Low frequency 1/f noise in doped manganite grain-boundary junctions

We have performed a systematic analysis of the low frequency 1/f-noise in single grain boundary junctions in the colossal magnetoresistance material La_{2/3}Ca_{1/3}MnO_{3-delta}. The grain boundary junctions were formed in epitaxial La_{2/3}Ca_{1/3}MnO_{3-delta} films deposited on SrTiO_3 bicrystal substrates and show a large tunneling magnetoresistance of up to 300% at 4.2 K as well as ideal, rectangular shaped resistance versus applied magnetic field curves. Below the Curie temperature T_C the measured 1/f noise is dominated by the grain boundary. The dependence of the noise on bias current, temperature and applied magnetic field gives clear evidence that the large amount of low frequency noise is caused by localized sites with fluctuating magnetic moments in a heavily disordered grain boundary region. At 4.2 K additional temporally unstable Lorentzian components show up in the noise spectra that are most likely caused by fluctuating clusters of interacting magnetic moments. Noise due to fluctuating domains in the junction electrodes is found to play no significant role.Comment: 9 pages, 7 figure

Approche psychophysique de la perception auditive para et extra linguistique chez le sujet sourd post lingual implanté cochléaire

Les bénéfices liés à l'implantation cochléaire sont connus pour la discrimination de la parole dans le silence. En revanche, leurs capacités perceptives pour les informations para linguistiques et extra linguistiques sont moins décrites. Nos travaux expérimentaux ont consisté à caractériser les éventuels déficits observés et expliquer leurs mécanismes pour la catégorisation auditive, pour la perception de la prosodie et de la musique. Nous avons dans ce but réalisé plusieurs études psychophysiques dans lesquelles leurs performances étaient comparées à celles de sujets contrôle normo entendant. Nos résultats font état d'un important déficit de perception auditive para et extra linguistique chez les sujets implantés cochléaires, vraisemblablement lié à deux principales raisons. La première réside dans la dégradation spectrale du signal acoustique par le processeur vocal de l'implant et l'insuffisance de restitution de l'information relative à la fréquence fondamentale. C'est pourquoi le déficit apparaît réduit voire absent chez les sujets bénéficiant d'une audition résiduelle associée à l'implant. La deuxième raison tient à la réorganisation corticale suivant la période de surdité, qui facilite le traitement de la parole mais pourrait se révéler délétère pour la perception des autres informations auditives.Cochlear implants have been shown to restore excellent speech recognition in quiet. However, post lingually deafened adults experience persistent handicap following cochlear implantation, which might be related to their perception abilities in other auditory fields than speech. In this report, we conducted several psychophysical experiments, which aimed at assessing the characteristics of their auditory categorization and their abilities for prosody and music perception. Normal hearing subjects were also tested in a control group. We found a strong and durable deficit, underpinned by two plausible mechanisms. First, the acoustic signal processing through the implant leads to an important spectral impoverishment and limits access to fundamental frequency information. Hence some cochlear implant recipients with substantial low-frequency residual hearing may achieve near normal performance. Brain plasticity following auditory deprivation facilitates the compensatory strategies for speech recognition but might also influence negatively the outcomes in para linguistic and extra linguistic information

Guideline recommendations and the positioning of newer drugs in type 2 diabetes care

Cardiovascular outcome trials in patients with type 2 diabetes at high cardiovascular risk have led to remarkable advances in our understanding of the effectiveness of GLP-1 receptor agonists and SGLT2 inhibitors to reduce cardiorenal events. In 2019, the American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and European Society of Cardiology (ESC) published updated recommendations for the management of such patients. We are concerned that ongoing discussions focusing on the differences between the endocrinologists' consensus report from the ADA and EASD and cardiologists' guidelines from the ESC are contributing to clinical inertia, thereby effectively denying evidence-based treatments advocated by both groups to patients with type 2 diabetes and cardiorenal disease. A subset of members from the writing groups of the ADA–EASD consensus report and the ESC guidelines was convened to emphasise where commonalities exist and to propose an integrated framework that encompasses the views incorporated in management approaches proposed by the ESC and the ADA and EASD. Coordinated action is required to ensure that people with type 2 diabetes, cardiovascular disease, heart failure, or chronic kidney disease are treated appropriately with an SGLT2 inhibitor or GLP-1 receptor agonist. In our opinion, this course should be initiated independent of background therapy, current glycaemic control, or individualised treatment goals

Amplification of the poorer ear by StereoBiCROS in case of asymmetric sensorineural hearing loss: effect on tinnitus

Tinnitus is prevalent among patients suffering from Single-Sided Deafness (SSD) and Asymmetrical Hearing Loss (AHL). In addition to bothersome tinnitus in the poorer ear, these patients also report issues with understanding speech in noise and sound localization. The conventional treatment options offered to these patients to improve auditory abilities are cochlear implantation, bone conduction devices or Contralateral Routing Of Signal (CROS) hearing aids. It was recently found that the benefit of cochlear implantation for tinnitus associated with AHL/SSD was greater than the other two approaches. It is conceivable that the lack of stimulation provided to the poorer ear in these last approaches explains their modest impact on tinnitus perception. A new technology that combines the ability to reroute the sound from the poorer ear to the good ear (CROS system) while still stimulating the poorer ear with conventional sound amplification has recently been developed: the StereoBiCROS system. The aim of this study was to investigate the effects of this new device on tinnitus. Twelve AHL and two SSD patients aged 70.7 ± 7.9 years with tinnitus were fitted with bilateral hearing aids that included 3 programs: Stereophonic, BiCROS and StereoBiCROS (CROS + bilateral amplification). The short-and long-term effect of the approach on tinnitus was assessed using a tinnitus Loudness Visual Analog Scale (VAS) and the Tinnitus Handicap Inventory (THI), respectively. Both the VAS and the THI were used before and one month after the hearing aid fitting. Of the 14 patients who used their hearing aids daily (12.6 ± 1.6 h per day) the StereoBiCROS program was the most used program (81.8 ± 20.5% of the time). The average THI total score decreased from 47 (± 22) to 15 (± 16) (p = 0.002) and the VAS-Loudness score decreased from 7 (± 1) to 2 (± 2) (p < 0.001) after the one-month trial period. In conclusion, StereoBiCROS stimulation strategy seems to offer an effective alternative to reduce tinnitus handicap and loudness for patients with AHL/SSD and tinnitus. This effect may be driven by sound amplification of the poorer ear

Development and evaluation of the modiolar research array – multi-centre collaborative study in human temporal bones

OBJECTIVE: Multi-centre collaborative study to develop and refine the design of a prototype thin perimodiolar cochlear implant electrode array and to assess feasibility for use in human subjects. STUDY DESIGN: Multi-centre temporal bone insertion studies. MATERIALS AND METHODS: The modiolar research array (MRA) is a thin pre-curved electrode that is held straight for initial insertion with an external sheath rather than an internal stylet. Between November 2006 and February 2009, six iterations of electrode design were studied in 21 separate insertion studies in which 140 electrode insertions were performed in 85 human temporal bones by 12 surgeons. These studies aimed at addressing four fundamental questions related to the electrode concept, being: (1) Could a sheath result in additional intra-cochlear trauma? (2) Could a sheath accommodate variations in cochlea size and anatomies? (3) Could a sheath be inserted via the round window? and (4) Could a sheath be safely removed once the electrode had been inserted? These questions were investigated within these studies using a number of evaluation techniques, including X-ray and microfluoroscopy, acrylic fixation and temporal bone histologic sectioning, temporal bone microdissection of cochlear structures with electrode visualization, rotational tomography, and insertion force analysis. RESULTS: Frequent examples of electrode rotation and tip fold-over were demonstrated with the initial designs. This was typically caused by excessive curvature of the electrode tip, and also difficulty in handling of the electrode and sheath. The degree of tip curvature was progressively relaxed in subsequent versions with a corresponding reduction in the frequency of tip fold-over. Modifications to the sheath facilitated electrode insertion and sheath removal. Insertion studies with the final MRA design demonstrated minimal trauma, excellent perimodiolar placement, and very small electrode dimensions within scala tympani. Force measurements in temporal bones demonstrated negligible force on cochlear structures with angular insertion depths of between 390 and 450°. CONCLUSION: The MRA is a novel, very thin perimodiolar prototype electrode array that has been developed using a systematic collaborative approach. The different evaluation techniques employed by the investigators contributed to the early identification of issues and generation of solutions. Regarding the four fundamental questions related to the electrode concept, the studies demonstrated that (1) the sheath did not result in additional intra-cochlear trauma; (2) the sheath could accommodate variations in cochlea size and anatomies; (3) the sheath was more successfully inserted via a cochleostomy than via the round window; and (4) the sheath could be safely removed once the electrode had been inserted

Clinical investigation of the Nucleus Slim Modiolar Electrode

Aims: The Nucleus CI532 cochlear implant incorporates a new precurved electrode array, i.e., the Slim Modiolar electrode (SME), which is designed to bring electrode contacts close to the medial wall of the cochlea while avoiding trauma due to scalar dislocation or contact with the lateral wall during insertion. The primary aim of this prospective study was to determine the final position of the electrode array in clinical cases as evaluated using flat-panel volume computed tomography. Methods: Forty-five adult candidates for unilateral cochlear implantation were recruited from 8 centers. Eleven surgeons attended a temporal bone workshop and received further training with a transparent plastic cochlear model just prior to the first surgery. Feedback on the surgical approach and use of the SME was collected via a questionnaire for each case. Computed tomography of the temporal bone was performed postoperatively using flat-panel digital volume tomography or cone beam systems. The primary measure was the final scalar position of the SME (completely in scala tympani or not). Secondly, medial-lateral position and insertion depth were evaluated. Results: Forty-four subjects received a CI532. The SME was located completely in scala tympani for all subjects. Pure round window (44% of the cases), extended round window (22%), and inferior and/or anterior cochleostomy (34%) approaches were successful across surgeons and cases. The SME was generally positioned close to the modiolus. Overinsertion of the array past the first marker tended to push the basal contacts towards the lateral wall and served only to increase the insertion depth of the first electrode contact without increasing the insertion depth of the most apical electrode. Complications were limited to tip fold-overs encountered in 2 subjects; both were attributed to surgical error, with both reimplanted successfully. Conclusions: The new Nucleus CI532 cochlear implant with SME achieved the design goal of producing little or no trauma as indicated by consistent scala tympani placement. Surgeons should be carefully trained to use the new deployment method such that tip fold-overs and over insertion may be avoided

CVOT summit report 2024: new cardiovascular, kidney, and metabolic outcomes

The 10th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on December 5–6, 2024. This year, discussions about cardiovascular (CV) and kidney outcome trials centered on the recent findings from studies involving empagliflozin (EMPACT-MI), semaglutide (STEP-HFpEF-DM and FLOW), tirzepatide (SURMOUNT-OSA and SUMMIT), and finerenone (FINEARTS-HF). These studies represent significant advances in reducing the risk of major adverse cardiovascular events (MACE) and improving metabolic outcomes in heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD), and obstructive sleep apnea (OSA). The congress also comprised sessions on novel and established therapies for managing HFpEF, CKD, and obesity; guidelines for managing CKD and metabolic dysfunction-associated steatotic liver disease (MASLD); organ crosstalk and the development of cardio-kidney-metabolic (CKM) syndrome; precision medicine and person-centered management of diabetes, obesity, cardiovascular disease (CVD) and CKD; early detection of type 1 diabetes (T1D) and strategies to delay its onset; continuous glucose monitoring (CGM) and automated insulin delivery (AID); cardiovascular autonomic neuropathy (CAN) and the diabetic heart; and the role of primary care in the early detection, prevention and management of CKM diseases. The contribution of environmental plastic pollution to CVD risk, the increasing understanding of the efficacy and safety of incretin therapies in the treatment of CKM diseases, and the latest updates on nutrition strategies for CKM management under incretin-based therapies were also topics of interest for a vast audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians, who actively engaged in online discussions. The 11th CVOT Summit will be held virtually on November 20–21, 2025 (http://www.cvot.org)

Arthroscopy vs. MRI for a detailed assessment of cartilage disease in osteoarthritis: diagnostic value of MRI in clinical practice

<p>Abstract</p> <p>Background</p> <p>In patients with osteoarthritis, a detailed assessment of degenerative cartilage disease is important to recommend adequate treatment. Using a representative sample of patients, this study investigated whether MRI is reliable for a detailed cartilage assessment in patients with osteoarthritis of the knee.</p> <p>Methods</p> <p>In a cross sectional-study as a part of a retrospective case-control study, 36 patients (mean age 53.1 years) with clinically relevant osteoarthritis received standardized MRI (sag. T1-TSE, cor. STIR-TSE, trans. fat-suppressed PD-TSE, sag. fat-suppressed PD-TSE, Siemens Magnetom Avanto syngo MR B 15) on a 1.5 Tesla unit. Within a maximum of three months later, arthroscopic grading of the articular surfaces was performed. MRI grading by two blinded observers was compared to arthroscopic findings. Diagnostic values as well as intra- and inter-observer values were assessed.</p> <p>Results</p> <p>Inter-observer agreement between readers 1 and 2 was good (kappa = 0.65) within all compartments. Intra-observer agreement comparing MRI grading to arthroscopic grading showed moderate to good values for readers 1 and 2 (kappa = 0.50 and 0.62, respectively), the poorest being within the patellofemoral joint (kappa = 0.32 and 0.52). Sensitivities were relatively low at all grades, particularly for grade 3 cartilage lesions. A tendency to underestimate cartilage disorders on MR images was not noticed.</p> <p>Conclusions</p> <p>According to our results, the use of MRI for precise grading of the cartilage in osteoarthritis is limited. Even if the practical benefit of MRI in pretreatment diagnostics is unequivocal, a diagnostic arthroscopy is of outstanding value when a grading of the cartilage is crucial for a definitive decision regarding therapeutic options in patients with osteoarthritis.</p

Potential Health-modulating Effects of Isoflavones and Metabolites via Activation of PPAR and AhR

Isoflavones have multiple actions on cell functions. The most prominent one is the activation of estrogen receptors. Other functions are often overlooked, but are equally important and explain the beneficial health effects of isoflavones. Isoflavones are potent dual PPARα/γ agonists and exert anti-inflammatory activity, which may contribute to the prevention of metabolic syndrome, atherosclerosis and various other inflammatory diseases. Some isoflavones are potent aryl hydrocarbon receptor (AhR) agonists and induce cell cycle arrest, chemoprevention and modulate xenobiotic metabolism. This review discusses effects mediated by the activation of AhR and PPARs and casts a light on the concerted action of isoflavones

Eupraxia, a step toward a plasma-wakefield based accelerator with high beam quality

The EuPRAXIA project aims at designing the world's first accelerator based on advanced plasma-wakefield techniques to deliver 5 GeV electron beams that simultaneously have high charge, low emittance and low energy spread, which are required for applications by future user communities. Meeting this challenging objective will only be possible through dedicated effort. Many injection/acceleration schemes and techniques have been explored by means of thorough simulations in more than ten European research institutes. This enables selection of the most appropriate methods for solving each particular problem. The specific challenge of generating, extracting and transporting high charge beams, while maintaining the high quality needed for user applications, are being tackled using innovative approaches. This article highlights preliminary results obtained by the EuPRAXIA collaboration, which also exhibit the required laser and plasma parameters