Predicting the long time dynamic heterogeneity in a supercooled liquid on the basis of short time heterogeneities

We report that the local Debye-Waller factor in a simulated 2D glass-forming mixture exhibits significant spatial heterogeneities and that these short time fluctuations provide an excellent predictor of the spatial distribution of the long time dynamic propensities [Phys.Rev.Lett. 93, 135701 (2004)]. In contrast, the potential energy per particle of the inherent structure does not correlate well with the spatially distributed dynamics

Atomic structure of Mn wires on Si(001) resolved by scanning tunneling microscopy

At submonolayer coverage, Mn forms atomic wires on the Si(001) surface oriented perpendicular to the underlying Si dimer rows. While many other elements form symmetric dimer wires at room temperature, we show that Mn wires have an asymmetric appearance and pin the Si dimers nearby. We find that an atomic configuration with a Mn trimer unit cell can explain these observations due to the interplay between the Si dimer buckling phase near the wire and the orientation of the Mn trimer. We study the resulting four wire configurations in detail using high-resolution scanning tunneling microscopy (STM) imaging and compare our findings with STM images simulated by density functional theory.Comment: 4 pages, 4 figure

Fieber und Lymphadenopathie: Bericht über 4Tularämiefälle

Zusammenfassung: Wir berichten über 4Patienten, die in der Schweiz oder dem grenznahen Ausland an unterschiedlichen Formen der Tularämie erkrankten. Als Gemeinsamkeiten zeigten alle Patienten ein febriles Zustandsbild mit mäßiger bis ausgeprägter laborchemischer Entzündungsreaktion und eine lokoregionäre Lymphadenopathie. Zusätzlich führte bei 3Patienten eine empirisch begonnene Therapie mit β-Laktam-Antibiotika zu keiner Verbesserung der Klinik. Als Infektionsquelle konnte bei 2Patienten eine eindeutige, in einem Fall eine mögliche Korrelation mit einem Zeckenstich eruiert werden. Bei der vierten Patientin blieb der Ursprung der Tularämie ungeklärt. Die Diagnose stützte sich auf eine positive Serologie, eine positive Polymerase-Kettenreaktion (PCR) aus einem Gewebeaspirat oder auf positive Blutkulturen. Die Therapie erfolgte bei 3erwachsenen Patienten mit Ciprofloxacin p.o. über 3Wochen, wobei die Dosierung zwischen 500 und 750mg 2-mal täglich variierte. Bei einem pädiatrischen Patienten wurde die Therapie mit Gentamicin 4mg/kgKG i.v. 1-mal täglich für eine Woche und mit Ciprofloxacin 15mg/kgKG p.o. 2-mal täglich für 2weitere Wochen durchgeführt. Unter adäquater Therapie kam es bei allen Patienten zu einem erfreulichen Krankheitsverlauf mit vollständiger Ausheilung. Bei Patienten mit Fieber und Lymphknotenvergrößerung - insbesondere nach Zeckenstich - muss auch in der Schweiz eine Tularämie in die Differenzialdiagnose einbezogen werden. Als Therapie empfehlen wir eine Medikation mit Ciprofloxacin p.o. für 14-21Tag

Biases affecting injected doses of an experimental drug during clinical trials.

During clinical trials, researchers rarely question nominal doses specified on labels of investigational products, overlooking the potential for inaccuracies that may result when calculating pharmacokinetic and pharmacodynamic parameters. This study evaluated the disparity between nominal doses and the doses actually administered in two Phase I trials of a biosimilar drug. In Trial A, 12 healthy volunteers received various doses of an interferon β-1a biosimilar via either subcutaneous or intravenous injection, prepared by partially emptying 0.53 ml syringes supplied by the manufacturer. In Trial B, 12 volunteers received three different formulations of the drug via intravenous injection (biosimilar with and without albumin and a comparator), followed by multiple subcutaneous injections. In both trials, the dose administered was calculated as D = C × V - losses, where C is the drug concentration assessed using ELISA, V is the volume administered calculated using syringe weighing and losses are deduced from in-vitro experiments. Interferon binding to added albumin and infusion lines was evaluated using a (125)I-interferon tracer with gel-filtration chromatography. In Trial A, measured concentrations were close to the nominal strength indicated by the manufacturer (median bias: -6 %), whereas in Trial B they differed significantly for all three formulations (median biases: +67 %, +73 % and +31 % for the biosimilar with albumin, the biosimilar without albumin and the comparator, respectively). In Trial A, the doses actually administered showed large variability and biases, especially at the lowest doses. Indeed, actually injected volumes differed by as much as 74 % from theoretical volumes - a phenomenon mainly attributed to unnoticed fluid re-aspiration through the syringe needle. This was corrected in Trial B. Interferon was not significantly adsorbed on the infusion lines used for intravenous administration. Its binding to albumin was slow, reaching 50 % after a 16 h incubation. These examples illustrate the importance of assessing the actual doses administered in clinical trials, to ensure accuracy in the determination of clearance, distribution volume, bioavailability and dose-response relationships. Clinicaltrials.gov NCT02515695 (Trial A) and NCT02517788 (Trial B). Registered on 24 July and 5 August 2015, respectively

Gefäßmedizin heute: Die Berner Sicht

Zusammenfassung: Die moderne Behandlung von Gefäßpatienten stellt eine reizvolle und anspruchsvolle Aufgabe dar, welche aufgrund der Komplexität und der Breite des Spektrums heute in interdisziplinären Gefäßzentren durchgeführt werden sollte. Die enge Zusammenarbeit zwischen Gefäßchirurgen und Angiologen hat an der Universität Bern eine lange Tradition. Der vorliegende Artikel legt die grundlegende Philosophie unserer gefäßchirurgisch-angiologischen Freundschaft und Zusammenarbeit dar und schildert deren Umsetzung im klinischen Allta

Dosing regimen of gentamicin in neonates: evaluation of current guidelines based on a large population pharmacokinetic analysis

Objectives: Gentamicin is among the most commonly prescribed antibiotics in newborns, but large interindividual variability in exposure levels exists. Based on a population pharmacokinetic analysis of a cohort of unselected neonates, we aimed to validate current dosing recommendations from a recent reference guideline (Neofax®). Methods: From 3039 concentrations collected in 994 preterm (median gestational age 32.3 weeks, range 24.2-36.5) and 455 term newborns, treated at the University Hospital of Lausanne between 2006 and 2011, a population pharmacokinetic analysis was performed with NONMEM®. Model-based simulations were used to assess the ability of dosing regimens to bring concentrations into targets: trough ≤ 1mg/L and peak ~ 8mg/L. Results: A two-compartment model best characterized gentamicin pharmacokinetics. Model parameters are presented in the table. Body weight, gestational age and postnatal age positively influence clearance, which decreases under dopamine administration. Body weight and gestational age influence the distribution volume. Model based simulations confirm that preterm infants need doses superior to 4 mg/kg, and extended dosage intervals, up to 48 hours for very preterm newborns, whereas most term newborns would achieve adequate exposure under 4 mg/kg q. 24 h. More than 90% of neonates would achieve trough concentrations below 2 mg/L and peaks above 6 mg/L following most recent guidelines. Conclusions: Simulated gentamicin exposure demonstrates good accordance with recent dosing recommendations for target concentration achievement

Eradication of an epidemic methicillin-resistant Staphylococcus aureus (MRSA) from a geriatric university hospital: evidence from a 10-year follow-up

We report on a successful eradication of methicillin-resistant S. aureus (MRSA) after an epidemic in 1992 in the geriatric ward of a tertiary-care hospital. After identification of MRSA in seven patients, all patients and staff members in the geriatric ward underwent screening. A multifaceted intervention plan was implemented: contact isolation, optimization of infection control and decolonization of all MRSA carriers. Thirty-two patients and five staff members were found to be MRSA carriers. Twenty one of 32 (66%) patients and all five staff members were successfully decolonized. Seven of 32 (22%) patients died during the epidemic before decolonization. A couple was discharged with persisting MRSA colonization and two individuals were lost to follow-up. The eradication of the epidemic clone was proven by systematic screenings in 1995 and 1997. Since then, the strain has no longer been identified in our institution, based on epidemiological surveillance and molecular typing of all MRSA strains obtained from any specimen. This study provides strong evidence that long-term eradication of an MRSA epidemic in a hospital is feasible, and endemicity of MRSA after an outbreak can be avoided. The successful bundle approach for eradication of MRSA during an epidemic is expensive, but the long-term benefits likely outweigh the initial heavy use of resource

Adolescents' preference for later school start times

As the chronotype delays progressively throughout puberty, early morning school start times (SSTs) contradict the sleep biology of adolescents. Various studies have demonstrated beneficial effects of later SSTs on sleep and health; however, adolescents' preferences for SSTs have to date never been investigated in detail. The present online survey study aimed to fill this gap and explored influencing factors. A total of 17 high schools in the Canton of Zurich, Switzerland, circulated the survey among their students. Participants were included if they reported their sex, age, and school (n = 5,308). Students indicated whether they preferred later SSTs. Additionally, five predictor blocks were assessed: sociodemographic, school-related, sleep, leisure-time, and health-related characteristics. We applied multivariate logistic regression models with fixed and random effects to predict the preference. The mean (SD) age of the students was 16.09 (1.76) years (65.1% female). The majority (63.2%) endorsed later SSTs with a preferred delay of 55 min (interquartile range 25-75 min). In the multilevel analysis (n = 2,627), sex, mother tongue, sleep characteristics, mobile device use at bedtime, caffeine consumption, and health-related quality of life were significant predictors for the preference. Hence, the majority of adolescents preferred later SSTs, and especially those with sleep or health-related problems. These characteristics have been consistently shown to improve after delaying SSTs. Thus, also from adolescents' view, later SSTs should be considered to improve the adolescents' health