A pseudospectral method for the simulation of 3-D ultrasonic and seismic waves in heterogeneous poroelastic borehole environments

We present a novel approach for the comprehensive, flexible and accurate simulation of poroelastic wave propagation in 3-D cylindrical coordinates. An important application of this method is the realistic modelling of complex seismic wave phenomena in fluid-filled boreholes, which represents a major, as of yet largely unresolved, problem in exploration geophysics. To this end, we consider a numerical mesh consisting of three concentric domains representing the borehole fluid in the centre followed by the mudcake and/or casing, and the surrounding porous formation. The spatial discretization is based on a Chebyshev expansion in the radial direction and Fourier expansions in the vertical and azimuthal directions as well as a Runge–Kutta integration scheme for the time evolution. Trigonometric interpolation and a domain decomposition method based on the method of characteristics are used to match the boundary conditions at the fluid/porous-solid and porous-solid/porous-solid interfaces as well as to reduce the number of gridpoints in the innermost domain for computational efficiency. We apply this novel modelling approach to the particularly challenging scenario of near-surface borehole environments. To this end, we compare 3-D heterogeneous and corresponding rotationally invariant simulations, assess the sensitivity of Stoneley waves to formation permeability in the presence of a casing and evaluate the effects of an excavation damage zone behind a casing on sonic log recordings. Our results indicate that only first arrival times of fast modes are reasonably well described by rotationally invariant approximations of 3-D heterogenous media. We also find that Stoneley waves are indeed remarkably sensitive to the average permeability behind a perforated PVC casing, and that the presence of an excavation damage zone behind a casing tends to dominate the overall signature of recorded seismograms

Agreement of benchmarking high antimicrobial usage farms based on either animal treatment index or number of national defined daily doses

Introduction: While treatment frequency as an indicator of antimicrobial consumption is often assessed using defined doses, it can also be calculated directly as an Animal Treatment Index (ATI). In this study, the correlation of calculating antimicrobial usage on Swiss pig farms using either national Defined Daily Doses (DDDch) or an ATI (number of treatments per animal per year) and the agreement between the different methods for the identification of high usage farms were investigated. Material and Methods: The antimicrobial consumption of 893 Swiss pig herds was calculated separately for suckling piglets, weaned piglets, fattening pigs, lactating and gestating sows using the indicators nDDDch (number of DDDch) per animal per year and ATI. Correlations between the indicators were investigated by calculating Spearman's Rho coefficients. The 5, 10, and 25% highest usage farms were determined by applying both methods and the interrater reliability was described using Cohen's Kappa coefficients and visualized by Bland-Altman plots. Results: The Spearman's Rho coefficients showed strong correlations (r > 0.5) between nDDDch/animal/year and ATI. The lowest coefficient was shown for the correlation of both indicators in gestating sows (r = 0.657) and the highest in weaned piglets (r = 0.910). Kappa coefficients identifying high usage farms were the highest in weaned piglets (k = 0.71, 0.85, and 0.91, respectively for 5, 10, and 25% most frequent users) and the lowest in gestating sows (k = 0.54, 0.58, and 0.55 for 5, 10, and 25% most frequent users). Conclusions: In general, the investigated indicators showed strong correlations and a broad agreement in terms of the calculated levels of antimicrobial usage and the identification of high usage farms. Nevertheless, a certain proportion of the farms were defined differently depending on the indicator used. These differences varied by age category and were larger in all age categories except weaned piglets when a higher percentage benchmark was used to define high usage farms. These aspects should be considered when designing scientific studies or monitoring systems and considering which indicator to use

Effect of herd health management on the prevalence of Postpartum Dysgalaktie Syndrome (PPDS) and the treatment incidence

The Postpartum Dysgalaktie Syndrome (PPDS) also known as metritis agalactia mastitis (MMA), is considered the most common disease of the sow after farrowing. The reasons for PPDS are multifactorial and are to be found in the areas of management and hygiene, feeding, water supply and animal specific factors such as body condition and age of the sows. In this study a veterinary herd health management was carried out in 28 pig farms with PPDS, with the aim to reduce the PPDS prevalence and animal treatment incidence (TI). In 20 of 28 problem farms the PPDS-prevalence could be decreased from 37.4% (± 21.8%) to 24.5% (± 14.1%). The TI was not significantly reduced. The most effective procedures to reduce the PPDS-prevalence were the use of a prepartal transition feed, optimizing the PPDSdiagnostic and the use of nonsteroidal antiinflammatory drugs (NSAID) and oxytocin in the PPDS-treatment

Investigation of Different Library Preparation and Tissue of Origin Deconvolution Methods for Urine and Plasma cfDNA Methylome Analysis.

Methylation sequencing is a promising approach to infer the tissue of origin of cell-free DNA (cfDNA). In this study, a single- and a double-stranded library preparation approach were evaluated with respect to their technical biases when applied on cfDNA from plasma and urine. Additionally, tissue of origin (TOO) proportions were evaluated using two deconvolution methods. Sequencing cfDNA from urine using the double-stranded method resulted in a substantial within-read methylation bias and a lower global methylation (56.0% vs. 75.8%, p ≤ 0.0001) compared to plasma cfDNA, both of which were not observed with the single-stranded approach. Individual CpG site-based TOO deconvolution resulted in a significantly increased proportion of undetermined TOO with the double-stranded method (urine: 32.3% vs. 1.9%; plasma: 5.9% vs. 0.04%; p ≤ 0.0001), but no major differences in proportions of individual cell types. In contrast, fragment-level deconvolution led to multiple cell types, with significantly different TOO proportions between the two methods. This study thus outlines potential limitations of double-stranded library preparation for methylation analysis of cfDNA especially for urinary cfDNA. While the double-stranded method allows jagged end analysis in addition to TOO analysis, it leads to significant methylation bias in urinary cfDNA, which single-stranded methods can overcome

High-power long-pulse second harmonic generation and optical damage with free-running Nd : YAG laser

Frequency doubling with a free-running long-pulse Nd:YAG laser and LBO or KTP nonlinear crystals yields conversion efficiency of up to 17.5% and 162 W peak power in the second harmonic. This efficiency is obtained for a TEM00 beam with rectangular temporal pulse shape of 50 to 400 s. To our knowledge, this is the highest second-harmonic generation (SHG) efficiency reported for the long-pulse free-running configuration. The efficiency is limited by optical damage with much lower threshold than in the Q-switch domain. The damage is preceded by a saturation effect of the SHG efficiency. Both wavelengths (fundamental and second-harmonic) are necessary for the creation of the catastrophic damage. We present first evidence for a mechanism that involves creation of transient absorption centers by the second-harmonic radiation due to multiphoton absorption. Absorption of the fundamental wave at these centers leads to local heating and ultimately catastrophic damage

Comparison of methods for donor-derived cell-free DNA quantification in plasma and urine from solid organ transplant recipients.

In allograft monitoring of solid organ transplant recipients, liquid biopsy has emerged as a novel approach using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma. Despite early clinical implementation and analytical validation of techniques, direct comparisons of dd-cfDNA quantification methods are lacking. Furthermore, data on dd-cfDNA in urine is scarce and high-throughput sequencing-based methods so far have not leveraged unique molecular identifiers (UMIs) for absolute dd-cfDNA quantification. Different dd-cfDNA quantification approaches were compared in urine and plasma of kidney and liver recipients: A) Droplet digital PCR (ddPCR) using allele-specific detection of seven common HLA-DRB1 alleles and the Y chromosome; B) high-throughput sequencing (HTS) using a custom QIAseq DNA panel targeting 121 common polymorphisms; and C) a commercial dd-cfDNA quantification method (AlloSeq® cfDNA, CareDx). Dd-cfDNA was quantified as %dd-cfDNA, and for ddPCR and HTS using UMIs additionally as donor copies. In addition, relative and absolute dd-cfDNA levels in urine and plasma were compared in clinically stable recipients. The HTS method presented here showed a strong correlation of the %dd-cfDNA with ddPCR (R 2 = 0.98) and AlloSeq® cfDNA (R 2 = 0.99) displaying only minimal to no proportional bias. Absolute dd-cfDNA copies also correlated strongly (τ = 0.78) between HTS with UMI and ddPCR albeit with substantial proportional bias (slope: 0.25; 95%-CI: 0.19-0.26). Among 30 stable kidney transplant recipients, the median %dd-cfDNA in urine was 39.5% (interquartile range, IQR: 21.8-58.5%) with 36.6 copies/μmol urinary creatinine (IQR: 18.4-109) and 0.19% (IQR: 0.01-0.43%) with 5.0 copies/ml (IQR: 1.8-12.9) in plasma without any correlation between body fluids. The median %dd-cfDNA in plasma from eight stable liver recipients was 2.2% (IQR: 0.72-4.1%) with 120 copies/ml (IQR: 85.0-138) while the median dd-cfDNA copies/ml was below 0.1 in urine. This first head-to-head comparison of methods for absolute and relative quantification of dd-cfDNA in urine and plasma supports a method-independent %dd-cfDNA cutoff and indicates the suitability of the presented HTS method for absolute dd-cfDNA quantification using UMIs. To evaluate the utility of dd-cfDNA in urine for allograft surveillance, absolute levels instead of relative amounts will most likely be required given the extensive variability of %dd-cfDNA in stable kidney recipients

Intelligent Pinhole with Sub-Micrometer Resolution

An intelligent pinhole for confocal microscopy consisting of four position controlled blades forming a rectangular aperture from 3x3μm to 500 x 500 μm was built. This aperture can be positioned without drift under computer control in a positioning range with a sub-micrometer precision. Each blade is suspended by an elastic hinges and moved by a linear magnetic actuator. An integrated position transducer with a reproducibility of better than 40 nm allows a settling time of less than 75 ms. The whole pinhole system is small sized (40x40x20 mm) with an electrical consumption of less than 2W. A first application in a scanning confocal microscope demonstrated the usefulness of such a micro-opto-mechanical system

Project PathoPig—A practical approach to strengthen post mortem analyses and early detection of pig diseases and zoonoses

Post mortem examinations are important for early detection and diagnosis of animal diseases and zoonoses. Over the last ten years, the number of necropsies in livestock has decreased considerably in Switzerland. To counteract this decline, the Federal Food Safety and Veterinary Office (FSVO) launched a project in 2014 called PathoPig. The aim is to evaluate the significance of pathologic-anatomical examinations for early detection of pig diseases and to investigate the impact of the findings on the improvement of pig health. Pig producers can participate if at least one of the following criteria is fulfilled: high morbidity and/or high mortality, unusual clinical signs, recurrent problems of unknown aetiology resistant to therapy or increased use of antimicrobials. Accordingly, the veterinarian examines the herd, fills in a standardised anamnesis protocol and submits one to three pigs representing the health problem to a designated pathology laboratory. After post mortem examination, the veterinarian offers specific recommendations to the farmer. Three to six months later, the Swiss Pig Health Service (SPHS) follows up the success of the veterinary recommendations. In 2014, 371 farms submitted pigs for PathoPig. In 84% of these cases, a conclusive diagnosis was obtained. In 56% of the cases, gastrointestinal problems were determined, most often (44%) caused by pathogenic Escherichia coli. In more than 80% of the cases, the animal health status could be improved considerably after the veterinary consultation. Increased post mortem examinations allowed more specific therapeutic treatments and management recommendations. Additionally, an improvement of collaboration between diagnostic laboratories, veterinarians and producers was achieved, thereby strengthening disease awareness and early detection of pig diseases and zoonoses in Switzerland

Tacrolimus monitoring in hair samples of kidney transplant recipients

BackgroundCalcineurin inhibitors, including tacrolimus, remain a cornerstone of immunosuppressive therapy after kidney transplantation. However, the therapeutic window is narrow, and nephrotoxic side effects occur with overdose, while the risk of alloimmunization and graft rejection increases with underdose. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) allows quantification of tacrolimus in biological samples from patients. This study investigates the feasibility of quantifying tacrolimus in scalp hair from kidney transplant (KT) recipients and correlates hair tacrolimus concentrations with tacrolimus dosage and blood trough levels. The aim was to provide proof-of-principle for hair tacrolimus drug monitoring in KT recipients.MethodSingle-center prospective study between September 9, 2021 and December 4, 2021, including KT recipients under tacrolimus. Minors, patients with active skin or hair diseases, and patients with scalp hair shorter than 4 cm were excluded from participation. Scalp hair was collected from the posterior vertex of patients, cut into segments, and analyzed for tacrolimus by LC-MS/MS. Patients filled out a questionnaire on hair treatments and washing habits. In parallel, tacrolimus trough levels were measured in whole blood and correlated with hair tacrolimus concentrations.ResultsIn total, 39 consenting KT recipients were included, and hair samples were collected at 53 visits. Tacrolimus was detected in 98% of hair samples from patients exposed to the drug. Tacrolimus hair levels and whole blood trough levels were correlated with a beta coefficient of 0.42 (95% CI: −0.22–1.1, p = n.s.). Age and dark hair affected hair tacrolimus measurements, while different tacrolimus formulations (immediate release vs. extended release), hair washes, and permanent coloring did not. Longitudinal measurements in a subgroup of patients indicate that long-term measurement of hair tacrolimus levels is feasible.ConclusionMeasuring tacrolimus in hair is a potentially reliable method to monitor drug exposure in KT patients. Rapid wash-in effects and consistent concentrations over time indicate that tacrolimus is incorporated into the hair matrix, allowing temporal resolution in the analysis of recent exposure and exposure history. This method provides a simple and low-risk alternative to regular blood sampling, sparing patients from frequent hospital visits through the self-collection of hair samples

Entanglement of single-photons and chiral phonons in atomically thin WSe2_2

Quantum entanglement is a fundamental phenomenon which, on the one hand, reveals deep connections between quantum mechanics, gravity and the space-time; on the other hand, has practical applications as a key resource in quantum information processing. While it is routinely achieved in photon-atom ensembles, entanglement involving the solid-state or macroscopic objects remains challenging albeit promising for both fundamental physics and technological applications. Here, we report entanglement between collective, chiral vibrations in two-dimensional (2D) WSe$_2$ host --- chiral phonons (CPs) --- and single-photons emitted from quantum dots (QDs) present in it. CPs which carry angular momentum were recently observed in WSe$_2$ and are a distinguishing feature of the underlying honeycomb lattice. The entanglement results from a "which-way" scattering process, involving an optical excitation in a QD and doubly-degenerate CPs, which takes place via two indistinguishable paths. Our unveiling of entanglement involving a macroscopic, collective excitation together with strong interaction between CPs and QDs in 2D materials opens up ways for phonon-driven entanglement of QDs and engineering chiral or non-reciprocal interactions at the single-photon level