptoms. Exposure to maltreatment during childhood was robustly associated with lower psychological resources and elevated depressive symptoms. Further, lower optimism and mindfulness mediated the association between childhood maltreatment and elevated depressive symptoms. These results support existing theory that childhood maltreatment is associated with lower psychological resources, which partially explains elevated depressive symptoms in a sample of women facing breast cancer diagnosis and treatment. These findings warrant replication in populations facing other major life events and highlight the need for additional studies examining childhood maltreatment as a moderator of treatment outcomes

New Results from NA49

We present recent results of the SPS experiment NA49 on production of strange particles and event-by-event fluctuations of mean $p_t$ and of charged particle ratios in central Pb+Pb collisions at various beam energies (40, 80, 158 AGeV) as well as in different collisions at 158 AGeV, going from p+p over light-ion collisions to peripheral and central Pb+Pb.Comment: 5 pages, 6 figures (in eps) talk given at XXXI International Symposium on Multiparticle Dynamics, Sep. 1-7, 2001, Datong China URL http://ismd31.ccnu.edu.cn

Microscopic mechanisms of thermal and driven diffusion of non rigid molecules on surfaces

The motion of molecules on solid surfaces is of interest for technological applications such as catalysis and lubrication, but it is also a theoretical challenge at a more fundamental level. The concept of activation barriers is very convenient for the interpretation of experiments and as input for Monte Carlo simulations but may become inadequate when mismatch with the substrate and molecular vibrations are considered. We study the simplest objects diffusing on a substrate at finite temperature $T$, namely an adatom and a diatomic molecule (dimer), using the Langevin approach. In the driven case, we analyse the characteristic curves, comparing the motion for different values of the intramolecular spacing, both for T=0 and $T\ne 0$. The mobility of the dimer is higher than that of the monomer when the drift velocity is less than the natural stretching frequency. The role of intramolecular excitations is crucial in this respect. In the undriven case, the diffusive dynamics is considered as a function of temperature. Contrary to atomic diffusion, for the dimer it is not possible to define a single, temperature independent, activation barrier. Our results suggest that vibrations can account for drastic variations of the activation barrier. This reveals a complex behaviour determined by the interplay between vibrations and a temperature dependent intramolecular equilibrium length.Comment: 6 pages, 5 figures, Proceeding of the EMRS 2002 Conference, to be published in Thin Solid Film

Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib.

BackgroundEarly detection of adverse effects of novel therapies and understanding of their mechanisms could improve the safety and efficiency of drug development. We have retrospectively applied large-scale proteomics to blood samples from ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), a trial of torcetrapib (a cholesterol ester transfer protein inhibitor), that involved 15 067 participants at high cardiovascular risk. ILLUMINATE was terminated at a median of 550 days because of significant absolute increases of 1.2% in cardiovascular events and 0.4% in mortality with torcetrapib. The aims of our analysis were to determine whether a proteomic analysis might reveal biological mechanisms responsible for these harmful effects and whether harmful effects of torcetrapib could have been detected early in the ILLUMINATE trial with proteomics.MethodsA nested case-control analysis of paired plasma samples at baseline and at 3 months was performed in 249 participants assigned to torcetrapib plus atorvastatin and 223 participants assigned to atorvastatin only. Within each treatment arm, cases with events were matched to controls 1:1. Main outcomes were a survey of 1129 proteins for discovery of biological pathways altered by torcetrapib and a 9-protein risk score validated to predict myocardial infarction, stroke, heart failure, or death.ResultsPlasma concentrations of 200 proteins changed significantly with torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in endocrine systems, including in aldosterone function and glycemic control. At baseline, 9-protein risk scores were similar in the 2 treatment arms and higher in participants with subsequent events. At 3 months, the absolute 9-protein derived risk increased in the torcetrapib plus atorvastatin arm compared with the atorvastatin-only arm by 1.08% (P=0.0004). Thirty-seven proteins changed in the direction of increased risk of 49 proteins previously associated with cardiovascular and mortality risk.ConclusionsHeretofore unknown effects of torcetrapib were revealed in immune and inflammatory functions. A protein-based risk score predicted harm from torcetrapib within just 3 months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00134264

Graviton to Photon Conversion via Parametric Resonance

We study the parametric resonance excitation of the electromagnetic field by a gravitational wave. We show that there is narrow band resonance. For an electromagnetic field in the vacuum the resonance occurs only in the second band, and its strength is thus suppressed by two powers of amplitude of the gravitational wave. On the other hand, in the case of an electromagnetic field in a medium with the speed of light smaller than 1 (in natural units), there is a band of Fourier modes which undergo resonance in the first band.Comment: 7 pages, 2 figures; v2 remarks added; v3 version accepted by Physics of the Dark Univers

The Strong Maximum Circulation Algorithm: A New Method for Aggregating Preference Rankings

We present a new optimization-based method for aggregating preferences in settings where each decision maker, or voter, expresses preferences over pairs of alternatives. The challenge is to come up with a ranking that agrees as much as possible with the votes cast in cases when some of the votes conflict. Only a collection of votes that contains no cycles is non-conflicting and can induce a partial order over alternatives. Our approach is motivated by the observation that a collection of votes that form a cycle can be treated as ties. The method is then to remove unions of cycles of votes, or circulations, from the vote graph and determine aggregate preferences from the remainder. We introduce the strong maximum circulation which is formed by a union of cycles, the removal of which guarantees a unique outcome in terms of the induced partial order. Furthermore, it contains all the aggregate preferences remaining following the elimination of any maximum circulation. In contrast, the well-known, optimization-based, Kemeny method has non-unique output and can return multiple, conflicting rankings for the same input. In addition, Kemeny's method requires solving an NP-hard problem, whereas our algorithm is efficient, based on network flow techniques, and runs in strongly polynomial time, independent of the number of votes. We address the construction of a ranking from the partial order and show that rankings based on a convex relaxation of Kemeny's model are consistent with our partial order. We then study the properties of removing a maximal circulation versus a maximum circulation and establish that, while maximal circulations will in general identify a larger number of aggregate preferences, the partial orders induced by the removal of different maximal circulations are not unique and may be conflicting. Moreover, finding a minimum maximal circulation is an NP-hard problem.Comment: 22 pages, 4 figure

Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload

Iron overload is the hallmark of hereditary hemochromatosis and a complication of iron-loading anemias such as β-thalassemia. Treatment can be burdensome and have significant side effects, and new therapeutic options are needed. Iron overload in hereditary hemochromatosis and β-thalassemia intermedia is caused by hepcidin deficiency. Although transgenic hepcidin replacement in mouse models of these diseases prevents iron overload or decreases its potential toxicity, natural hepcidin is prohibitively expensive for human application and has unfavorable pharmacologic properties. Here, we report the rational design of hepcidin agonists based on the mutagenesis of hepcidin and the hepcidin-binding region of ferroportin and computer modeling of their docking. We identified specific hydrophobic/aromatic residues required for hepcidin-ferroportin binding and obtained evidence in vitro that a thiol-disulfide interaction between ferroportin C326 and the hepcidin disulfide cage may stabilize binding. Guided by this model, we showed that 7–9 N-terminal amino acids of hepcidin, including a single thiol cysteine, comprised the minimal structure that retained hepcidin activity, as shown by the induction of ferroportin degradation in reporter cells. Further modifications to increase resistance to proteolysis and oral bioavailability yielded minihepcidins that, after parenteral or oral administration to mice, lowered serum iron levels comparably to those after parenteral native hepcidin. Moreover, liver iron concentrations were lower in mice chronically treated with minihepcidins than those in mice treated with solvent alone. Minihepcidins may be useful for the treatment of iron overload disorders

Conservadorismo contábil em empresas complexas

O estudo busca averiguar a influência da complexidade de empresas nos níveis de conservadorismo contábil. O tema de análise, conservadorismo contábil em empresas complexas, pode ser considerado relevante porque analisa as práticas de conservadorismo levando em conta o contexto organizacional das empresas, fato ignorado em outros estudos que investigam os incentivos ou determinantes do conservadorismo contábil, pelo menos quanto à complexidade empresarial. A pesquisa apresenta evidências estatísticas de que o conservadorismo contábil varia de forma positiva com a assimetria da informação ocasionada por características específicas de ambientes complexos. Em contrapartida, quando estas apresentam, em conjunto, diversas características complexas, então a tendência é de pouca adoção do conservadorismo. Além disso, a presente pesquisa reúne evidências que visam a contribuir para a ciência contábil pela análise de empresas complexas e conservadorismo, e não práticas oportunistas observadas em estudos prévios. A amostra refere-se a 110 empresas de capital aberto no período de 2010 a 2016. A coleta de dados foi realizada por meio de relatórios das empresas, como formulários de referência, dados cadastrais e notas explicativas, bem como da base de dados Economatica®. A análise dos dados foi realizada por meio de regressão linear múltipla e regressão quantílica. Evidências obtidas na pesquisa indicam que o conservadorismo contábil varia conforme a assimetria de informação ocasionada por ambientes complexos em que pode apresentar uma relação positiva em empresas com poucas características de complexidade ou relação negativa se a empresa tem complexidade em diversas características ao mesmo tempo. Lança luz, então, sobre os diferentes níveis de conservadorismo observados nas empresas que muitas vezes podem ser atribuídos a mecanismos de governança, cultura organizacional, padrões contábeis, entre outros fatores, resultados que podem estar enviesados por não considerar o fator complexidade de empresas.This study seeks to investigate the influence of the complexity of companies on levels of accounting conservatism. The subject of analysis, accounting conservatism in complex companies, can be considered relevant because it analyzes conservative practices taking into account the organizational context of companies; something that is ignored in other studies that investigate the incentives or determinants of accounting conservatism, at least as far as firm complexity is concerned. The research presents statistical evidence that accounting conservatism varies positively with the information asymmetry caused by specific characteristics of complex environments. On the other hand, when companies present several complex characteristics together, then the trend is one of little adoption of conservatism. In addition, this research brings together evidence that aims to contribute to accounting science by analyzing complex companies and conservatism and not the opportunistic practices observed in previous studies. The sample refers to 110 publicly traded companies from 2010 to 2016. The data collection was carried out using company reports, such as reference forms, registration data, and explanatory notes, as well as the Economatica® database. The data analysis was performed using multiple linear regression and quantile regression. The evidence obtained in the research indicates that accounting conservatism varies according to the information asymmetry caused by complex environments, in which it can present a positive relationship in companies with few characteristics of complexity, or a negative relationship if the company has complexity in several characteristics at the same time. It throws light on the different levels of conservatism observed in companies, which can often be attributed to mechanisms of governance, organizational culture, and accounting standards, among other factors, which are results that may be biased if the company complexity factor is not considered

Generative discriminative models for multivariate inference and statistical mapping in medical imaging

This paper presents a general framework for obtaining interpretable multivariate discriminative models that allow efficient statistical inference for neuroimage analysis. The framework, termed generative discriminative machine (GDM), augments discriminative models with a generative regularization term. We demonstrate that the proposed formulation can be optimized in closed form and in dual space, allowing efficient computation for high dimensional neuroimaging datasets. Furthermore, we provide an analytic estimation of the null distribution of the model parameters, which enables efficient statistical inference and p-value computation without the need for permutation testing. We compared the proposed method with both purely generative and discriminative learning methods in two large structural magnetic resonance imaging (sMRI) datasets of Alzheimer's disease (AD) (n=415) and Schizophrenia (n=853). Using the AD dataset, we demonstrated the ability of GDM to robustly handle confounding variations. Using Schizophrenia dataset, we demonstrated the ability of GDM to handle multi-site studies. Taken together, the results underline the potential of the proposed approach for neuroimaging analyses.Comment: To appear in MICCAI 2018 proceeding