Etude expérimentale à l'aide de couches minces de l'influence de l'oxydation sur l'adhésion entre un insert et une coulée en aluminium

Motor parts produced by casting are subjected to particularly high local stresses and must be reinforced by high-strength inserts. The insertion is normally made mechanically after casting, but, if good adhesion could be obtained, it would be preferable to place the inserts into the cast prior to production. The inert, insulating oxide layer which forms spontaneously on aluminium surfaces tends to prevent the insert and cast metals from interdiffusing, thereby rendering adhesion difficult. To solve the adhesion problem several different aspects of the casting process must be investigated. One important aspect concerns surface treatment, where it has been shown that deposition, onto the surface of the insert prior to casting, of a silver-zinc-silver multi-layer structure improves adhesion. The objective of the present work is to study the role that aluminium and zinc oxidation plays in adhesion between the insert and the casted part. The multi-layer structure is investigated by studying independently several single-layer systems, obtained by magnetron sputtering. The substrates are oxidized prior to deposition by anodic polarization or thermal treatment. The adhesion of the deposits is characterized by scratch tests, consisting of linear displacement with increasing normal load of an indenter along the surface of the samples. Normal and tangential forces are measured. Under certain conditions, adhesion can be associated with the applied normal force corresponding to the appearance of defects in the scratch. It can be shown that certain measured force transitions can be correlated with these defects and used to improve resolution and simplify interpretation of the measurements. The results obtained show that for zinc as well as for aluminium an increase in oxide-layer thickness results in a decrease in deposit adhesion. The relative decrease in adhesion as a function of the thickness of the oxide layer is the same for all of the systems studied. Nevertheless, thermal oxidation of the zinc is much faster than that of aluminium, and the zinc layers must be further coated with silver prior to casting

Inferential misconceptions and replication crisis

Misinterpretations of the p value and the introduction of bias through arbitrary analytical choices have been discussed in the literature for decades. Nonetheless, they seem to have persisted in empirical research, and criticisms of p value misuses have increased in the recent past due to the non-replicability of many studies. Unfortunately, the critical concerns that have been raised in the literature are scattered over many disciplines, often linguistically confusing, and differing in their main reasons for criticisms. Misuses and misinterpretations of the p value are currently being discussed intensely under the label “replication crisis” in many academic disciplines and journals, ranging from specialized scientific journals to Nature and Science. In a drastic response to the crisis, the editors of the journal Basic and Applied Social Psychology even decided to ban the use of p values from future publications at the beginning of 2015, a fact that has certainly added fuel to the discussions in the relevant scientific forums. Finally, in early March, the American Statistical Association released a brief formal statement on p values that explicitly addresses misuses and misinterpretations. In this context, we systematize the most serious flaws related to the p value and discuss suggestions of how to prevent them and reduce the rate of false discoveries in the future

A practical approach to the guideline-directed pharmacological treatment of heart failure with reduced ejection fraction

Over the last 15–20 years, remarkable developments of heart failure (HF) pharmacotherapies have been achieved. However, HF remains a global healthcare challenge with more than 64 million patients worldwide. Optimization of guideline-directed chronic HF medical therapy is highly recommended with every patient visit to improve outcomes in patients with HF with reduced ejection fraction. However, the majority of patients in real-world settings are treated with doses that are lower than those with proven efficacy in clinical trials, which might be due to concerns of adverse effects and inertia of physicians. Likewise, a significant proportion of patients still do not receive all drug classes that could improve their prognosis. The recent European Society of Cardiology guidelines do not provide detailed recommendations on how these drug classes should be implemented in the treatment of inpatients to allow for both safety and a high likelihood of efficacy. We therefore propose a practical approach algorithm to support physicians to treat HF patients in their daily practice

Intestinal Tritrichomonas foetus infection in cats in Switzerland detected by in vitro cultivation and PCR

Tritrichomonas foetus, a parasite well known for its significance as venereally transmitted pathogen in cattle, has recently been identified as a cause of chronic large-bowel diarrhea in domestic cats in the US, UK, and, more recently, also in Norway. In a period of 3months (October to December 2007), 45 cats of Switzerland suffering from chronic diarrhea were investigated for intestinal infections, including a search for trichomonads. A commercially available in vitro culture system was used to screen for infection, complemented with a PCR and subsequent amplicon sequencing to support speciation. The PCR is based upon amplification of a sequence derived from the internal transcribed spacer region 1 (ITS1) on the ribosomal RNA gene (rRNA) using primers designed to detect a broad range of genera and species belonging to the family of Trichomonadidae. The method was furthermore adapted to the uracil DNA glycosylase (UDG) system in order to prevent carry-over contamination and it included a recombinant internal control to track for inhibitory reactions. Eleven out of the 45 cats were culture-positive, as revealed by microscopic identification of trichomonadid organisms. One of the isolates was subjected to scanning electron microscopy and findings revealed the presence of three flagella, thus placing the isolate into the gender Tritrichomonas sp. PCR and subsequent amplicon sequencing were carried out with ten of the 11 isolates. A total homology with published T. foetus sequences was confirmed in all of the cases. T. foetus therefore appears to range among those organisms that can cause chronic diarrhea in cats in Switzerlan

Induction of Krüppel-Like Factor 4 Mediates Polymorphonuclear Neutrophil Activation in Streptococcus pneumoniae Infection

The recruitment and activation of polymorphonuclear neutrophils (PMNs) are of central importance for the elimination of pathogens in bacterial infections. We investigated the Streptococcus pneumoniae-dependent induction of the transcription factor Kruppel-like factor (KLF) 4 in PMNs as a potential regulator of PMN activation. We found that KLF4 expression is induced in human blood-derived PMNs in a time- and dose-dependent manner by wild-type S. pneumoniae and capsule knockout mutants. Unencapsulated knockout mutants induced stronger KLF4 expression than encapsulated wild types. The presence of autolysin LytA-competent (thus viable) pneumococci and LytA-mediated bacterial autolysis were required for KLF4 induction in human and murine PMNs. LyzMcre-mediated knockdown of KLF4 in murine blood-derived PMNs revealed that KLF4 influences pneumococci killing and increases the release of the proinflammatory cytokines tumor necrosis factor alpha and keratinocyte chemoattractant and decreases the release of the anti-inflammatory cytokine interleukin-10. Thus, S. pneumoniae induces KLF4 expression in PMNs, which contributes to PMN activation in S. pneumoniae infection

What is the role of Swiss domestic cats in environmental contamination with Echinococcus multilocularis eggs?

Background The role of the domestic cat as definitive host for Echinococcus multilocularis and thus in environmental contamination with eggs has not yet been entirely resolved. This study aimed to assess the prevalence of E. multilocularis and other gastrointestinal parasites in Swiss domestic cats and to compare the diagnostic sensitivity of different methods for the detection of intestinal taeniid infection. Methods Faecal samples from 146 cats were included in the study. Faecal samples only were available from 55 cats; for the other 91 cats, necropsy was performed in addition to faecal sample testing. All (n = 146) faecal samples were analysed by a combined sedimentation/flotation technique (44% ZnCl2) and by the sodium acetate-acetic acid-formalin (SAF) sedimentation technique; when sufficient material was available (n = 121 samples) the Baermann-Wetzel technique was also used. Additionally, all samples were analysed by two coproantigen (copro)-quantitative PCRs (qPCR): (i) a multiplex qPCR able to detect and differentiate between E. multilocularis, Echinococcus granulosus sensu lato and Taenia spp./other cestodes (CEST-qPCR) and (ii) an E. multilocularis-specific qPCR (EM-qPCR). Finally, the intestines were examined macroscopically and microscopically for parasite stages at necropsy (n = 91) and using an intestinal scraping technique (IST) (n = 64). Results Of the 146 cats examined, 24 (17.1%) were infected by intestinal parasites, namely Hydatigera (syn. Taenia) taeniaeformis (8.9%), Toxocara cati (6.1%), Capillaria sp. (3.4%), hookworms (3.4%), Mesocestoides litteratus (1.4%), Giardia sp. (1.4%), Cystoisospora rivolta (1.4%), Cystoisospora felis (0.7%), Toxoplasma gondii (0.7%), Hammondia hammondi (0.7%) and Strongyloides sp. (0.7%). Necropsy and the IST revealed adult H. taeniaeformis in 12 animals, of which eight faecal samples were positive by the CEST-qPCR (sensitivity = 67%) and six samples by the sedimentation/flotation technique (sensitivity = 50%). No E. multilocularis infection was detected in the sampled cats. Using Bayesian latent class analysis, the mean posterior prevalence probability was 0.0% (95% confidence interval 0–0.83%) for E. multilocularis. Conclusions There was no evidence of E. multilocularis infection among the 146 cats examined, suggesting that the prevalence of this parasite is low (< 1%) in the Swiss domestic cat population. Nonetheless, some of the sampled cats were infected by parasites that have rodents as intermediate hosts, demonstrating successful predation by these cats, and some were infected with zoonotic parasites. Cats therefore should not be disregarded as potential hosts for E. multilocularis and other zoonotic parasites

Striatins as plaque molecules of zonulae adhaerentes in simple epithelia, of tessellate junctions in stratified epithelia, of cardiac composite junctions and of various size classes of lateral adherens junctions in cultures of epithelia- and carcinoma-derived cells

Proteins of the striatin family (striatins 1–4; sizes ranging from 90 to 110 kDa on SDS-polyacrylamide gel electrophoresis) are highly homologous in their amino acid sequences but can differ in their cell-type-specific gene expression patterns and biological functions. In various cell types, we have found one, two or three polypeptides of this evolutionarily old and nearly ubiquitous family of proteins known to serve as scaffold proteins for diverse protein complexes. Light and electron microscopic immunolocalization methods have revealed striatins in mammalian cell-cell adherens junctions (AJs). In simple epithelia, we have localized striatins as constitutive components of the plaques of the subapical zonulae adhaerentes of cells, including intestinal, glandular, ductal and urothelial cells and hepatocytes. Striatins colocalize with E-cadherin or E–N-cadherin heterodimers and with the plaque proteins α- and β-catenin, p120 and p0071. In some epithelia and carcinomas and in cultured cells derived therefrom, striatins are also seen in lateral AJs. In stratified epithelia and in corresponding squamous cell carcinomas, striatins can be found in plaques of some forms of tessellate junctions. Moreover, striatins are major plaque proteins of composite junctions (CJs; areae compositae) in the intercalated disks connecting cardiomyocytes, colocalizing with other CJ molecules, including plectin and ankyrin-G. We discuss the “multimodulator” scaffold roles of striatins in the initiation and regulation of the formation of various complex particles and structures. We propose that striatins are included in the diagnostic candidate list of proteins that, in the CJs of human hearts, can occur in mutated forms in the pathogeneses of hereditary cardiomyopathies, as seen in some types of genetically determined heart damage in boxer dogs.German-Israeli Foundation for Scientific Research and Development (GIF grant I-1098-43.11/2010

Quantitative PCR for the diagnosis of cutaneous leishmaniasis from formalin-fixed and paraffin-embedded skin sections.

The present report describes a real-time PCR-based procedure to reliably determine the quantity of Leishmania amastigotes in relation to the amount of host tissue in histological skin sections from canine and equine cases of cutaneous leishmaniasis. The novel diagnostic Leishmania-PCR has a detection limit of <0.02 amastigotes per μg tissue, which corresponds well to the detection limit of immunohistochemistry and is far beyond that of conventional histology. Our results emphasise the importance of PCR to complement routine histology of cutaneous leishmaniasis cases, particularly in laboratories in which no immunohistochemical assay is available

Impact of percutaneous mitral valve repair using the MitraClip™ system on ventricular arrhythmias and ICD therapies

Transcatheter edge-to-edge repair (TEER) using the MitraClip™ device has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high or prohibitive surgical risk. Only limited information regarding the impact of TEER on ventricular arrhythmias (VA) has been reported. The aim of the present study was to assess the impact of TEER using the MitraClip(TM) device on the burden of VA and ICD (Implantable Cardioverter Defibrillator) therapies. Among 600 MitraClip(TM) implantations performed in our clinic between September 2009 and October 2018, we identified 86 patients with successful TEER and an active implantable cardiac device (pacemaker, ICD, CRT-P/D (Cardiac Resynchronization Therapy-Pacemaker/Defibrillator)) eligible for retrospective VA analyses. These patients presented with mainly functional MR (81.4%) and severely reduced left ventricular ejection fraction (mean LVEF 22.1% ± 10.3%). The observation period comprised 456 ± 313 days before and 424 ± 287 days after TEER. The burden of ventricular arrhythmias (sustained ventricular tachycardia (sVT) and ventricular fibrillation (VF)) was significantly reduced after TEER (0.85 ± 3.47 vs. 0.43 ± 2.03 events per patient per month, p = 0.01). Furthermore, the rate of ICD therapies (anti-tachycardia pacing (ATP) and ICD shock) decreased significantly after MitraClip(TM) implantation (1.0 ± 3.87 vs. 0.32 ± 1.41, p = 0.014). However, reduction of VA burden did not result in improved two-year survival in this patient cohort with severely reduced LVEF. Mitral valve TEER using the MitraClip™ device was associated with a significant reduction of ventricular arrhythmias and ICD therapies

Functional improvement following direct interventional leaflet repair of severe tricuspid regurgitation

AIMS: Several new percutaneous tricuspid repair systems have recently been introduced as new treatment options for severe tricuspid regurgitation (TR). Clinical improvement following percutaneous tricuspid valve leaflet repair has been demonstrated by recent studies. A possible impact on exercise capacity has not yet been reported. METHODS AND RESULTS: Eleven patients with at least severe TR and successful tricuspid leaflet repair using the PASCAL Ace implant at our cardiology department were included in this analysis. All patients suffered from symptomatic right‐sided heart failure with compromised exercise capacity. Cardiopulmonary exercise testing (CPET), clinical, laboratory, and echocardiographic parameters were assessed at baseline and 3 months follow‐up. The primary endpoint was the change in maximal oxygen consumption [VO(2) max (mL/(min*kg))] at 3 months follow‐up. Secondary endpoints included improvement in TR, cardiac biomarkers, and other clinical outcomes. TR severity at 3 months follow‐up post‐PASCAL Ace implantation was significantly lower than at baseline (P = 0.004). Cardiac biomarkers including high‐sensitivity troponin T and N‐terminal pro‐brain natriuretic peptide as well as right ventricular diameter improved slightly without reaching statistical significance (P = 0.89, P = 0.32, and P = 0.06, respectively). PASCAL Ace implantation resulted in a significant improvement in cardiopulmonary exercise capacity at 3 months follow‐up compared with baseline. Mean VO(2) max improved from 9.5 ± 2.8 to 11.4 ± 3.4 mL/(min*kg) (P = 0.006), VO(2) max per cent predicted from 42 ± 12% to 50 ± 15% (P = 0.004), peak oxygen uptake from 703 ± 175 to 826 ± 198 mL/min (P = 0.004), and O(2) pulse per cent predicted from 67 ± 21% to 81 ± 25% (P = 0.011). Other CPET‐related outcomes did not show any significant change over time. CONCLUSIONS: In this single‐centre retrospective analysis, direct tricuspid valve leaflet repair using the transcatheter PASCAL Ace implant system was associated with a reduced TR severity and improved cardiopulmonary exercise capacity