Do pneumatic tube transport systems transmit potential pathogens? A hygienic risk assessment in a university hospital.

BACKGROUND: Prompted by an outbreak of vancomycin-resistant enterococci (VRE) in a medical facility, this study examined a pneumatic tube transport system (PTS) as a potential transmission channel. METHOD: Samples from the receiving station and entry racks were gathered via smear technique. Sponges used for PTS decontamination were soaked with 0.89% NaCl and transported through the channel. Micro-organisms were recovered from the tubes and cleaning sponges using a wash-away technique. Air sampling was performed at the receiving station in order to detect any airborne contamination. Tubes were artificially inoculated with Escherichia coli K12 NCTC 10538 and Staphylococcus epidermidis DSM 20044 and sent through the PTS to investigate channel contamination. RESULTS: No pathogens were detected in effluent air from the PTS or in tubes during routine operation. Entry racks for the test tubes were contaminated with coagulase-negative staphylococci (CNS), aerobic bacilli, moulds and vancomycin-susceptible Enterococcus faecium. E. coli proved to be unsuitable for detecting bacterial transmission by the PTS due to low persistence, but S. epidermidis was more resilient. After sending contaminated test tubes through the PTS, levels of S. epidermidis only decreased marginally. Subsequently, sponges soaked with disinfectant solution were put through the system and these eliminated S. epidermidis completely from the first attempt. DISCUSSION: Routine hygienic maintenance of the PTS makes pathogen transmission highly unlikely, although entry racks should be disinfected regularly. Any involvement of the PTS in the VRE outbreak at the study institution was unlikely.

Nonequilibrium depletion interactions in active microrheology.

Entropic depletion forces arise between mesoscopic bodies that are immersed in a suspension of macromolecules, such as colloid-polymer mixtures. Here we consider the case of a driven colloidal probe in the presence of another, passive colloidal particle, both solvated in an ideal bath of small spherical particles. We calculate the nonequilibrium forces mediated by the depletants on the two colloidal particles within a dynamical superposition approximation (DSA) scheme. In order to assess the quality of this approximation, and to obtain the colloidal microstructure around the driven probe, we corroborate our theoretical results with Brownian dynamics simulations.

Driven Brownian particle as a paradigm for a nonequilibrium heat bath: Effective temperature and cyclic work extraction.

We apply the concept of a frequency-dependent effective temperature based on the fluctuation-dissipation ratio to a driven Brownian particle in a nonequilibrium steady state. Using this system as a thermostat for a weakly coupled harmonic oscillator, the oscillator thermalizes according to a canonical distribution at the respective effective temperature across the entire frequency spectrum. By turning the oscillator from a passive thermometer into a heat engine, we realize the cyclic extraction of work from a single thermal reservoir, which is feasible only due to its nonequilibrium nature.

[Spectrum of pathogens in postoperative complications of visceral surgery : The problem of multidrug resistance]. / Erregerspektrum postoperativer Komplikationen in der Viszeralchirurgie : Das Problem der Multiresistenz.

In general surgery the etiology of surgical site infections has not significantly changed over the last 30 years. Gram-positive bacteria, e.g. coagulase negative staphylococci (CNS), Staphylococcus aureus and Enterococcus spp. as well as Gram-negative bacteria, e.g. Escherichia coli, Enterobacter spp., Klebsiella spp. and Pseudomonas aeruginosa, are the most common findings. Although in general surgery 10% of the S. aureus causing postoperative wound infections were methicillin resistant (MRSA), no cases of multidrug-resistant Gram-negative (MRGN) bacteria were reported. Yeasts (particularly Candida spp.) are rarely the pathogen causing surgical site infections (≤3%) and concomitant risk factors are typical (e.g. diabetes, chemotherapy, immunosuppression and malnutrition). Viruses are rarely the cause of surgical site infections. Transmission can occur by HBV, HCV or HIV positive surgical staff or in organ transplantations and postoperative reactivation of persistent infections is possible (especially for HBV, HCV, CMV, EBV and HIV). The principles for prevention of surgical site infections are dealt with as consequences of preoperative colonization by MRSA, methicillin-sensitive S. aureus (MSSA) and MRGN and reviewed with respect to screening, perioperative antibiotic prophylaxis and decolonization. In nosocomial peritonitis, the selection of antibiotics should consider previous antibiotic treatment. A single intra-abdominal detection of Candida spp. usually does not require antimycotic treatment in postoperatively stable and immunocompetent patients but is recommended in severe community-acquired or nosocomial peritonitis. Viral infections can be avoided by screening of organ donors and serological surveillance of surgery personnel.

Control of force through feedback in small driven systems.

Controlling a time-dependent force applied to single molecules or colloidal particles is crucial for many types of experiments. Since in optical tweezers the primary controlled variable is the position of the trap, imposing a target force requires an active feedback process. We analyze this feedback process for the paradigmatic case of a nonequilibrium steady state generated by a dichotomous force protocol, first theoretically for a colloidal particle in a harmonic trap and then with both simulations and experiments for a long DNA hairpin. For the first setup, we find there is an optimal feedback gain separating monotonic from oscillatory response, whereas a too strong feedback leads to an instability. For the DNA molecule, reaching the target force requires substantial feedback gain since weak feedback cannot overcome the tendency to relax towards the equilibrium force.

Moraxella catarrhalis induces CEACAM3-Syk-CARD9-dependent activation of human granulocytes.

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease in adults. In such patients, increased numbers of granulocytes are present in the airways, which correlate with bacteria-induced exacerbations and severity of the disease. Our study investigated whether the interaction of M. catarrhalis with the human granulocyte-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-3 is linked to NF-κB activation, resulting in chemokine production. Granulocytes from healthy donors and NB4 cells were infected with M. catarrhalis in the presence of different inhibitors, blocking antibodies and siRNA. The supernatants were analysed by enzyme-linked immunosorbent assay for chemokines. NF-κB activation was determined using a luciferase reporter gene assay and chromatin-immunoprecipitation. We found evidence that the specific engagement of CEACAM3 by M. catarrhalis ubiquitous surface protein A1 (UspA1) results in the activation of pro-inflammatory events, such as degranulation of neutrophils, ROS production and chemokine secretion. The interaction of UspA1 with CEACAM3 induced the activation of the NF-κB pathway via Syk and the CARD9 pathway and was dependent on the phosphorylation of the CEACAM3 ITAM-like motif. These findings suggest that the CEACAM3 signalling in neutrophils is able to specifically modulate airway inflammation caused by infection with M. catarrhalis.

Discontinuous thinning in active microrheology of soft complex matter.

Employing theory and numerical simulations, we demonstrate discontinuous force thinning due to the driven motion of an external probe in a host medium. We consider two cases: an ideal structureless medium (modeling ultrasoft materials such as polymer melts) and a dilute bath of interacting repulsive particles. When the driving of the probe exceeds a critical force, the microviscosity of the medium drops abruptly by about an order of magnitude. This phenomenon occurs for strong attractive interactions between a large probe and a sufficiently dense host medium.

Measuring fast stochastic displacements of bio-membranes with dynamic optical displacement spectroscopy.

Stochastic displacements or fluctuations of biological membranes are increasingly recognized as an important aspect of many physiological processes, but hitherto their precise quantification in living cells was limited due to a lack of tools to accurately record them. Here we introduce a novel technique--dynamic optical displacement spectroscopy (DODS), to measure stochastic displacements of membranes with unprecedented combined spatiotemporal resolution of 20 nm and 10 µs. The technique was validated by measuring bending fluctuations of model membranes. DODS was then used to explore the fluctuations in human red blood cells, which showed an ATP-induced enhancement of non-Gaussian behaviour. Plasma membrane fluctuations of human macrophages were quantified to this accuracy for the first time. Stimulation with a cytokine enhanced non-Gaussian contributions to these fluctuations. Simplicity of implementation, and high accuracy make DODS a promising tool for comprehensive understanding of stochastic membrane processes.

[Screening for cancer]. / Screening für Krebserkrankungen.

A low birth rate in addition to an increasing life expectancy within the context of an aging population characterize the current demographic situation in Germany. Cancer is primarily a disease of old age and the frequency increases with an expanding older population. In 2013, cancer was the second most common cause of death in Germany. With the aid of screening examinations cancer should be detected in the early stages so that suitable therapeutic measures can be initiated. In Germany, screening is currently offered for breast, cervical, colorectal, skin and prostate cancer and is covered by the statutory health insurance. Mammography screening is the only organized screening program in Germany. Eligible women are regularly invited to attend this program, which is not the case for the other types of cancer screening. In accordance with the Cancer Screening and Registry Act (KFRG) of 2013, colorectal and cervical cancer screening will also be implemented as organized screening programs in the future. As is the case in the mammography screening program, those eligible to participate will receive an invitation letter and the new programs are to be continually monitored, documented and evaluated.

Unifying three perspectives on information processing in stochastic thermodynamics.

So far, feedback-driven systems have been discussed using (i) measurement and control, (ii) a tape interacting with a system, or (iii) by identifying an implicit Maxwell demon in steady-state transport. We derive the corresponding second laws from one master fluctuation theorem and discuss their relationship. In particular, we show that both the entropy production involving mutual information between system and controller and the one involving a Shannon entropy difference of an information reservoir like a tape carry an extra term different from the usual current times affinity. We, thus, generalize stochastic thermodynamics to the presence of an information reservoir.

[Early detection of cervical cancer in Germany: evidence and implementation]. / Früherkennung des Zervixkarzinoms in Deutschland : Evidenz und Umsetzung.

Cervical cancer is the third most common cancer among women worldwide, with an estimated 529,000 new cases in 2008. The incidence of cervical cancer in Germany is still among the highest in Western Europe. For more than 40 years women in Germany have had legal and free access to a conventional cytologic smear test starting at the age of 20 years. The introduction of the Pap smear subsequently led to a reduction in the incidence and mortality of cervical cancer. However, the low sensitivity of the Pap smear and the evidence regarding human papillomavirus (HPV) in the context of cervical cancer have led to a critical view of the existing early detection of cervical cancer. In the meantime, new screening methods have been developed and different HPV tests, liquid-based cytology, and novel biomarkers have become available. Several randomized studies have investigated HPV testing as a primary cervical cancer screening test, generating a large body of evidence. It is expected that a combination of HPV testing and cytology will improve cervical cancer screening. In the near future, the early detection of cervical cancer in Germany will be restructured on the basis of the German National Cancer Plan as well as the new Cancer Screening and Registers Act (KFRG). The European guidelines for quality assurance in cervical cancer screening will be taken into account, and an organized, population-based, and quality-assured cervical cancer screening program will be implemented.

Stochastic thermodynamics of fluctuating density fields: non-equilibrium free energy differences under coarse-graining.

We discuss the stochastic thermodynamics of systems that are described by a time-dependent density field, for example, simple liquids and colloidal suspensions. For a time-dependent change of external parameters, we show that the Jarzynski relation connecting work with the change of free energy holds if the time evolution of the density follows the Kawasaki-Dean equation. Specifically, we study the work distributions for the compression and expansion of a two-dimensional colloidal model suspension implementing a practical coarse-graining scheme of the microscopic particle positions. We demonstrate that even if coarse-grained dynamics and density functional do not match, the fluctuation relations for the work still hold albeit for a different, apparent, change of free energy.

Information-theoretic versus thermodynamic entropy production in autonomous sensory networks.

For sensory networks, we determine the rate with which they acquire information about the changing external conditions. Comparing this rate with the thermodynamic entropy production that quantifies the cost of maintaining the network, we find that there is no universal bound restricting the rate of obtaining information to be less than this thermodynamic cost. These results are obtained within a general bipartite model consisting of a stochastically changing environment that affects the instantaneous transition rates within the system. Moreover, they are illustrated with a simple four-states model motivated by cellular sensing. On the technical level, we obtain an upper bound on the rate of mutual information analytically and calculate this rate with a numerical method that estimates the entropy of a time series generated with a simulation.

Noninvasive measurement of dissipation in colloidal systems.

According to Harada and Sasa [Phys. Rev. Lett. 95, 130602 (2005)], heat production generated in a nonequilibrium steady state can be inferred from measuring response and correlation functions. In many colloidal systems, however, it is a nontrivial task to determine response functions, whereas details about spatial steady state trajectories are easily accessible. Using a simple conditional averaging procedure, we show how this fact can be exploited to reliably evaluate average heat production. We test this method using Brownian dynamics simulations, and apply it to experimental data of an interacting driven colloidal system.

Role of hidden slow degrees of freedom in the fluctuation theorem.

The validity of the fluctuation theorem for entropy production as deduced from the observation of trajectories implicitly requires that all slow degrees of freedom are accessible. We experimentally investigate the role of hidden slow degrees of freedom in a system of two magnetically coupled driven colloidal particles. The apparent entropy production based on the observation of just one particle obeys a fluctuation theorem-like symmetry with a slope of 1 in the short time limit. For longer times, we find a constant slope, but different from 1. We present theoretical arguments for a generic linear behavior both for small and large apparent entropy production but not necessarily throughout. By fine-tuning experimental parameters, such an intermediate nonlinear behavior can indeed be recovered in our system as well.

[Effect of botulinum toxin type B on residual limb sweating and pain. Is there a chance for indirect phantom pain reduction by improved prosthesis use?]. / Wirkung von Botulinumtoxin Typ B auf Stumpfschwitzen und Stumpfschmerzen. Besteht die Chance der indirekten Phantomschmerzreduktion durch bessere Prothesennutzung?

OBJECTIVES: Hyperhidrosis of a residual limb after amputation is one of the most common reasons for impaired prosthesis use and quality of life and affects 30-50% of all amputees causing skin irritation in about 25%. Thus the probability of residual limb pain increases in addition to an increased likelihood of phantom pain due to shorter duration of prothesis use. Development of both types of pain was studied following treatment of hyperhidrosis in 9 amputees. DESIGN: A total of 9 lower limb amputees received injections of 1750 units of botulinum toxin type B (BTX-B) for the treatment of hyperhidrosis of a residual limb (20 intracutaneous injections each). Prior to injections and 4 weeks and 3 months afterwards, patients rated the impairments regarding residual limb pain, phantom pain and sweating of the residual limb. Furthermore the duration of use of the prosthetic device and quality of life were rated on a numeric rating scale (NRS 0-10). RESULTS: Stump pain (n=9) was highly significantly reduced after 3 months (baseline: NRS 5; 4 weeks: NRS 4, p=0.109; 3 months: NRS 3, p=0.008) and also a tendency for phantom pain after 3 months (baseline NRS 5; 3 months: NRS 3; p=0.109). Sweating of the residual limb prior to BTX-B application was rated as a median 7 on the NRS scale with significant improvements after 4 weeks (NRS 3, p=0.027) and 3 months (NRS 3, p=0.020). Impaired duration of prothesis use improved from NRS 8 to NRS 2 (4 weeks; p=0.023) and NRS 3 (3 months; p=0.023) as well as the quality of life (p=0.016, p=0.023, respectively). CONCLUSIONS: Residual limb pain improved 3 months after intracutaneous, low-dose BTX-B in a trial with 9 patients and also phantom pain by tendency. Sweating of the residual limb was significantly reduced, probably thereby improving the duration of prothesis use. Larger studies should confirm these findings and conclusions.

Micro-capsules in shear flow.

This paper deals with flow-induced shape changes of elastic capsules. The state of the art concerning both theory and experiments is briefly reviewed starting with dynamically induced small deformation of initially spherical capsules and the formation of wrinkles on polymerized membranes. Initially non-spherical capsules show tumbling and tank-treading motion in shear flow. Theoretical descriptions of the transition between these two types of motion assuming a fixed shape are at odds with the full capsule dynamics obtained numerically. To resolve the discrepancy, we expand the exact equations of motion for small deformations and find that shape changes play a dominant role. We classify the dynamical phase transitions and obtain numerical and analytical results for the phase boundaries as a function of viscosity contrast, shear and elongational flow rate. We conclude with perspectives on time-dependent flow, on shear-induced unbinding from surfaces, on the role of thermal fluctuations and on applying the concepts of stochastic thermodynamics to these systems.

Stochastic thermodynamics of single enzymes and molecular motors.

For a single enzyme or molecular motor operating in an aqueous solution of non-equilibrated solute concentrations, a thermodynamic description is developed on the level of an individual trajectory of transitions between states. The concept of internal energy, intrinsic entropy and free energy for states follows from a microscopic description using one assumption on time scale separation. A first-law energy balance then allows the unique identification of the heat dissipated in one transition. Consistency with the second law on the ensemble level enforces both stochastic entropy as third contribution to the entropy change involved in one transition and the local detailed balance condition for the ratio between forward and backward rates for any transition. These results follow without assuming weak coupling between the enzyme and the solutes, ideal solution behavior or mass action law kinetics. The present approach highlights both the crucial role of the intrinsic entropy of each state and the physically questionable role of chemiostats for deriving the first law for molecular motors subject to an external force under realistic conditions.

Elastic capsules in shear flow: analytical solutions for constant and time-dependent shear rates.

We investigate the dynamics of microcapsules in linear shear flow within a reduced model with two degrees of freedom. In previous work for steady shear flow, the dynamic phases of this model, i.e. swinging, tumbling and intermittent behaviour, have been identified using numerical methods. In this paper, we integrate the equations of motion in the quasi-spherical limit analytically for time-constant and time-dependent shear flow using matched asymptotic expansions. Using this method, we find analytical expressions for the mean tumbling rate in general time-dependent shear flow. The capsule dynamics is studied in more detail when the inverse shear rate is harmonically modulated around a constant mean value for which a dynamic phase diagram is constructed. By a judicious choice of both modulation frequency and phase, tumbling motion can be induced even if the mean shear rate corresponds to the swinging regime. We derive expressions for the amplitude and width of the resonance peaks as a function of the modulation frequency.

Two-dimensional fluctuating vesicles in linear shear flow.

The stochastic motion of a two-dimensional vesicle in linear shear flow is studied at finite temperature. In the limit of small deformations from a circle, Langevin-type equations of motion are derived, which are highly nonlinear due to the constraint of constant perimeter length. These equations are solved in the low-temperature limit and using a mean-field approach, in which the length constraint is satisfied only on average. The constraint imposes non-trivial correlations between the lowest deformation modes at low temperature. We also simulate a vesicle in a hydrodynamic solvent by using the multi-particle collision dynamics technique, both in the quasi-circular regime and for larger deformations, and compare the stationary deformation correlation functions and the time autocorrelation functions with theoretical predictions. Good agreement between theory and simulations is obtained.