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This paper presents an open-access data set of reanalysed radar reflectivities and rainfall rates at sub-kilometre spatial and minute temporal scales. Variability at these scales is a blind spot for both operational rain gauge networks and operational radar networks. In the urban area of Hamburg, precipitation measurements of a single-polarized X-band weather radar operating at high temporal (30 s), range (60 m), and azimuthal sampling (1°) resolutions are made available for a period of more than 8 years. We describe in detail the reanalysis of the raw radar data, outline the radar performance for the years 2013 to 2021, and discuss open issues and limitations of the data set. Several sources of radar-based errors were adjusted gradually, affecting the radar reflectivity and rainfall measurements, e.g. noise, alignment, non-meteorological echoes, radar calibration, and attenuation. The deployment of additional vertically pointing micro rain radars yields drop size distributions at the radar beam height, which effectively reduces errors concerning the radar calibration and attenuation correction and monitors the radar data quality. A statistical evaluation revealed that X-band radar reflectivities and rainfall rates are in very good agreement with the micro rain radar measurements. Moreover, the analyses of rainfall patterns shown for an event and accumulated rainfall of several months prove the quality of the data set. The provided radar reflectivities facilitate studies on attenuation correction and the derivation of further weather radar products, like an improved rainfall rate. The rainfall rates themselves can be used for studies on the spatial and temporal scales of precipitation and hydrological research, e.g. input data for high-resolution modelling, in an urban area. The radar reflectivities and rainfall rates are available at https://doi.org/10.26050/WDCC/LAWR_UHH_HHG_v2 (Burgemeister et al., 2024).

Introduction. Currently, for switching medium voltage circuits, vacuum circuit breakers are widely used, which have good arcing properties and high breaking capacity. One of the problems of creating the drive mechanism of such apparatus is the need to ensure the absence of contact welding when a through current of a short circuit of a given duration flows through them, which is achieved due to a certain amount of contact pressure. One of the problems arising in the design of circuit breakers is the need to fix the mechanism with a mechanical lock, which should hold the mechanism securely. This leads to significant specific mechanical loads, which in turn reduces the reliability of the circuit breaker. One way to solve these problems is to create a drive based on monostable or bistable electromagnetic actuators with highly coercive permanent magnets, which provide reliable fixation of the position of the contacts. Purpose. Investigation of the improved design of a bistable electromagnetic actuator based on permanent magnets of a medium voltage vacuum circuit breaker. Methods. Theoretical and experimental research and comparative analysis of existing and developed electromagnetic actuators. Conclusions. A new design of an electromagnetic bistable actuator with reduced overall dimensions is developed and tested. The electromechanical characteristics of the actuator correspond to the technical specifications, which is confirmed by both theoretical and experimental studies. The proposed actuator can be used as a drive mechanism for medium voltage vacuum circuit breakers.

General description of the research topic. A technique and an algorithm for calculating the thermal field of electromagnets operating in complex forced systems proposed by authors are considered. The widespread use of such devices in electromechanical switching devices allows not only to increase their speed but also significantly reduce the size, mass and energy losses, which indicates the relevance of this topic. The mathematical model of heating the windings of forced electromagnets proposed by the authors is a system of 1D differential equations of stationary heat transfer in a cylindrical coordinate system, supplemented by equations of electrical and magnetic circuits. This model allows to take into account the ripple of the currents in the windings and the losses in the magnetic core due to these ripples, contains certain signs of scientific novelty and represents the goal of the paper. The algorithm developed by the authors for calculating the thermal field of electromagnets operating in forced control systems is a complex iterative cycle. Its implementation is greatly simplified by using the Maple computing environment which allows to realize complicated and cumbersome mathematical transformations, automates the process of computations, and obtain results of numerical simulation in a convenient tabular and/or graphic form, which indicates the practical significance of this works. The results of comparison of computation results with experimental data presented in the paper indicate the adequacy of the model and algorithm proposed.

General description of the research topic. The authors propose a technique for calculating the dynamics of electromagnets operating in complex forced systems. Such forced electromagnets are widely used in electromechanical switching devices, in particular in vacuum contactors, to reduce their size, energy consumption and to increase speed, which indicates the relevance of this topic. A mathematical model of the dynamics of a forced electromagnetic system, which takes into account the peculiarities of behavior in transients of its individual elements – the mechanical system, the magnetic and electrical circuits, taking into account the interaction of the electromagnet with a control device when the apparatus is activated, contains certain signs of scientific novelty and is the purpose of the paper. The technique of calculating the dynamics of forced electromagnets uses the computing environment Maple. The calculation is based on a mathematical model, which is a system of nonlinear differential equations of the magnetic and electric circuits, supplemented by the equations of motion of the elements of a mechanical system. The use of the computing environment Maple, applied here to automatically perform the mathematical transformations, allows avoiding the complicated processes of choosing the numerical integration method, programming of complex and cumbersome equations and numerical integration procedures, to obtain results of calculations in convenient tabular and/or graphic form. This specifically indicates the practical significance of this work. The results of the comparison of calculations with previously published experimental data presented in the paper indicate the high efficiency of the proposed models and techniques.

Abstract Background Diarrhea is an important cause of morbidity and mortality worldwide. In Africa and Ghana in particular, it is estimated to contribute directly to 19 and 25% of pediatric mortality among children under 5 years, respectively. Methods Surveillance for hospitalized acute diarrheal illness was initiated in November 2010 through October 2012 in a referral hospital in southern Ghana, and a teaching hospital in northern Ghana. Consenting hospitalized patients who met a standardized case definition for acute diarrheal illness provided demographic and epidemiologic data. Stool samples were collected and tested by culture for bacteria and by enzyme immunoassays for a panel of viruses and parasites. Results A total of 429 patients were enrolled; 216 (50.3%) were under 5 years, and 221 (51.5%) were females. Stool samples were received from 153 patients. Culture isolates included Shigella sp., Salmonella spp., Plesiomonas sp. and Vibrio cholerae. Of 147 samples tested for viruses, 41 (27.9%) were positive for rotaviruses, 11 (7.5%) for astroviruses, 10 (6.8%) for noroviruses, and 8 (5.4%) for adenoviruses. Of 116 samples tested for parasitic infections; 4 (3.4%) were positive for Cryptosporidium sp. and 3 (2.6%) for Giardia lamblia. Of the enrolled patients, 78.8% had taken antibiotics prior to sample collection. Conclusions Diarrheal pathogens were identified across all ages, however, predominantly (81%) in the children under 5 years of age. This study also detected high antibiotic use which has the potential of increasing antibiotic resistance. The most common enteric pathogen detected (49.4%) was rotavirus.

We present a method to estimate spatially and temporally variable uncertainty of areal precipitation data. The aim of the method is to merge measurements from different sources, remote sensing and in situ, into a combined precipitation product and to provide an associated dynamic uncertainty estimate. This estimate should provide an accurate representation of uncertainty both in time and space, an adjustment to additional observations merged into the product through data assimilation, and flow dependency. Such a detailed uncertainty description is important for example to generate precipitation ensembles for probabilistic hydrological modelling or to specify accurate error covariances when using precipitation observations for data assimilation into numerical weather prediction models. The presented method uses the Local Ensemble Transform Kalman Filter and an ensemble nowcasting model. The model provides information about the precipitation displacement over time and is continuously updated by assimilation of observations. In this way, the precipitation product and its uncertainty estimate provided by the nowcasting ensemble evolve consistently in time and become flow-dependent. The method is evaluated in a proof of concept study focusing on weather radar data of four precipitation events. The study demonstrates that the dynamic areal uncertainty estimate outperforms a constant benchmark uncertainty value in all cases for one of the evaluated scores, and in half the number of cases for the other score. Thus, the flow dependency introduced by the coupling of data assimilation and nowcasting enables a more accurate spatial and temporal distribution of uncertainty. The mixed results achieved in the second score point out the importance of a good probabilistic nowcasting scheme for the performance of the method.

The theoretical framework of a novel approach for absolute radar calibration is presented and its potential analysed by means of synthetic data to lay out a solid basis for future practical application. The method presents the advantage of an absolute calibration with respect to the directly measured reflectivity, without needing a previously calibrated reference device. It requires a setup comprising three radars: two devices oriented towards each other, measuring reflectivity along the same horizontal beam and operating within a strongly attenuated frequency range (e.g. K or X band), and one vertical reflectivity and drop size distribution (DSD) profiler below this connecting line, which is to be calibrated. The absolute determination of the calibration factor is based on attenuation estimates. Using synthetic, smooth and geometrically idealised data, calibration is found to perform best using homogeneous precipitation events with rain rates high enough to ensure a distinct attenuation signal (reflectivity above ca. 30 dBZ). Furthermore, the choice of the interval width (in measuring range gates) around the vertically pointing radar, needed for attenuation estimation, is found to have an impact on the calibration results. Further analysis is done by means of synthetic data with realistic, inhomogeneous precipitation fields taken from measurements. A calibration factor is calculated for each considered case using the presented method. Based on the distribution of the calculated calibration factors, the most probable value is determined by estimating the mode of a fitted shifted logarithmic normal distribution function. After filtering the data set with respect to rain rate and inhomogeneity and choosing an appropriate length of the considered attenuation path, the estimated uncertainty of the calibration factor is of the order of 1 to 11 %, depending on the chosen interval width. Considering stability and accuracy of the method, an interval of eight range gates on both sides of the vertically pointing radar is most appropriate for calibration in the presented setup.

This publication intends to prove that a network of low-cost local area weather radars (LAWR) is a reliable and scientifically valuable complement to nationwide radar networks. A network of four LAWRs has been installed in northern Germany within the framework of the Precipitation and Attenuation Estimates from a High-Resolution Weather Radar Network (PATTERN) project observing precipitation with a temporal resolution of 30 s, a range resolution of 60 m and a sampling resolution of 1° in the azimuthal direction. The network covers an area of 60 km × 80 km. In this paper, algorithms used to obtain undisturbed precipitation fields from raw reflectivity data are described, and their performance is analysed. In order to correct operationally for background noise in reflectivity measurements, noise level estimates from the measured reflectivity field are combined with noise levels from the last 10 time steps. For detection of non-meteorological echoes, two different kinds of clutter algorithms are applied: single-radar algorithms and network-based algorithms. Besides well-established algorithms based on the texture of the logarithmic reflectivity field (TDBZ) or sign changes in the reflectivity gradient (SPIN), the advantage of the unique features of the high temporal and spatial resolution of the network is used for clutter detection. Overall, the network-based clutter algorithm works best with a detection rate of up to 70%, followed by the classic TDBZ filter using the texture of the logarithmic reflectivity field. A comparison of a reflectivity field from the PATTERN network with the product from a C-band radar operated by the German Meteorological Service indicates high spatial accordance of both systems in the geographical position of the rain event as well as reflectivity maxima. Long-term statistics from May to September 2013 prove very good accordance of the X-band radar of the network with C-band radar, but, especially at the border of precipitation events, higher-resolved X-band radar measurements provide more detailed information on precipitation structure because the 1 km range gate of C-band radars is only partially covered with rain. The standard deviation within a range gate of the C-band radar with a range resolution of 1 km is up to 3 dBZ at the borders of rain events. The probability of detection is at least 90%, the false alarm ratio less than 10% for both systems. Therefore, a network of high-resolution low-cost LAWRs can give valuable information on the small-scale structure of rain events in areas of special interest, e.g. urban regions, in addition to the nationwide radar networks.

The transient simulation of electro-quasistatic fields requires a formulation that takes both dielectric effects as well as nonlinear conductive effects into account. The successive solution of large linear systems of equations with similar or even identical system matrices has to be performed repeatedly if this formulation is discretized by the Finite-Element method and an Implicit-Runge-Kutta method, respectively. The solution processes can be accelerated by using subspace recycling techniques and subspace projection extrapolation techniques. Numerical results for three-dimensional high-voltage applications are presented and the efficiency of these techniques is shown.

Boundary Integral Equation formulations can be used to describe electromagnetic shielding problems. Yet, this approach frequently leads to integrals which contain a singularity and an oscillating part. Those integrals are difficult to handle when integrated naivly using standard integration techniques, and in some cases even a very high number of integration nodes will not lead to precise results. We present a method for the numerical quadrature of an integral with a logarithmic singularity and a cosine oscillator: a modified Filon-Lobatto quadrature for the oscillating parts and an integral transformation based on the error function for the singularity. Since this integral can be solved analytically, we are in a position to verify the results of our investigations, with a focus on precision and computation time.

A plane rectangular bar of conducting and permeable material is placed in an external low-frequency magnetic field. The shielding properties of this object are investigated by solving the given plane eddy current problem for the vector potential with the boundary integral equation method. The vector potential inside the rectangle is governed by Helmholtz' equation, which in our case is solved by separation. The solution is inserted into the remaining boundary integral equation for the exterior vector potential in the domain surrounding the bar. By expressing its logarithmic kernel as a Fourier integral the overall solution inside and outside the bar is calculated using analytical means only.

In magneto- and electroquasi-static time domain simulations with implicit time stepping schemes the iterative solvers applied to the large sparse (non-)linear systems of equations are observed to converge faster if more accurate start solutions are available. Different extrapolation techniques for such new time step solutions are compared in combination with the preconditioned conjugate gradient algorithm. Simple extrapolation schemes based on Taylor series expansion are used as well as schemes derived especially for multi-stage implicit Runge-Kutta time stepping methods. With several initial guesses available, a new subspace projection extrapolation technique is proven to produce an optimal initial value vector. Numerical tests show the resulting improvements in terms of computational efficiency for several test problems. In quasistatischen elektromagnetischen Zeitbereichsimulationen mit impliziten Zeitschrittverfahren zeigt sich, dass die iterativen Lösungsverfahren für die großen dünnbesetzten (nicht-)linearen Gleichungssysteme schneller konvergieren, wenn genauere Startlösungen vorgegeben werden. Verschiedene Extrapolationstechniken werden für jeweils neue Zeitschrittlösungen in Verbindung mit dem präkonditionierten Konjugierte Gradientenverfahren vorgestellt. Einfache Extrapolationsverfahren basierend auf Taylorreihenentwicklungen werden ebenso benutzt wie speziell für mehrstufige implizite Runge-Kutta-Verfahren entwickelte Verfahren. Sind verschiedene Startlösungen verfügbar, so erlaubt ein neues Unterraum-Projektion- Extrapolationsverfahren die Konstruktion eines optimalen neuen Startvektors. Numerische Tests zeigen die aus diesen Verfahren resultierenden Verbesserungen der numerischen Effizienz.

We know little about mammalian anemotaxis or wind sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we first tracked whisker tips in anesthetized rats under low (0.5 m/s) and high (1.5 m/s) airflow. Whisker tips showed increasing movement from low to high airflow conditions, with all whisker tips moving during high airflow. Low airflow conditions-most similar to naturally occurring wind stimuli-engaged whisker tips differentially. Most whiskers moved little, but the long supra-orbital (lSO) whisker showed maximal displacement, followed by the α, β, and A1 whiskers. The lSO whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter. Ex vivo extracted lSO whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography (micro-CT) revealed that the ring-wulst-the follicle structure receiving the most sensitive afferents-was more complete/closed in the lSO, and other wind-sensitive whiskers, than in non-wind-sensitive whiskers, suggesting specialization of the supra-orbital for omni-directional sensing. We localized and targeted the cortical supra-orbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supra-orbital whisker representation than in D/E-row barrel cortex. We assessed the behavioral significance of whiskers in an airflow-sensing paradigm. We observed that rats spontaneously turn towards airflow stimuli in complete darkness. Selective trimming of wind-responsive whiskers diminished airflow turning responses more than trimming of non-wind-responsive whiskers. Lidocaine injections targeted to supra-orbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supra-orbital whiskers act as wind antennae.

Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR+CD38+ EM CD4+ T cells, T regulatory-like cells, PD1+ EM CD8+ T cells, neutrophils, CD27+ TCRγδ cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4+ T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4+ T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD.

Background and aim: Acetaminophen (APAP) overdose is a major cause of acute liver injury, but the role of macrophages in the propagation of the hepatotoxicity is controversial. Early research revealed that macrophage inhibitors protect against APAP injury. However, later work demonstrated that macrophage ablation by acute pre-treatment with liposomal clodronate (LC) exacerbates the toxicity. To our surprise, during other studies, we observed that pre-treatment twice with LC seemed to protect against APAP hepatotoxicity, in contrast to acute pre-treatment. The aim of this study was to confirm that observation and to explore the mechanisms. Methods: We treated mice with empty liposomes (LE) or LC twice per week for 1 week before APAP overdose and collected blood and liver tissue at 0, 2, and 6 h post-APAP. We then measured liver injury (serum alanine aminotransferase activity, histology), APAP bioactivation (total glutathione, APAP-protein adducts), oxidative stress (oxidized glutathione (GSSG)), glutamate-cysteine ligase subunit c (Gclc) mRNA, and nuclear factor erythroid 2-related factor (Nrf2) immunofluorescence. We also confirmed the ablation of macrophages by F4/80 immunohistochemistry. Results: Pre-treatment twice with LC dramatically reduced F4/80 staining, protected against liver injury, and reduced oxidative stress at 6 h post-APAP, without affecting APAP bioactivation. Importantly, Gclc mRNA was higher in the LC group at 0 h and total glutathione was higher at 2 h, indicating accelerated glutathione re-synthesis after APAP overdose due to greater basal glutamate-cysteine ligase. Oxidative stress was lower in the LC groups at both time points. Finally, total Nrf2 immunofluorescence was higher in the LC group. Conclusions: We conclude that multiple pre-treatments with LC protect against APAP by accelerating glutathione re-synthesis through glutamate-cysteine ligase. Investigators using twice or possibly more LC pre-treatments to deplete macrophages, including peritoneal macrophages, should be aware of this possible confounder.

The article presents a study on the simulation of classroom variables by a computer program. A computer program is written to generate random samples of classroom variables having specified means and standard deviations, as well as particular intercorrelations. Parameter values for the program were obtained from a sample of actual elementary school classes. Random data generated by the program and representative values were found to be similar in appearance and magnitude to the source data. It was concluded that the computer opens up some interesting and apparently workable possibilities in the simulation of educational data.

INTRODUCTION The ability to negotiate around obstacles and change heading while walking is essential to household and community ambulation, as 35%–45% of all steps taken during the day involve turning (Glaister, 2007), with the number of turns increasing in more confined surroundings. For a turn trajectory to occur, time spent on the inner limb of the turn increases; concomitantly time spent on the outer limb decreases (Courtine, 2006). The opposite is true of stride length, where the inner-limb stride is shortened compared to the outer stride in order for the turn trajectory to occur. The movement adaptations required for turning may pose difficulties to someone with motor impairment. Difficulty with turning has been associated with increased fall risk and injury in the elderly (Robinovitch, 2013). Greater time and number of steps to perform a turn was found to be predictive of increased fall risk in elderly people with lower-limb amputation (LLA). The purpose of this study was to determine the differences between the temporal-spatial parameters of the prosthetic and intact limb in people with unilateral LLA during the 180-degree turn task of the Component Timed-Up-and-Go (cTUG) test (Clemens, 2017). Differences in temporal-spatial values were expected when the 180-degree turn is performed with a prosthetic inner limb (PIL) compared to an intact inner limb (IIL), and differences based on amputation level, at either the transtibial (TT) or transfemoral (TF) level, would exist. METHOD Subjects: Forty community-ambulating people with LLA, mean age of 47.9 ± 14.7 years, were recruited at a national amputee conference. Apparatus: Component timed-up-and-go (cTUG) test captured using a custom iPad application. Procedures: Subjects performed the cTUG twice (turning toward the prosthetic and sound limbs) on an instrumented walkway to capture temporal-spatial gait parameters. Data Analysis: Independent and paired t-tests were employed to examine differences in parameters between and within the groups based on level of amputation. RESULTS People with lower-limb amputation spent more time on their intact limb while turning than their prosthetic limb regardless of the position of the intact limb, and those with transfemoral amputation spent significantly more time over the intact limb than those with transtibial amputation. Additionally, subjects with transfemoral amputation performed the turn significantly faster when turning with an inner intact limb. DISCUSSION The present study demonstrates that community ambulating people with unilateral LLA perform a 180-degree turn using differing strategies, depending on whether the prosthetic limb or the intact limb is the inner limb of the turn, exposing adaptations prosthetic users employ during gait. These differences are amplified at more proximal amputation levels. CONCLUSION This is the first study to compare inner and outer limb parameters of turning in people with LLA, finding that prosthetic users turn differently than able-bodied people. This may put people with LLA at risk for overuse of their sound limb. [ABSTRACT FROM AUTHOR]

We previously demonstrated that endogenous phosphatidic acid (PA) promotes liver regeneration after acetaminophen (APAP) hepatotoxicity. Here, we hypothesized that exogenous PA is also beneficial. To test that, we treated mice with a toxic APAP dose at 0 h, followed by PA or vehicle (Veh) post-treatment. We then collected blood and liver at 6, 24, and 52 h. Post-treatment with PA 2 h after APAP protected against liver injury at 6 h, and the combination of PA and N-acetyl-l-cysteine (NAC) reduced injury more than NAC alone. Interestingly, PA did not affect canonical mechanisms of APAP toxicity. Instead, transcriptomics revealed that PA activated interleukin-6 (IL-6) signaling in the liver. Consistent with that, serum IL-6 and hepatic signal transducer and activator of transcription 3 (Stat3) phosphorylation increased in PA-treated mice. Furthermore, PA failed to protect against APAP in IL-6-deficient animals. Interestingly, IL-6 expression increased 18-fold in adipose tissue after PA, indicating that adipose is a source of PA-induced circulating IL-6. Surprisingly, however, exogenous PA did not alter regeneration, despite the importance of endogenous PA in liver repair, possibly due to its short half-life. These data demonstrate that exogenous PA is also beneficial in APAP toxicity and reinforce the protective effects of IL-6 in this model.

The onset of COVID-19 left people feeling unsettled, confused, and afraid of what tomorrow may hold. As university professors specializing in health communication, we too were left with these same feelings. As health communication scholars, we focus on issues surrounding illness, risk, crisis, care, health inequities, and wellness. COVID-19 is a health crisis, yes, but it has also changed the way we operate not only in higher education but in daily life. We begin this essay with an overview of COVID-19 and its impact on students, educators, and administrators. Then, we suggest four best practices to foster a community of care in the classroom during and beyond the COVID-19 pandemic.

Abstract Background Traditional healers are frequently exposed to hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) through the widespread practice of traditional “injections”, in which the healer performs dozens of subcutaneous incisions using a razor blade to rub herbs directly into bloodied tissue. An average healer in Agincourt, a rural northeastern sub-district in Mpumalanga province, South Africa, experiences approximately 1500 occupational blood exposures over the course of their lifetime. Healers in Agincourt have an HIV prevalence of 30% compared to 19% in the general population, and healers who report exposure to patient blood have an adjusted 2.4-fold higher odds of being HIV-positive than those with no exposure. Although research on appropriate PPE use has been well documented for allopathic care providers, little is known about the practices of traditional healers. Methods This qualitative study was conducted with 30 traditional healers who practice in the rural Bushbuckridge sub-district of Mpumalanga province, northeastern South Africa. We elicited traditional healer attitudes towards glove use during traditional treatments – including patient baths, injections, or other treatments that exposed healers to patient blood or open sores. Results While 90% of healers reported using latex gloves during some treatments, the majority do not use them regularly. Most employ a combination of gloves, plastic shopping bags, bread bags, paper, and sticks to prevent blood exposure. Healers reported plastic bags slipping or breaking during procedures, exposing them to patient blood. Only three healers consistently used gloves, regardless of the cost. Conclusions Inadequate PPE use and high HIV prevalence make traditional healers particularly susceptible to contracting HIV in rural South Africa. Despite positive attitudes, consistent glove use remains low due to financial constraints and glove availability. Addressing issues of accessibility and cost of gloves for traditional healers could have a significant impact on the adherence to PPE and, in turn, reduce new HIV infections among this high-risk group.

Kinship behavior in rodents has been documented in the laboratory setting but the neural mechanisms that mediate kinship behavior are not known. Here, the authors show that the lateral septum has a key role in organizing mammalian kinship behavior.

Introduction Public awareness of electronic nicotine delivery systems (ENDS) has increased over time, and the perception that ENDS offer a safer alternative to cigarettes may lead some pregnant women to use them to reduce cigarette smoking during pregnancy. No previous studies have used metabolite levels in hair to measure nicotine exposure for ENDS users during pregnancy. We aimed to measure and compare levels of nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in hair samples from pregnant women who were current ENDS users, current smokers, and current non-smokers. We also aimed to estimate the association between ENDS use/smoking and smallness for gestational age (SGA). Methods We used hair specimens from pregnant women who were dual users (ENDS and cigarettes), smokers, and non-smokers from a prospective cohort study to estimate exposure to nicotine, cotinine, and TSNAs. The exposure biomarkers and self-reports of smoking and ENDS use were used in log-binomial regression models to estimate risk ratios (RRs) for SGA among offspring. Results Nicotine concentrations for pregnant dual users were not significantly different from those for smokers (11.0 and 10.6 ng/mg hair, respectively; p=0.58). Similarly, levels of cotinine, and TSNAs for pregnant dual users were not lower than those for smokers. The RR for SGA was similar for dual users and smokers relative to nonsmokers, (RR=3.5, 95% CI: 0.8–14.8) and (RR=3.3, 95% CI: 0.9– 11.6), respectively. Using self-reports confirmed by hair nicotine, the RR values for dual ENDS users and smokers were 8.3 (95% CI: 1.0–69.1) and 7.3 (95% CI:1.0–59.0), respectively. Conclusions We did not observe lower levels of nicotine, cotinine, and TSNAs for current dual users compared to smokers during pregnancy. The risk of SGA for offspring of pregnant dual users was similar to that for offspring of pregnant smokers. Future studies are needed to further estimate the magnitude of the association between ENDS use and smallness for gestational age.

Introduction The 2016 US Surgeon General’s Report suggests that the use of electronic nicotine delivery systems (ENDS) is a fetal risk factor. However, no previous study has estimated their effect on adverse pregnancy outcomes. We assessed the prevalence of current ENDS use in pregnant women and explored the effect on birth weight and smallness-for-gestational-age (SGA), correcting for misclassification from nondisclosure of smoking status. Methods We conducted a cohort study with 248 pregnant women using questionnaire data and biomarkers (salivary cotinine, exhaled carbon monoxide, and hair nicotine). We evaluated the association between birth weight and the risk of SGA by applying multivariate linear and log-binomial regression to reproductive outcome data for 232 participants. Participants who did not disclose their smoking status were excluded from the referent group. Sensitivity analysis corrected for misclassification of smoking/ENDS use status. Results The prevalence of current ENDS use among pregnant women was 6.8% (95% CI: 4.4–10.2%); most of these (75%) were concurrent smokers. Using self-reports, the estimated risk ratio of SGA for ENDS users was nearly two times the risk in the unexposed (RR=1.9, 95% CI: 0.6–5.5), and over three times that for ENDS-only users versus the unexposed (RR=3.1, 95% CI: 0.8–11.7). Excluding from the referent group smokers who did not disclose their smoking status, the risk of SGA for ENDS-only use was 5 times the risk in the unexposed (RR=5.1, 95% CI: 1.1– 22.2), and almost four times for all types of ENDS users (RR=3.8, 95% CI: 1.3–11.2). SGA risk ratios for ENDS users, corrected for misclassification due to self-report, were 6.5–8.5 times that of the unexposed. Conclusions Our data suggest that ENDS use is associated with an increased risk of SGA.

The formation of Faraday waves in a liquid inside a cylindrical vessel under the influence of vertical vibration is studied. The stability thresholds and its mode decomposition are obtained using a linear stability analysis. The stability model is validated with a vibration experiment in a vertical vibration table. The Faraday instability threshold is found for accelerations ranging from 0.1 to 1.0 times the gravitational acceleration. The confinement effect by the vessel introduces cut-off the low frequency modes and the allowed frequencies are discretized. The resulting acceleration stability threshold is high at low frequencies and it is the lowest at medium frequencies, , where the discretization of the mode -momenta introduces low stability regions delimited by more stable frequency ranges. The relevance of these characteristics for the agitation of liquids will be discussed.

INTRODUCTION:In recent years, the traditional treatments for thrombotic diseases, heparin and warfarin, are increasingly being replaced by novel oral anticoagulants offering convenient dosing regimens, more predictable anticoagulant responses, and less frequent monitoring. However, these drugs can be contraindicated for some patients and, in particular, their bleeding liability remains high. METHODS:We have developed a new class of direct thrombin inhibitors (VE-DTIs) and have utilized kinetics, biochemical, and X-ray structural studies to characterize the mechanism of action and in vitro pharmacology of an exemplary compound from this class, Compound 1. RESULTS:We demonstrate that Compound 1, an exemplary VE-DTI, acts through reversible covalent inhibition. Compound 1 inhibits thrombin by transiently acylating the active site S195 with high potency and significant selectivity over other trypsin-like serine proteases. The compound inhibits the binding of a peptide substrate with both clot-bound and free thrombin with nanomolar potency. Compound 1 is a low micromolar inhibitor of thrombin activity against endogenous substrates such as fibrinogen and a nanomolar inhibitor of the activation of protein C and thrombin-activatable fibrinolysis inhibitor. In the thrombin generation assay, Compound 1 inhibits thrombin generation with low micromolar potency but does not increase the lag time for thrombin formation. In addition, Compound 1 showed weak inhibition of clotting in PT and aPTT assays consistent with its distinctive profile in the thrombin generation assay. CONCLUSION:Compound 1, while maintaining strong potency comparable to the current DTIs, has a distinct mechanism of action which produces a differentiating pharmacological profile. Acting through reversible covalent inhibition, these direct thrombin inhibitors could lead to new anticoagulants with better combined efficacy and bleeding profiles.

HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy.The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining.258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC.This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.

With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up.In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p

Introduction: In squamous cell carcinoma of the esophagus (ESCC), therapeutical options in 2nd-line treatment are scarce with immune checkpoint inhibition being the only approved one. Ramucirumab/paclitaxel is an approved 2nd-line treatment in metastatic esophagogastric adenocarcinoma. We assessed safety and efficacy of ramucirumab/paclitaxel for ESCC., Methods: This prospective, randomized, open-label, multicenter, phase II trial evaluated paclitaxel (80 mg/m2 days 1, 8, 15) plus ramucirumab (8 mg/kg days 1, 15) (investigational arm A) versus paclitaxel alone (80 mg/m2 days 1, 8, 15) (standard arm B), both q4w, in advanced/metastatic ESCC refractory or intolerant to fluoropyrimidine and platinum-based drugs. Primary endpoint was overall survival (OS) rate at 6 months., Results: From 3/2019 to 4/2021, 21/186 planned patients were included (arm A 11 patients; arm B 10 patients) in 9 German centers. Due to slow accrual, the study was terminated prematurely. OS at 6 months was 72.7% for ramucirumab/paclitaxel and 50.0% for paclitaxel. The study design did not allow statistical comparison of the arms. PFS (3.8 vs. 3.5 months), OS (12.1 vs. 9.2 months), ORR (18.2% vs. 20.0%) and DCR (54.5% vs. 60.0%) were comparable in both arms. Most common treatment-related adverse events (TRAEs) in arm A were leucopenia (54.5%), fatigue (27.3%), and peripheral sensory neuropathy (18.2%). 27.3% in arm A and 50.0% in arm B had TRAEs ≥ grade 3., Conclusion: Ramucirumab/paclitaxel shows an acceptable tolerability and numerically improved OS at 6 months. Due to the small number of patients, the current trial must be considered exploratory and more data are needed in this indication., (© 2024 S. Karger AG, Basel.)

Innovative analytical instruments and development of new methods has provided a better understanding of protein particle formation in biopharmaceuticals but have also challenged the ability to obtain reproducible and reliable measurements. The need for protein-like particle standards mimicking the irregular shape, translucent nature and near-to-neutral buoyancy of protein particles remained one of the hot topics in the field of particle detection and characterization in biopharmaceutical formulations. An innovative protein-like particle model has been developed using two photo polymerization (2PP) printing allowing to fabricate irregularly shaped particles with similar properties as protein particles at precise size of 50 µm and 150 µm, representative of subvisible particles and visible particles, respectively. A study was conducted to compare the morphological, physical, and optical properties of artificially generated protein particles, polystyrene spheres, ETFE, and SU-8 particle standards, along with newly developed protein-like model particles manufactured using 2PP printing. Our results suggest that 2PP printing can be used to produce protein-like particle standards that might facilitate harmonization and standardization of subvisible and visible protein particle characterization across laboratories and organizations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gene flow can have rapid effects on adaptation and is an important evolutionary tool available when undertaking biological conservation and restoration. This tool is underused partly because of the perceived risk of outbreeding depression and loss of mean fitness when different populations are crossed. In this article, we briefly review some theory and empirical findings on how genetic variation is distributed across species ranges, describe known patterns of gene flow in nature with respect to environmental gradients, and highlight the effects of gene flow on adaptation in small or stressed populations in challenging environments (e.g., at species range limits). We then present a case study involving crosses at varying spatial scales among mountain populations of a trigger plant (Stylidium armeria: Stylidiaceae) in the Australian Alps to highlight how some issues around gene flow effects can be evaluated. We found evidence of outbreeding depression in seed production at greater geographic distances. Nevertheless, we found no evidence of maladaptive gene flow effects in likelihood of germination, plant performance (size), and performance variance, suggesting that gene flow at all spatial scales produces offspring with high adaptive potential. This case study demonstrates a path to evaluating how increasing sources of gene flow in managed wild and restored populations could identify some offspring with high fitness that could bolster the ability of populations to adapt to future environmental changes. We suggest further ways in which managers and researchers can act to understand and consider adaptive gene flow in natural and conservation contexts under rapidly changing conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Evolutionary Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To evaluate the trends in the incidence of major limb amputations and the prevalence of Dutch prosthetic users at the national level in The Netherlands between 2012 and 2021 (during the COVID-19 pandemic). Local hospitals in The Netherlands reported a doubling of major lower limb amputations during COVID-19, information about a change in the incidence of major upper limb amputations was not reported. We could not confirm this remarkable increase in major lower limb amputations in our institution, nor did we observe a change in the incidence of major upper limb amputations. We hypothesize that the COVID-19 pandemic had no effect on the number of major limb amputations., Design: Observational retrospective study analyzing national open-access databases of health insurance claims., Setting: The Dutch national opensource database www.opendisdata.nl was used to retrieve the incidence of limb amputations in the period 2012-2021, stratified by the level of amputation and the cause of amputation. The results were verified using the www.gipdatabank.nl databank. This period included 4 intervals of nationwide COVID-19 lockdowns., Participants: 60,848 patients who underwent limb amputations at the upper or lower extremity in the Netherlands from 2012 to 2021 (N=60,848) were included in this study., Intervention: Not applicable., Main Outcome Measures: Upper- and lower-limb amputation and prosthetic use., Results: Data were retrieved for a total of 60,848 patients in the Netherlands, who underwent 68,180 amputations of the upper and lower extremities at any level from 2012 to 2021, including 22,095 major amputations of the lower extremities. The ongoing trend of stable numbers of major lower-limb amputations from 2012 to 2019 continued in 2020 and 2021. The verification of these data at the level of prosthetic users confirmed that the annual trends were unchanged., Conclusion: The reported increased numbers of major lower-limb amputations during the COVID-19 pandemic in the Netherlands could not be confirmed using nationwide epidemiologic data., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Optimal management of septic patients requires accurate assessment of both current severity status and prognosis. Since the 1990s, substantial advances have been made in the use of circulating biomarkers for such assessments. This summary of the session on "Biomarkers: can they really use guide our daily practice?" presented at the 2021 WEB-CONFERENCE OF THE EUROPEAN SHOCK SOCIETY, 6 November 2021. These biomarkers include ultrasensitive detection of bacteremia, circulating soluble urokina-type plasminogen activator receptor (suPAR), C-reactive protein (CRP) and ferritin and procalcitonin. In addition, the potential application of novel multiwavelength optical biosensor technology allows noninvasive monitoring of multiple metabolites that can be used to assess severity and prognosis in septic patients. The application these biomarkers and improved technologies provide the potential for improved personalized management of septic patients., Competing Interests: M.F. served as advisor for SOBI and Menarini and as both advisor and speaker for GSK. F.V. is cofounder and Chie Scientific Officer of ApoH-Technologies; He acknowledges ApoH-Technologies’ team as well as the European Commission for the European Projects: EDCTP “PANDORA-ID-NET” (grant no. RIA2016E-1609) and Horizon Europe “EPIC-Crown 2” (grant no. 101046084). The rest of the authors report no conflict of interests., (Copyright © 2023 by the Shock Society.)

Introduction: Non-Invasive Prenatal Screening (NIPS) is a useful screening method for common aneuploidies that can occur in pregnancies. It yields high sensitivities and specificities for the targeted conditions it tests for. Most commonly, these include Trisomies in chromosomes 21, 18, and 13, as well as aneuploidies in chromosomes X and Y. It does not, however, replace diagnostic testing. We review four cases seen by our institutions of patients who had NIPS performed with low-risk results and subsequently had fetuses affected with trisomy 18., Methods: All fetal samples were evaluated by level II anatomic ultrasound and tested on amniocytes or products of conception through karyotype or chromosomal microarray following low-risk NIPS., Results: None of the fetuses showed evidence of mosaicism and had features (both on ultrasound and postnatally) consistent with Trisomy 18. Postnatal fluorescence in situ hybridization performed on Formalin-Fixed Paraffin-Embedded tissue from 3 of the affected pregnancies' placentas identified mosaicism of trisomy 18., Discussion: We discuss the possible explanations for the discrepancy between NIPS results and fetal karyotype, including, but not limited to placental mosaicism, placental size, and limitations of NIPS as a screening test., (© 2022 John Wiley & Sons Ltd.)

Background: A diet high in parent's own milk (parental milk) is a lifesaving intervention for critically ill infants. Lactating parents whose infants are born with birth defects that require surgical repair (surgical infants) shortly after birth often struggle to initiate and maintain a milk supply that meets their infant's nutritional needs. Antenatal milk expression has been identified as a safe, feasible, and potentially effective strategy that promotes parents' direct chest/breastfeeding or milk expression (lactation) confidence and helps parents attain their lactation goals. Two cases are presented to illustrate the potential for using antenatal milk expression as a lactation support intervention for parents of surgical infants., Case Presentation: Cases were drawn from a pilot study exploring the feasibility of implementing antenatal milk expression among pregnant parents of surgical infants. Participants were healthy women recruited after 30 weeks of gestation who received a fetal diagnosis of a complex congenital heart defect. Despite variability in clinical course and length of stay, parental milk was provided for the duration of each infant's hospitalization. Participant perceptions of antenatal milk expression varied., Conclusion: More research is needed to evaluate the feasibility, efficacy, and parent or provider perceptions of antenatal milk expression as a lactation support intervention for parents of surgical infants., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy., Methods: Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models., Results: AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89-1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80-1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86-1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77-1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3-4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology., Conclusion: For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy., (© 2022. The Author(s).)

Epidermal Patterning Factor Like 9 (EPFL9), also known as STOMAGEN, is a cysteine-rich peptide that induces stomata formation in vascular plants, acting antagonistically to other epidermal patterning factors (EPF1, EPF2). In grapevine there are two EPFL9 genes, EPFL9-1 and EPFL9-2 sharing 82% identity at protein level in the mature functional C-terminal domain. In this study, CRISPR/Cas9 system was applied to functionally characterize VvEPFL9-1 in 'Sugraone', a highly transformable genotype. A set of plants, regenerated after gene transfer in embryogenic calli via Agrobacterium tumefaciens , were selected for evaluation. For many lines, the editing profile in the target site displayed a range of mutations mainly causing frameshift in the coding sequence or affecting the second cysteine residue. The analysis of stomata density revealed that in edited plants the number of stomata was significantly reduced compared to control, demonstrating for the first time the role of EPFL9 in a perennial fruit crop. Three edited lines were then assessed for growth, photosynthesis, stomatal conductance, and water use efficiency in experiments carried out at different environmental conditions. Intrinsic water-use efficiency was improved in edited lines compared to control, indicating possible advantages in reducing stomatal density under future environmental drier scenarios. Our results show the potential of manipulating stomatal density for optimizing grapevine adaptation under changing climate conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Clemens, Faralli, Lagreze, Bontempo, Piazza, Varotto, Malnoy, Oechel, Rizzoli and Dalla Costa.)

Introduction: Since January 2002, pre-deployment training of forward resuscitative and surgical units has taken place at the U.S. Army Trauma Training Center (ATTC) in Miami, FL. In June 2019, the 240th Forward Resuscitative Surgical Team (FRST) conducted the first pre-deployment Surgical Readiness Training Exercise (SURGRETE) in San Pedro Sula, Honduras, to allow the team to rehearse in a resource-constrained environment more similar to that expected on deployment. The purpose of this study is to describe and compare the pre-deployment training experiences of the 240th FRST during their SURGRETE in Honduras and ATTC rotation in Miami, FL., Materials and Methods: A descriptive analysis of prospectively collected data was performed for surgical cases, trauma resuscitations, and nonsurgical procedures by the 240th FRST over a 2-week SURGRETE in Honduras and 2-week ATTC rotation in Miami, FL. Items accomplished within the Individual Critical Task Lists (ICTLs) of key clinical providers on the team (general surgeon, orthopedic surgeon, emergency medicine physician, and Certified Registered Nurse Anesthetist) were identified and compared to those accomplished at the ATTC., Results: During the SURGRETE in Honduras, 64 surgical cases, 1 trauma resuscitation, 2 Advanced Cardiac Life Support codes, and 213 nonsurgical procedures were performed collectively by the team. During ATTC rotation, the team performed a combined total of 10 surgical cases, 6 trauma resuscitations, and 56 nonsurgical procedures. For each key clinical provider, more of their assigned ICTLs were conducted during the Honduras SURGRETE than during ATTC rotation. The ATTC, however, offered more cases of acute life-threatening trauma., Conclusion: Appropriately planned SURGRETEs can provide a concentrated case volume in a resource-constrained setting and challenge the team to consider definitive management algorithms. The cases performed may not necessarily reflect the type and acuity of operations performed in a deployed environment; however, they facilitate repetition of basic skills, team cohesion, and cross-training. The SURGRETE experience could be improved by locating a facility with a trauma-dominant patient population that allows increased autonomy of U.S. physicians., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Breast conservation surgery (BCS) is the treatment of choice for unifocal, early-stage breast cancer. The ability to offer BCS to a wider subset of patients, including those with multifocal/multicentric cancer as well as extensive ductal carcinoma in situ, has emerged over time, especially in those undergoing joint oncoplastic reconstruction and those treated with neoadjuvant therapy. However, localization techniques using multiple radioactive seeds for bracketing in this patient subset have not been validated., Materials and Methods: A single-institution retrospective review was conducted of all patients with breast cancer who underwent BCS, guided by multiple bracketed iodine I 125 radioactive seeds between January 2014 and April 2017., Results: Bracketing of breast cancer using 2 or more radioactive seeds was performed in 157 breasts in 156 patients. Negative margins were achieved in 124 of 157 (79%) breasts, including 33 cases (21%) that underwent targeted margin reexcision at the time of surgery after intraoperative, multidisciplinary margin assessment. Thirty-three cases (21%) resulted in close or positive margins, of which 11 (7%) and 10 (6.4%) underwent completion mastectomy or repeat lumpectomy, respectively. Twelve patients (7.6%) did not undergo reexcision. En bloc resection was successful in 134 of 157 (85.4%) lumpectomies. Eighty-nine percent of the procedures were coupled with oncoplastic reconstruction., Conclusion: Bracketing techniques using multiple radioactive seeds expands the indications for breast conservation therapy in patients who would have traditionally required mastectomy. Intraoperative margin assessment improves surgical and pathologic success. Larger defects created by multifocal resection are optimally managed in concert with oncoplastic reconstruction to minimize asymmetries and aesthetic defects., (Published by Elsevier Inc.)

Purpose: Patients with reciprocal balanced translocations (RBT) have a risk for recurrent pregnancy losses (RPL), affected child, and infertility. Currently, genetic counseling is based on karyotypes found among the products of conception (POC), although factors influencing the success of assisted reproductive technologies (ART) in RBT couples are not established., Methods: Cytogenetic results from 261 POC and offspring of the parents (113 women and 90 men) with RBT were evaluated. Chromosome segregation modes and number of euploid embryos were assessed in couples undergoing in vitro fertilization., Results: Patients with translocations involving an acrocentric chromosome have a higher risk of unbalanced gametes caused by a 3:1 segregation. Female RBT patients have a statistically higher risk of aneuploidy due to an interchromosomal effect. The rate of euploid embryos is low due to meiosis I malsegregation of RBT, meiosis II nondisjunction, additional whole chromosome or segmental aneusomies. RBT patients with RPL have a higher rate of miscarriage of euploid fetuses with RBT., Conclusion: Chromosome-specific factors, female gender, age, and history of RPL are the risk elements influencing pregnancy and in vitro fertilization success in RBT patients. Chromosomal microarray analysis of POC is necessary to provide an accurate and timely diagnosis for patients with adverse reproductive outcomes., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Background: Invasive lobular breast cancer (BC) is the second most common BC subtype. Prognostic parameters (tumor classification, lymph node status, histologic grade, Oncotype DX recurrence score [RS], progesterone receptor status, and Ki67 index) were retrospectively studied in a large, prospective clinical trial encompassing 2585 patients who had hormone receptor-positive early BC (the West German Study Group PlanB trial)., Methods: BCs were centrally reviewed and classified as lobular (n = 353; 14%) or nonlobular (n = 2232; 86%). The median follow-up was 60 months. Five-year disease-free survival (DFS) estimates were obtained using the Kaplan-Meier method. Prognostic parameters were evaluated using Cox proportional hazard models., Results: Lobular BC was associated with higher tumor classification, higher lymph node status, lower histologic grade, lower Ki67 index, and low or intermediate RS. The prevalence of high RS (RS range, 26-100) was 3-fold lower in patients who had lobular BC compared with those who had nonlobular BC (8% vs 24%; P < .001). However, 5-year DFS estimates for lobular and nonlobular BC were similar (92.1% and 92.3%, respectively; P = .673). In multivariate analyses, prognostic parameters for DFS in lobular BC included grade 3 (hazard ratio, 5.06; 95% CI, 1.91-13.39) and a pathologic lymph node status (pN) of pN3 (hazard ratio, 12.16; 95% CI, 3.87-38.24), but not RS. By contrast, prognostic parameters in nonlobular BC included grade 3 (hazard ratio, 1.65; 95% CI, 1.11-2.44), pN3 (hazard ratio, 3.68; 95% CI, 1.60-8.46), and high RS (hazard ratio, 2.49; 95% CI, 1.69-3.68)., Conclusions: Lobular BC is associated with low and intermediate RS, although 5-year DFS is similar to that of nonlobular BC. The effect of the RS in lobular BC appears to be distinct from that in nonlobular BC. For risk assessment, the RS needs to be complemented by clinicopathologic parameters for therapy decision making., (© 2020 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The vertebrate clade diverged into Chondrichthyes (sharks, rays, and chimeras) and Osteichthyes fishes (bony fishes) approximately 420 mya, with each group accumulating vast anatomical and physiological differences, including skin properties. The skin of Chondrichthyes fishes is covered in dermal denticles, whereas Osteichthyes fishes are covered in scales and are mucous rich. The divergence time among these two fish groups is hypothesized to result in predictable variation among symbionts. Here, using shotgun metagenomics, we test if patterns of diversity in the skin surface microbiome across the two fish clades match predictions made by phylosymbiosis theory. We hypothesize (1) the skin microbiome will be host and clade-specific, (2) evolutionary difference in elasmobranch and teleost will correspond with a concomitant increase in host-microbiome dissimilarity, and (3) the skin structure of the two groups will affect the taxonomic and functional composition of the microbiomes., Results: We show that the taxonomic and functional composition of the microbiomes is host-specific. Teleost fish had lower average microbiome within clade similarity compared to among clade comparison, but their composition is not different among clade in a null based model. Elasmobranch's average similarity within clade was not different than across clade and not different in a null based model of comparison. In the comparison of host distance with microbiome distance, we found that the taxonomic composition of the microbiome was related to host distance for the elasmobranchs, but not the teleost fishes. In comparison, the gene function composition was not related to the host-organism distance for elasmobranchs but was negatively correlated with host distance for teleost fishes., Conclusion: Our results show the patterns of phylosymbiosis are not consistent across both fish clades, with the elasmobranchs showing phylosymbiosis, while the teleost fish are not. The discrepancy may be linked to alternative processes underpinning microbiome assemblage, including possible historical host-microbiome evolution of the elasmobranchs and convergent evolution in the teleost which filter specific microbial groups. Our comparison of the microbiomes among fishes represents an investigation into the microbial relationships of the oldest divergence of extant vertebrate hosts and reveals that microbial relationships are not consistent across evolutionary timescales. Video abstract.

Background: The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii) whether the survival impact of TIL measurements varies according to different adjuvant systemic therapies., Methods: The WSG PlanB trial compared an anthracycline-free chemotherapy regimen (6x docetaxel/cyclophosphamide, TC) to an anthracycline-taxane sequence (4xEC followed by 4x docetaxel) in patients with intermediate-risk, HER2-negative early breast cancer (EBC). Patients with HR-positive HER2-negative EBC were further stratified to receive endocrine therapy alone vs. chemotherapy followed by endocrine therapy based on Recurrence Score results and nodal status. In this analysis, three independent observers quantified and categorized the presence of TILs among tumor samples from patients in PlanB. TIL measurements were correlated with clinical/pathological parameters and treatment outcome overall and according to the treatment arm., Results: Disease-free survival (DFS) rates were significantly better (p = .04) in HR-negative patients with high vs. intermediate TIL levels and were higher in low vs. intermediate TIL patients, however with borderline significance only (p = .06). There were no significant differences among TIL categories in HR+ patients. High RS categories, HR-negative status, and high KI67 were independently and significantly associated with high TIL categories. There was no significant impact of TIL category on DFS in patients treated by endocrine therapy only; however, in patients receiving chemotherapy, DFS in the intermediate TIL category was lower than that in the other categories., Conclusion: Although the presence of high TILs is associated with negative prognostic parameters such as high KI67 and HR-negative status among patients with HR-positive HER2-negative EBC, patients with high TILs show a favorable 5-year DFS in both HR-positive/HER2-negative and triple-negative breast cancer.