The amplitude of lower leg motor evoked potentials is a reliable measure when controlled for torque and motor task

Abstract : Objectives : Motor evoked potential (MEP) amplitudes have the disadvantage of a high variability when repeatedly assessed. This affects the reliability of MEP amplitude measurements taken during the course of motor incomplete spinal cord injury (iSCI). The study investigated the reliability of anterior tibial (TA) MEP measures controlled for dorsal flexion torque and motor task. Methods : TA MEPs were recorded at 10, 20, 40 and 60% of maximal voluntary contraction (MVC) during a static and dynamic (isometric increase of dorsal flexion torque) motor task. To determine reliability, 20 healthy and five chronic iSCI subjects were tested twice (≥7 days) by the same investigator. Intraclass correlation coefficients (ICCs) were calculated. MEP amplitudes and latencies were compared between 20 healthy and 29 iSCI subjects. Results : The reliability of MEP amplitude was in general good (ICC ≥ 0.52) and was highest during the static task at 40% MVC (ICC = 0.77). The increased facilitation by the dynamic motor task showed the best reliability at 20% MVC (ICC = 0.48). The reliability was good to excellent for MEP latency (0.46 ≥ ICC ≥ 0.81), MVC (ICC ≥ 0.90) and for the TMS threshold required to evoke a MEP response (ICC ≥ 0.77). The torque generated by the MEP response ()0.02 ≥ ICC ≥ 0.55) and the duration of the silent period (0.07 ≥ ICC ≥ 0.50) were not reliable. Both MEP amplitudes and latencies differed significantly between healthy and iSCI subjects. Conclusions : Controlling for torque generation and motor task establishes a reliability of TA MEP amplitudes that is sufficient for longitudinal assessments in motor incomplete SC

PLK1-dependent phosphorylation restrains EBNA2 activity and lymphomagenesis in EBV-infected mice

While Epstein-Barr virus (EBV) establishes a life-long latent infection in apparently healthy human immunocompetent hosts, immunodeficient individuals are at particular risk to develop lymphoproliferative B-cell malignancies caused by EBV. A key EBV protein is the transcription factor EBV nuclear antigen 2 (EBNA2), which initiates B-cell proliferation. Here, we combine biochemical, cellular, and in vivo experiments demonstrating that the mitotic polo-like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain, and thereby inhibits its biological activity. EBNA2 mutants that impair PLK1 binding or prevent EBNA2 phosphorylation are gain-of-function mutants. They exhibit enhanced transactivation capacities, accelerate the proliferation of infected B cells, and promote the development of monoclonal B-cell lymphomas in infected mice. Thus, PLK1 coordinates the activity of EBNA2 to attenuate the risk of tumor incidences in favor of the establishment of latency in the infected but healthy host

Time- and spatially-resolved magnetization dynamics driven by spin-orbit torques

Current-induced spin-orbit torques (SOTs) represent one of the most effective ways to manipulate the magnetization in spintronic devices. The orthogonal torque-magnetization geometry, the strong damping, and the large domain wall velocities inherent to materials with strong spin-orbit coupling make SOTs especially appealing for fast switching applications in nonvolatile memory and logic units. So far, however, the timescale and evolution of the magnetization during the switching process have remained undetected. Here, we report the direct observation of SOT-driven magnetization dynamics in Pt/Co/AlO$_x$ dots during current pulse injection. Time-resolved x-ray images with 25 nm spatial and 100 ps temporal resolution reveal that switching is achieved within the duration of a sub-ns current pulse by the fast nucleation of an inverted domain at the edge of the dot and propagation of a tilted domain wall across the dot. The nucleation point is deterministic and alternates between the four dot quadrants depending on the sign of the magnetization, current, and external field. Our measurements reveal how the magnetic symmetry is broken by the concerted action of both damping-like and field-like SOT and show that reproducible switching events can be obtained for over $10^{12}$ reversal cycles

Time- and spatially-resolved magnetization dynamics driven by spin-orbit torques

Current-induced spin-orbit torques (SOTs) represent one of the most effective ways to manipulate the magnetization in spintronic devices. The orthogonal torque-magnetization geometry, the strong damping, and the large domain wall velocities inherent to materials with strong spin-orbit coupling make SOTs especially appealing for fast switching applications in nonvolatile memory and logic units. So far, however, the timescale and evolution of the magnetization during the switching process have remained undetected. Here, we report the direct observation of SOT-driven magnetization dynamics in Pt/Co/AlO$_x$ dots during current pulse injection. Time-resolved x-ray images with 25 nm spatial and 100 ps temporal resolution reveal that switching is achieved within the duration of a sub-ns current pulse by the fast nucleation of an inverted domain at the edge of the dot and propagation of a tilted domain wall across the dot. The nucleation point is deterministic and alternates between the four dot quadrants depending on the sign of the magnetization, current, and external field. Our measurements reveal how the magnetic symmetry is broken by the concerted action of both damping-like and field-like SOT and show that reproducible switching events can be obtained for over $10^{12}$ reversal cycles

KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection

Funding Information: This research was supported in part by Cancer Research Switzerland , Switzerland ( KFS-4091-02-2017 ); KFSP-PrecisionMS and HMZ ImmunoTargET of the University of Zurich , Switzerland; the Cancer Research Center Zurich , Switzerland; the Vontobel Foundation , Switzerland; the Baugarten Foundation , Switzerland; the Sobek Foundation , Germany; the Swiss Vaccine Research Institute , Switzerland; Roche , Switzerland; Novartis , Switzerland; and the Swiss National Science Foundation , Switzerland ( 310030B_182827 and CRSII5_180323 ). A.M.M. was funded by a National Institutes of Health , United States, grant ( R01 CA189806 ). N.C. was supported by a career advancement grant from the University of Zurich , Switzerland ( FK-18-026 ). D.M. and M.B. were supported by MD-PhD fellowships from the Swiss National Science Foundation , Switzerland, and the Swiss Academy of Medical Sciences , Switzerland ( 323530_145247 and 323630_19938 ).Peer reviewedPublisher PD

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

BACKGROUND Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with 5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research

Work transformation in banks: the impacts on workers' identity and well-being

reservedDa qualche anno la stampa e le organizzazioni sindacali denunciano gli alti livelli di stress e malessere all’interno del settore bancario. Partendo da questa constatazione, la tesi propone uno studio dell’evoluzione del sistema bancario italiano concentrandosi in particolare sui cambiamenti del lavoro nelle filiali. L’obiettivo è quello di capire come le modifiche organizzative degli istituti impattano sui dipendenti, variando le mansioni, le interazioni in agenzia con clienti e colleghi, il significato attribuito al lavoro e la percezione di sé stessi come consulenti bancari. In ultima analisi, si cercherà di capire se tutto ciò è percepito dai lavoratori come fonte di stress e malessere. Lo studio prende in considerazione due aziende bancarie a rilevanza nazionale e si basa su interviste semistrutturate a lavoratori e lavoratrici con ruoli di consulenza in filiali all’interno del territorio della regione Veneto. A ciò si aggiunge un diario etnografico frutto del mio ruolo di dipendente e rappresentante sindacale all’interno del settore

Lungentransplantation bei Patienten mit interstitieller Lungenerkrankung/idiopathisch pulmonaler Fibrose

Zusammenfassung. Die Lungentransplantation ist eine etablierte Therapieoption bei fortgeschrittenen Lungenerkrankungen. Interstitielle Lungenerkrankungen und insbesonders die idiopathisch pulmonale Fibrose (IPF) haben im Vergleich zu anderen Lungenerkrankungen mit Indikation zur Lungentransplantaton im Allgemeinen eine schlechtere Prognose. Eine frühzeitige Zuweisung an ein Lungentransplantationszentrum zur Evaluation einer möglichen Lungentransplantation sollte deshalb bei histologischem und/oder radiologischem Nachweis einer usual interstital pneumonitis (UIP) erfolgen, aufgrund der zu erwartenden rapiden Progredienz der Pneumopathie. Abstract. Lung transplantation is an established therapy for advanced lung disease. Among the common disease indications for lung transplantation, patients with interstitial lung disease, in particular, idiopathic pulmonary fibrosis (IPF), have the worst prognosis. Thus referral to a transplant center should ideally be realised at the time of diagnosis of usual interstitial pneumonitis (UIP), regardless of lung function, in order to carry out a through initial assessment and evaluation