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Federal abortion protection reversals have increased the importance of understanding and addressing regional disparities in clinical abortion training. We surveyed Medical Students for Choice leaders in July 2022 about abortion training and analyzed results by state abortion laws. Of 100 survey respondents, 50 % reported institutional access to abortion training (17.5 % in restrictive states; 71.2 % in permissive states; χ 2  = 25.9, p < 0.00001) and 46 % indicated that they or a peer had attended a visiting student elective (VSE) covering abortion care (47.5 % in restricted states; 51.9 % in permissive states). Availability of clinical abortion training varies geographically by state abortion laws. VSEs may be underutilized., (Copyright © 2024. Published by Elsevier B.V.)

Background: Weight stigma among healthcare professionals is associated with negative health impacts on patients, yet there are few effective strategies to combat weight stigma among health professional learners. The Body Advocacy Movement-Health (BAM-Health) is a novel group-based, peer-led stigma reduction intervention for health professional students that targets weight stigma across intrapersonal, interpersonal, and structural levels. The present study (1) assesses short-term impacts of BAM-Health participation on intrapersonal and interpersonal weight bias compared to an informational brochure control condition and (2) explores the feasibility and acceptability of BAM-Health among a sample of health professional students., Methods: Sixty-seven health professional students participated in BAM-Health (n = 34) or received an informational brochure about weight stigma (n = 33). Participants completed validated self-report surveys assessing internalized weight/ appearance concerns and interpersonal weight stigma prior to their assigned intervention (baseline), immediately following intervention (post-intervention), and four weeks after intervention (follow-up). Baseline to post-intervention and baseline to follow-up effect sizes on each measure were calculated. At post-intervention, participants completed feedback surveys for thematic assessment., Results: BAM-Health participation had a large baseline to post-intervention effect on internalized weight/ appearance concerns that diminished slightly at follow-up (Cohen's d = -0.88; d = -0.62). Receipt of the informational brochure had a small effect on internalized weight/ appearance concerns (d = -0.27); however, these changes were not sustained at follow-up (d = 0.04). BAM-Health participation resulted in reductions in interpersonal obesity stigma and anti-fatness with small effect sizes (d = -0.32; d = -0.31). The effect on obesity stigma was slightly amplified at follow-up (d = -0.43); however, decreases in anti-fatness were not sustained (d = -0.13). The brochure condition failed to demonstrate effects on anti-fatness (d = 0.13, d = 0.14) or obesity stigma (d = -0.12; d = -0.12) at either time point. Between-session attrition rates of 4.5%, favorable quantitative ratings on post-session acceptability surveys, and free responses demonstrating appreciation of the virtual group environment and session activities reflect feasibility and acceptability of BAM-Health., Conclusions: BAM-Health is a novel peer-led intervention that aims to reduce weight stigma among health professional students. BAM-Health met feasibility benchmarks and received positive feedback from participants, demonstrating acceptability and indicating interest among health professional students in analyzing and reducing weight stigma in their personal lives and careers. The intervention led to promising decreases in internalized and interpersonal weight stigma at post-intervention, some of which were sustained at follow-up. However, lack of effect on internalized weight/ appearance concerns measures may indicate that BAM-Health participants are more likely to reject weight stigma directed toward others following intervention, while maintaining thin ideals for themselves. Further investigation of BAM-Health with a larger sample and continued program development is warranted., (© 2024. The Author(s).)

Oscillators exhibiting an Andronov-Hopf bifurcation are candidates to mimic the functionality of the cochlea, since the transfer response of these oscillators is compressive and frequency selective. The former implies that small stimuli are amplified and strong stimuli are attenuated, while the latter means that the oscillator only reacts in a (small) frequency band. However, this implies that many oscillators are needed to cover a relevant frequency band. By introducing the notion of tunable characteristic frequencies, i.e., the characteristic frequency can be adjusted by a controllable input, the number of oscillators can be eventually reduced. Subsequently, the tunability enhancement of coupled oscillators is investigated by analyzing the local dynamics of a network of oscillators. For this, necessary conditions for the emergence of Andronov-Hopf bifurcations are determined for networks consisting of two groups, i.e., a group is a network of identical oscillators. By choosing the eigenvalues of the product of the cross-coupling matrix as bifurcation parameters and exploiting the structure of the transfer matrix of this network, the critical points and, thus, the characteristic frequency at this point can be derived. Tunability of the characteristic frequency is then enabled by controlling the asymmetry between the groups of oscillators., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND) license (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Adaptive sampling and situational awareness are key features of modern autonomous underwater vehicles (AUVs) since data quality can be improved while operation time and cost can be reduced. An example for adaptive sampling in the marine environmental context is thermocline detection and tracking. The thermocline as horizontal ocean layer separates warm and cold water and is a key feature in many marine disciplines. For example, it influences the distribution and exchange of nutrients and is a habitat for many organisms. In this paper we use an unscented Kalman Filter (UKF) based extremum seeking control (ESC) to find and follow ocean layers such as the thermocline. Computer simulations and real-world tests show that the method is able to find and track non-trivial real-world ocean layers with sensors subject to hysteresis and delay effects., (© 2024. The Author(s).)

During the transition from liquid to solid, the thermal conductivity coefficient λ of concrete decreases. Although λ of hardened concrete is well investigated, there is limited research on the transition from liquid to solid and how it depends on hydration. Currently, only simplified qualitative approaches exist for the liquid state and the transient process. An experimental method is not available. For this purpose, a test rig is designed to experimentally capture the evolution of λ for fine-grain concretes during transition. The performance of the test setup is evaluated on a characteristic high-performance concrete (HPC). The results are compared to theoretical predictions from the literature. The developed test rig is mapped in a digital twin to investigate extended boundary conditions, such as different heat sources and temperatures of the experimental setup. It allows the experiment to be repeated and optimized for different setups with little effort. The test principle is as follows: A liquid concrete sample is heated through a controlled external source, while the transient temperature distribution over the height is measured with a fiber optic sensor. The thermal conductivity is derived from the heat flux induced and the temperature distribution over an evaluation length. Experiments show that λ in the liquid state is approximately 1.4 times greater than in the solid state and exponentially decreases for the transient process. Numerical results on the digital twin indicate that the robustness of the results increases with the temperature of the heat source. Moreover, the derivation in λ turns out to be strongly dependent on the evaluation length. A length of three times the maximum grain diameter is recommended.

Homeostasis comprises one of the main features of living organisms that enables their robust functioning by adapting to environmental changes. In particular, thermoregulation, as an instance of homeostatic behavior, allows mammals to maintain stable internal temperature with tightly controlled self-regulation independent of external temperatures. This is made by a proper reaction of the thermoeffectors (like skin blood vessels, brown adipose tissue (BAT), etc.) on a wide range of temperature perturbations that reflect themselves in the thermosensitive neurons' activity. This activity is being delivered to the respective actuation points and translated into thermoeffectors' actions, which bring the temperature of the organism to the desired level, called a set-point. However, it is still an open question whether these mechanisms can be implemented in an analog electronic device: both on a system theoretical and a hardware level. In this paper, we transfer this control loop into a real electric circuit by designing an analog electronic device for temperature regulation that works following bio-inspired principles. In particular, we construct a simplified single-effector regulation system and show how spiking trains of thermosensitive artificial neurons can be processed to realize an efficient feedback mechanism for the stabilization of the a priori unknown but system-inherent set-point. We also demonstrate that particular values of the set-point and its stability properties result from the interplay between the feedback control gain and activity patterns of thermosensitive artificial neurons, for which, on the one hand, the neuronal interconnections are generally not necessary. On the other hand, we show that such connections can be beneficial for the set-point regulation and hypothesize that the synaptic plasticity in real thermosensitive neuronal ensembles can play a role of an additional control layer empowering the robustness of thermoregulation. The electronic realization of temperature regulation proposed in this paper might be of interest for neuromorphic circuits which are bioinspired by taking the basal principle of homeostasis on board. In this way, a fundamental building block of life would be transferred to electronics and become a milestone for the future of neuromorphic engineering., (© 2023. The Author(s).)

Oscillator networks rapidly become one of the promising vehicles for energy-efficient computing due to their intrinsic parallelism of execution. The criticality property of the oscillator-based networks is regarded to be essential for performing complex tasks. There are numerous bio-inspired synaptic and structural plasticity mechanisms available, especially for spiking neural networks, which can drive the network towards the criticality. However, there is no solid connection between these self-adaption mechanisms and the task performance, and it is not clear how and why particular self-adaptation mechanisms contribute to the solution of the task, although their relation to criticality is understood. Here we propose an evolutionary approach for the structural plasticity that relies solely on the task performance and does not contain any task-independent adaptation mechanisms, which usually contribute towards the criticality of the network. As a driver for the structural plasticity, we use a direct binary search guided by the performance of the classification task that can be interpreted as an interaction of the network with the environment. Remarkably, such interaction with the environment brings the network to criticality, although this property was not a part of the objectives of the employed structural plasticity mechanism. This observation confirms a duality of criticality and task performance, and legitimizes internal activity-dependent plasticity mechanisms from the viewpoint of evolution as mechanisms contributing to the task performance, but following the dual route. Finally, we analyze the trained network against task-independent information-theoretic measures and identify the interconnection graph's entropy to be an essential ingredient for the classification task performance and network's criticality., (© 2022. The Author(s).)

In hematopoietic cell transplantation (HCT), permissive HLA-DPB1 mismatches between patients and their unrelated donors are associated with improved outcomes compared with nonpermissive mismatches, but the underlying mechanism is incompletely understood. Here, we used mass spectrometry, T-cell receptor-β (TCRβ) deep sequencing, and cellular in vitro models of alloreactivity to interrogate the HLA-DP immunopeptidome and its role in alloreactive T-cell responses. We find that permissive HLA-DPB1 mismatches display significantly higher peptide repertoire overlaps compared with their nonpermissive counterparts, resulting in lower frequency and diversity of alloreactive TCRβ clonotypes in healthy individuals and transplanted patients. Permissiveness can be reversed by the absence of the peptide editor HLA-DM or the presence of its antagonist, HLA-DO, through significant broadening of the peptide repertoire. Our data establish the degree of immunopeptidome divergence between donor and recipient as the mechanistic basis for the clinically relevant permissive HLA-DPB1 mismatches in HCT and show that permissiveness is dependent on HLA-DM-mediated peptide editing. Its key role for harnessing T-cell alloreactivity to HLA-DP highlights HLA-DM as a potential novel target for cellular and immunotherapy of leukemia., (© 2021 by The American Society of Hematology.)

In this paper a nonlinear filtering algorithm for count time series is developed that takes the non-negativity of the data into account and preserves positive definiteness of the covariance matrices of the model. For this purpose, a recently proposed variant of Kalman Filtering based on Singular Value Decomposition is incorporated into Iterative Extended Kalman Filtering, in order to estimate the states of a nonlinear state space model. The resulting algorithm is applied to the evaluation and design of therapies for patients suffering from Myoclonic Astatic Epilepsy, employing time series of daily seizure rate. The analysis provides a decision whether for a specific patient a particular anti-epileptic drug is increasing or reducing the seizure rate. Through a simulation study the proposed algorithm is validated. Additionally, for clinical data results obtained by the proposed algorithm are compared with the results from a Cox-Stuart trend test as well as with the visual assessment of experienced pediatric epileptologists.

HLA expression levels have been suggested to be genetically controlled by single nucleotide polymorphisms (SNP) in the untranslated regions (UTR), and expression variants have been associated with the outcome of chronic viral infection and hematopoietic stem cell transplantation (HSCT). In particular, the 3'UTR rs9277534-G/A SNP in HLA-DPB1 has been associated with graft-versus-host-disease after HSCT (Expression model); however its relevance in different immune cells and its mode of action have not been systematically addressed. In addition, there is a strong though not complete overlap between the rs9277534-G/A SNP and structural HLA-DPB1 T cell epitope (TCE) groups which have also been associated with HSCT outcome (TCE Structural model). Here we confirm and extend previous findings of significantly higher HLA-DPB1 expression in B cell lines, unstimulated primary B cells, and monocytes homozygous for rs9277534-G compared to those homozygous for rs9277534-A. However, these differences were abrogated by interferon-γ stimulation or differentiation into dendritic cells. We identify at least seven 3'UTR rs9277534-G/A haplotypes differing by a total of 37 SNP, also characterized by linkage to length variants of a short tandem repeat (STR) in intron 2 and TCE group assignment. 3'UTR mapping did not show any significant differences in post-transcriptional regulation assessed by luciferase assays between two representative rs9277534-G/A haplotypes for any of eight overlapping fragments. Moreover, no evidence for alternative splicing associated with the intron 2 STR was obtained by RT-PCR. In an exemplary cohort of 379 HLA-DPB1 mismatched donor-recipient pairs, risk prediction by the Expression model and the Structural TCE model was 36.7% concordant, with the majority of discordances due to non-applicability of the Expression model. HLA-DPB1 from different TCE groups expressed in the absence of the 3'UTR at similar levels by transfected HeLa cells elicited significantly different mean alloreactive CD4+ T-cell responses, as assessed by CD137 upregulation assays in 178 independent cultures. Taken together, our data provide new insights into the cell type-specific and mechanistic basis of the association between the rs9277534-G/A SNP and HLA-DPB1 expression, and show that, despite partial overlap between both models in HSCT risk-prediction, differential alloreactivity determined by the TCE structural model occurs independently from HLA-DPB1 differential expression.

This paper proposes an objective methodology for the analysis of epileptic seizure count time series by developing a non-linear state space model. An iterative extended Kalman filter (IEKF) is employed for the estimation of the states of the non-linear state space model. In order to improve convergence of the IEKF, the recently proposed Levenberg-Marquardt variant of the IEKF is explored. As external inputs time-dependent dosages of several simultaneously administered anticonvulsants are included. The aim of the analysis is to decide whether each anticonvulsant decreases or increases the number of seizures per day. The performance of the analysis is analyzed for simulated data, as well as for real data from a patient suffering from myoclonic-astatic epilepsy.

T cell alloreactivity is mediated by a self-human leukocyte antigen (HLA)-restricted T cell receptor (TCR) repertoire able to recognize both structurally similar and dissimilar allogeneic HLA molecules (i.e., differing by a single or several amino acids in their peptide-binding groove). We hypothesized that thymic selection on self-HLA molecules could have an indirect impact on the size and diversity of the alloreactive response. To test this possibility, we used TCR Vβ immunophenotyping and immunosequencing technology in a model of alloreactivity between self-HLA selected T cells and allogeneic HLA-DPB1 (DPB1) differing from self-DPB1*04:02 by a single (DPB1*02:01) or several (DPB1*09:01) amino acids in the peptide-binding groove. CD4+ T cells from three different self-DPB1*04:01,*04:02 individuals were stimulated with HeLa cells stably transduced with the relevant peptide processing machinery, co-stimulatory molecules, and HLA-DP. Flow cytometric quantification of the DPB1-specific T cell response measured as upregulation of the activation marker CD137 revealed significantly lower levels of alloreactivity against DPB1*02:01 compared with DPB1*09:01 (mean CD4+CD137+ frequency 35.2 ± 9.9 vs. 61.5 ± 7.7%, respectively, p  < 0.0001). These quantitative differences were, however, not reflected by differences in the breadth of the alloreactive response at the Vβ level, with both alloantigens eliciting specific responses from all TCR-Vβ specificities tested by flow cytometry, albeit with higher levels of reactivity from most Vβ specificities against DPB1*09:01. In line with these observations, TCRB -CDR3 immunosequencing showed no significant differences in mean clonality of sorted CD137+CD4+ cells alloreactive against DPB1*02:01 or DPB1*09:01 [0.39 (0.36-0.45) and 0.39 (0.30-0.46), respectively], or in the cumulative frequencies of the 10 most frequent responding clones (55-67 and 58-62%, respectively). Most of the clones alloreactive against DPB1*02:01 (68.3%) or DPB1*09:01 (75.3%) were characterized by low-abundance (i.e., they were not appreciable among the pre-culture T cells). Interestingly, however, their cumulative frequency was lower against DPB1*02:01 compared with DPB1*09:01 (mean cumulative frequency 35.3 vs. 50.6%, respectively). Our data show that, despite lower levels of alloreactivity, a similar clonal diversity can be elicited by structurally similar compared with structurally dissimilar HLA-DPB1 alloantigens and demonstrate the power of TCRB immunosequencing in unraveling subtle qualitative changes not appreciable by conventional methods.

The resolving power and relative efficiency of two off-axis reflection zone plates (RZPs) in the soft X-ray range between 1 nm and 5 nm were investigated. RZPs focus only a very narrow bandwidth around the design wavelength. By misaligning the RZP, the focused wavelength can be tuned through a much wider spectral range. Using a laser-produced plasma source, we demonstrate that a single RZP can be efficiently used for spectroscopy at arbitrary wavelengths in the investigated soft X-ray range.

This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53.1%) compared to primary tumors (37.5%) and distant metastases (21.4%) ( p = 0.0183 and p = 0.0005). The discordant rate was significantly higher in lymph node metastases/primary tumor pairs (74.6%) than in distant metastases/primary tumor pairs (52.4%) or lymph node metastases/distant metastases pairs (51.6%) ( p = 0.0113 and p = 0.0261) with more gain (86.7%) than loss (61.1%) of microsatellite instability in the discordant lymph node metastases ( p = 0.0024). Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years ( p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases ( p = 0.0418), and was associated with TP53 wild-type status of primary tumors ( p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations. In conclusion, mitochondrial microsatellite instability and its association with selected clinical and molecular markers are discordant in primary and metastatic colorectal cancer, which could have importance for surveillance and therapeutic strategies.

Aims: Failure and side effects of combined cytotoxic therapy are challenges in the treatment of metastatic colorectal cancer (CRC). DPYD gene variations can potentially predict toxicity to 5-fluorouracil (FU)-based therapy and KRAS-, NRAS-, BRAF-, PIK3CA-wild type status is a known prerequisite for epidermal growth factor receptor (EGFR) inhibitor therapy. This study was performed to search for a possible link between these therapeutic markers., Methods: The DPYD gene variations c.496A>G, c.1679T>G, c.2846A>T and KRAS/NRAS/BRAF/PIK3CA mutational status were determined in non-neoplastic, primary CRC and metastatic CRC tissue from 115 patients., Results: The polymorphism c.496A>G was the DPYD gene variant with the highest detection rate (12.9%), occurred predominantly in females (86.7%, p=0.0044) and was exclusively seen in KRAS wild type primary CRC (15/65 (23.1%) vs 0/51 (0%) in KRAS-mutated primary CRC, respectively, p=0.0001)., Conclusions: This genetic profile could define a patient group requiring alternative combined therapeutic approaches. Global testing of large patient cohorts is necessary to prove this concept., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The number of citations that papers receive has become significant in measuring researchers' scientific productivity, and such measurements are important when one seeks career opportunities and research funding. Skewed citation practices can thus have profound effects on academic careers. We investigated (i) how frequently authors misinterpret original information and (ii) how frequently authors inappropriately cite reviews instead of the articles upon which the reviews are based. To reach this aim, we carried a survey of ecology journals indexed in the Web of Science and assessed the appropriateness of citations of review papers. Reviews were significantly more often cited than regular articles. In addition, 22% of citations were inaccurate, and another 15% unfairly gave credit to the review authors for other scientists' ideas. These practices should be stopped, mainly through more open discussion among mentors, researchers and students.

This study investigates two-dimensional wave propagation in an elastic half-space with quadratic nonlinearity. The problem is formulated as a hyperbolic system of conservation laws, which is solved numerically using a semi-discrete central scheme. These numerical results are then analyzed in the frequency domain to interpret the nonlinear effects, specifically the excitation of higher-order harmonics. To quantify and compare the nonlinearity of different materials, a new parameter is introduced, which is similar to the acoustic nonlinearity parameter beta for one-dimensional longitudinal waves. By using this new parameter, it is found that the nonlinear effects of a material depend on the point of observation in the half-space, both the angle and the distance to the excitation source. Furthermore it is illustrated that the third-order elastic constants have a linear effect on the acoustic nonlinearity of a material.

Objective: To evaluate bone metabolism in patients with ankylosing spondylitis (AS) and test the hypothesis that osteoprotegerin (OPG) serum concentrations are correlated with the severity of bone loss as assessed by bone mineral density (BMD) and biochemical markers of bone turnover. Osteoporosis occurs frequently in patients with AS and OPG represents a soluble decoy receptor that neutralizes receptor activator of nuclear factor-kB ligand (RANKL), an essential cytokine for osteoclast function., Methods: Clinical data, radiographs of the spine, BMD of lumbar spine and the femur, biochemical markers of bone turnover, and serum levels of OPG were evaluated in 264 patients with AS (72% men) and 240 age-matched healthy controls (76% men)., Results: OPG serum levels were significantly lower in patients with AS compared to controls (1.84 +/- 1.15 vs 3.54 +/- 2.18 pmol/l, p < 0.001), and in contrast to controls, were not positively correlated with age. In addition, BMD of the hip and the femoral neck were significantly lower in patients with AS than in controls. There were positive correlations in patients with AS between BMD of the femoral neck and free testosterone serum levels in men and free estradiol serum levels in women, respectively. Patients with AS and osteoporosis had higher biochemical markers of bone resorption and inflammatory activity., Conclusion: Bone loss in patients with AS is associated with low sex steroid hormone serum levels, high biochemical markers of bone resorption and inflammatory activity, low OPG serum levels, and lack of compensatory age-related increase of OPG serum levels.

Hypothermia is a dangerous situation. It is defined by a core temperature of less than 35 degrees C. Aggressive rewarming is used if it is lower than 30 degrees C, comprising extracorporeal therapies. A case of a 63 year old lady is reported whose temperature was 21.8 degrees C, circulation was unstable, respiratory insufficiency prevailed and severe neurological dysfunction. Serum potassium was 2.9 mmol/l and pH corrected for temperature 7.61. The patient was rewarmed by hemofiltration (HF) over 6 hours with substitution of 18 l of a solution containing a concentration of potassium of 5 mmol/l. Though potassium levels declined initially and than slowly normalized in 9 hours there were no arrhythmias documented. The ECG showed prolongation of the PQ-, QRS-, and especially the QT-times. All clinical and neurological sequelae had disappeared after four days. HF thus seems to be a safe method of rewarming in very severe hypothermia.