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We sought to assess the effect of postoperative renal failure (RF) on outcomes of acute type A aortic dissection (ATAAD) and identify predictors of chronic kidney disease (CKD) following ATAAD.

Introduction:Limited palmar fasciectomy (LPF) and collagenase injection (CI) are the most common procedures to manage symptoms of Dupuytren's Disease. This randomized controlled trial (RCT) aimed to directly compare patient outcomes 12 months following CI and LPF. Methods:Twenty-two patients with Dupuytren's Disease were randomized to either LPF or CI. The primary outcome was health state measured by the Michigan Hand Questionnaire. Secondary outcomes were health status (The Health Utility Index-3), function (The Unité Rhumatologique des Affections de la Main and The Southampton Dupuytren's Scoring Scheme), and range of motion (ROM) of treated digits. Measurements were collected at baseline and 1-, 3-, 6-, and 12-months post-procedure. Results:Thirteen patients were randomized to the LPF and eight patients to the CI group. Most patients (85.7%) were male; the average age of the sample was 65.3 years. No statistically significant difference in the MHQ (mean difference [MD]: −12.4 (95% confidence interval [CI]: −30.0, 5.2)), SDSS (.9 (−4.0, 5.8)), URAM (−.9 (−14.4, 12.6)) or HUI-3 (−.04, −.2, .2)) was found between groups 12-months post-operatively. There was no statistically significant difference in 12-month loss of extension between groups at the MCP (−16.9 (−35.4, 1.7) or PIP (−2.9 (−22.9, 17.1) joints. Three CI patients and 1 LPF patient developed a contracture in the same digit requiring surgery. Conclusion:Results should be interpreted with caution given the small sample size. Available data suggests both techniques are reasonable for managing Dupuytren's Disease. Considerations for future RCTs are provided.

Introduction:To recruit enough patients to achieve adequate statistical power in clinical research, investigators often rely on financial incentives. The use of these incentives, however, remains controversial as they may cause patients to overlook risks associated with research participation. This concern is amplified in the context of plastic surgery where aesthetic procedures are often more desirable and are not typically covered by public or private insurance plans. Despite this, the ethical debate regarding the use of incentives has largely been absent from plastic surgery journals; therefore, efforts to summarize the existing literature in the context of plastic surgery are necessary. Methods:A narrative review of the peer-reviewed published literature was performed to identify existing articles pertaining to financial incentives in plastic surgery-related health research. Results:While incentives have the potential to improve sample sizes and promote the recruitment of under-represented patient populations, undue inducement and biased recruitment are possible. At present, there exists a paucity of empirical evidence to substantiate this. Efforts should be taken by investigators and research ethics boards (REBs) to limit the potential negative impacts of monetary compensation. Investigators should place reasonable limits on the value of incentives as well as select models associated with lower risks of undue influence and enrollment bias. When financial remuneration is offered, additional care should be taken by investigators to ensure participants are adequately informed of the risks associated with research participation. Conclusion:Current best practice recommendations suggest that proposals submitted to REBs justify the incentives used. Information regarding incentives should also be included within study consent forms and communicated as part of the informed consent process.

Unmanned aerial vehicles (UAVs) are well-suited for various short-distance missions in urban environments. However, the path planner of such UAV is constantly challenged with the choice between avoiding obstacles horizontally or vertically. If the path planner relies on sensor information only, i.e. the path planner is a local planner, usually predefined manoeuvres or preferences are used to find a possible way. However, this method is stiff and inflexible. This work proposes a probabilistic decision-maker to set the control parameters of a classic local path planner during a flight mission. The decision-maker defines whether performing horizontal or vertical avoidance is preferable based on the probability of encountering a given number of obstacles. Here, the decision-maker considers predictions of possible future avoidance manoeuvres. It also defines an ideal flight altitude based on the probability of encountering obstacles. This work analyses the building height of all European capital cities and the probability of encountering obstacles at different altitudes to feed the decision-maker. We tested the feasibility of the proposed decision-maker with the 3DVFH*, a commonly used local path planner, in multiple simulations. The proposed probabilistic decision-maker allows the local path planner to reach the goal point significantly more often than the standard version of the 3DVFH*.

Unmanned Aerial Vehicles (UAV) constantly gain in versatility. However, more reliable path planning algorithms are required until full autonomous UAV operation is possible. This work investigates the algorithm 3DVFH* and analyses its dependency on its cost function weights in 2400 environments. The analysis shows that the 3DVFH* can find a suitable path in every environment. However, a particular type of environment requires a specific choice of cost function weights. For minimal failure, probability interdependencies between the weights of the cost function have to be considered. This dependency reduces the number of control parameters and simplifies the usage of the 3DVFH*. Weights for costs associated with vertical evasion (pitch cost) and vicinity to obstacles (obstacle cost) have the highest influence on the failure probability of the local path planner. Environments with mainly very tall buildings (like large American city centres) require a preference for horizontal avoidance manoeuvres (achieved with high pitch cost weights). In contrast, environments with medium-to-low buildings (like European city centres) benefit from vertical avoidance manoeuvres (achieved with low pitch cost weights). The cost of the vicinity to obstacles also plays an essential role and must be chosen adequately for the environment. Choosing these two weights ideal is sufficient to reduce the failure probability below 10%.

Corrosion of alloys in molten salts is commonly understood from thermodynamics: the higher the content of noble elements in the alloy, the more corrosion resistant the alloy is expected to be. Here, we present an example in the CrFeMnNi compositionally complex space that defies this conventional intuition. Machine learning-facilitated analysis of the extensive dataset reveals that molten salt corrosion in this system is primarily predicted by the Ni mobility within the alloy. This discovery was made possible using high-throughput manufacturing and testing of a set of 110 compositionally complex alloys within the CrFeMnNi element space prepared by additive manufacturing in situalloying processes and corrosion tested in standardized conditions of temperature and chlorine potential. A standardized, parametric dataset of this magnitude for corrosion in molten salts is a first of its kind. This dataset results in new insights into the corrosion mechanism of CrFeMnNi for clean energy-enabling technologies.

Medical training programs and health care systems collect ever-increasing amounts of educational and clinical data. These data are collected with the primary purpose of supporting either trainee learning or patient care. Well-established principles guide the secondary use of these data for program evaluation and quality improvement initiatives. More recently, however, these clinical and educational data are also increasingly being used to train artificial intelligence (AI) models. The implications of this relatively unique secondary use of data have not been well explored. These models can support the development of sophisticated AI products that can be commercialized. While these products have the potential to support and improve the educational system, there are challenges related to validity, patient and learner consent, and biased or discriminatory outputs. The authors consider the implications of developing AI models and products using educational and clinical data from learners, discuss the uses of these products within medical education, and outline considerations that should guide the appropriate use of data for this purpose. These issues are further explored by examining how they have been navigated in an educational collaborative.

Obstacle avoidance is critical for unmanned aerial vehicles (UAVs) operating autonomously. Obstacle avoidance algorithms either rely on global environment data or local sensor data. Local path planners react to unforeseen objects and plan purely on local sensor information. Similarly, animals need to find feasible paths based on local information about their surroundings. Therefore, their behavior is a valuable source of inspiration for path planning. Bumblebees tend to fly vertically over far-away obstacles and horizontally around close ones, implying two zones for different flight strategies depending on the distance to obstacles. This work enhances the local path planner 3DVFH* with this bio-inspired strategy. The algorithm alters the goal-driven function of the 3DVFH* to climb-preferring if obstacles are far away. Prior experiments with bumblebees led to two definitions of flight zone limits depending on the distance to obstacles, leading to two algorithm variants. Both variants reduce the probability of not reaching the goal of a 3DVFH* implementation in Matlab/Simulink. The best variant, 3DVFH*b-b, reduces this probability from 70.7 to 18.6% in city-like worlds using a strong vertical evasion strategy. Energy consumption is higher, and flight paths are longer compared to the algorithm version with pronounced horizontal evasion tendency. A parameter study analyzes the effect of different weighting factors in the cost function. The best parameter combination shows a failure probability of 6.9% in city-like worlds and reduces energy consumption by 28%. Our findings demonstrate the potential of bio-inspired approaches for improving the performance of local path planning algorithms for UAV.

Leukotriene A4 hydrolase (LTA4H) is the final and rate-limiting enzyme in the biosynthesis of pro-inflammatory leukotriene B4 (LTB4). Preclinical studies have provided strong evidence that LTA4H is an attractive drug target for the treatment of chronic inflammatory diseases. Here, we describe the transformation of compound 2, a fragment-like hit, into the potent inhibitor of LTA4H 3. Our strategy involved two key steps. First, we aimed to increase the polarity of fragment 2to improve its drug-likeness, particularly its solubility, while preserving both its promising potency and low molecular weight. Second, we utilized structural information and incorporated a basic amino function, which allowed for the formation of an essential hydrogen bond with Q136 of LTA4H and consequently enhanced the potency. Compound 3exhibited exceptional selectivity and showed oral efficacy in a KRN passive serum-induced arthritis model in mice. The anticipated human dose to achieve 90% target engagement at the trough concentration was determined to be 40 mg administered once daily.

Two series of pyrene-labeled poly(oligo(ethylene glycol) methyl ether methacrylate)s referred to as PyEG5–PEGnMA and PyC4–PEGnMA were prepared to probe the region surrounding the polymethacrylate backbone by using the fluorescence of the dye pyrene. PyEG5–PEGnMA and PyC4–PEGnMA were prepared by copolymerizing the EGnMA methacrylate monomers with penta(ethylene glycol) 1-pyrenemethyl ether methacrylate or 1-pyrenebutyl methacrylate, respectively. In organic solvents, the much longer 18 non-hydrogen atom linker connecting the pyrene moieties to the polymethacrylate backbone in the PyEG5–PEGnMA samples enabled the deployment of the pyrenyl labels into the solution. In water, however, an excited pyrene for PyEG5–PEGnMA was found to probe a same volume as for the PyC4–PEGnMA samples where a much shorter 6 non-hydrogen atom spacer connected pyrene to the backbone. Another surprising observation, considering that the hydrophobicity of pyrene induces strong pyrene aggregation for many pyrene-labeled water-soluble polymers (Py–WSPs) in water, was the little pyrene aggregation found for the PyEG5–PEGnMA and PyC4–PEGnMA samples in water. These effects could be related to the organic-like domain (OLD) generated by the oligo(ethylene glycol) side chains densely arranged around the polymethacrylate backbone of the polymeric bottlebrush (PBB). Additional fluorescence experiments conducted with the penta(ethylene glycol) 1-pyrenemethyl ether derivative indicated that the cylindrical OLD surrounding the polymethacrylate backbone had a chemical composition similar to that of ethylene glycol. Binding of hydrophobic pyrene molecules to unlabeled PEGnMA bottlebrushes in water further supported the existence of the OLD. The demonstration, that PEGnMA samples form an OLD in water, which can host and protect hydrophobic cargoes like pyrene, should lead to the development of improved PEGnMA-based drug delivery systems.

Antibody–drug conjugates (ADCs) are an established modality that allow for targeted delivery of a potent molecule, or payload, to a desired site of action. ADCs, wherein the payload is a targeted protein degrader, are an emerging area in the field. Herein we describe our efforts of delivering a Bruton’s tyrosine kinase (BTK) bifunctional degrader 1via a CD79b mAb (monoclonal antibody) where the degrader is linked at the ligase binding portion of the payload via a cleavable linker to the mAb. The resulting CD79b ADCs, 3and 4, exhibit in vitro degradation and cytotoxicity comparable with that of 1, and ADC 3can achieve more sustained in vivo degradation than intravenously administered 1with markedly reduced systemic exposure of the payload.

There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence.

ABSTRACT:In his fictitious letters Alciphron exploits the rich mythological and literary tradition starting from Homeric poetry, while he also employs a number of rhetorical devices and topoi typical of the Second Sophistic. The secondary bibliography mainly highlights how Alciphron was influenced by specific authors such as Homer, Menander, and Lucian. Through the discussion of various literary parallels, I illuminate the suggestion that Alciphron drew his material from a wide range of Classical, Hellenistic and Imperial authors and different literary genres in the composition of 1.1, which could be considered as a programmatic letter in his collection.

We describe explicitly all multisets of weights whose defining projective toric varieties are self-dual. In addition, we describe a remarkable and unexpected combinatorial behaviour of the defining ideals of these varieties. The toric ideal of a self-dual projective variety is weakly robust, that means the Graver basis is the union of all minimal binomial generating sets. When, in addition, the self-dual projective variety is defined by a non-pyramidal configuration, then the toric ideal is strongly robust, namely the Graver basis is a minimal generating set, therefore there is only one minimal binomial generating set which is also a reduced Gröbner basis with respect to every monomial order and thus, equals the universal Gröbner basis.

Oncogenic mutations in KRAS are present in ~95% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and are considered the initiating event of pancreatic intraepithelial neoplasia (PanIN) precursor lesions. While it is well established that KRAS mutations drive the activation of oncogenic kinase cascades during pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (PP2A) has been implicated in suppressing KRAS-driven cellular transformation and low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC. In the current study, we demonstrate that KRASG12Dinduces the expression of an endogenous inhibitor of PP2A activity, Cancerous Inhibitor of PP2A (CIP2A), and phosphorylation of the PP2A substrate, c-MYC. Consistent with these findings, KRASG12Dsequestered the specific PP2A subunit responsible for c-MYC degradation, B56α, away from the active PP2A holoenzyme in a CIP2A-dependent manner. During PDAC initiation in vivo, knockout of B56α promoted KRASG12Dtumorigenesis by accelerating acinar-to-ductal metaplasia (ADM) and the formation of PanIN lesions. The process of ADM was attenuated ex vivo in response to pharmacological re-activation of PP2A utilizing direct small molecule activators of PP2A (SMAPs). Together, our results suggest that suppression of PP2A-B56α through KRAS signaling can promote the MYC-driven initiation of pancreatic tumorigenesis.

This contribution proposes a nonlinear and dissipative infinite-dimensional port-Hamiltonian (PH) model for the dynamics of geometrically exact strings. The mechanical model provides a description of large deformations including finite elastic and inelastic strains in a generalized Maxwell model. It is shown that the overall system results from a power-preserving interconnection of PH subsystems. By using a structure-preserving mixed finite element approach, a finite-dimensional PH model is derived. Eventually, midpoint discrete derivatives are employed to deduce an energy-consistent time-stepping method, which inherits discrete-time dissipativity for the irreversible system. An example simulation illustrates the numerical properties of the present approach.

Despite an abundance of open data initiatives aimed to inform and empower “general” audiences, we still know little about the ways people outside of traditional data analysis communities experience and engage with public data and visualizations. To investigate this gap, we present results from an in-depth qualitative interview study with 19 participants from diverse ethnic, occupational, and demographic backgrounds. Our findings characterize a set of lived experiences with open data and visualizations in the domain of energy consumption, production, and transmission. This work exposes information receptivity — an individual's transient state of willingness or openness to receive information —as a blind spot for the data visualization community, complementary to but distinct from previous notions of data visualization literacy and engagement. We observed four clusters of receptivity responses to data- and visualization-based rhetoric: Information-Avoidant, Data-Cautious, Data-Enthusiastic, and Domain-Grounded. Based on our findings, we highlight research opportunities for the visualization community. This exploratory work identifies the existence of diverse receptivity responses, highlighting the need to consider audiences with varying levels of openness to new information. Our findings also suggest new approaches for improving the accessibility and inclusivity of open data and visualization initiatives targeted at broad audiences. A free copy of this paper and all supplemental materials are available at https://OSF.IO/MPQ32.

This article proposes a method to design network-aware flexibility requests for local flexibility markets. These markets are becoming increasingly important for distribution system operators (DSOs) to ensure grid safety while minimizing costs and public opposition to new network investments. Despite extended recent literature on local flexibility markets, little attention has been paid to quantifying the flexibility required at each location, considering physical network constraints (e.g. line and voltage limits). The method introduced uses a chance-constrained optimization model and a LinDistFlow approximation to consider both physical network constraints and uncertainty caused by renewable production or demand fluctuations. Unlike other methods, it avoids sharing sensitive grid data with the market operator. We compare our approach against a stochastic market-clearing mechanism which serves as a benchmark, and we derive analytical conditions for the performance of our method to determine flexibility requests. We show on two case studies that our method outperforms the stochastic market-clearing benchmark in terms of computation time while achieving comparable social welfare and costs for the DSOs. One of the case studies is conducted on an actual German distribution grid, showing that the proposed method can scale well to real-sized networks.

The immune microenvironment plays an important role in the regulation of diseases. The characterization of the cellular composition of immune cell infiltrates in diseases and respective models is a major task in pathogenesis research and diagnostics. For the assessment of immune cell populations in tissues, fluorescence-activated cell sorting (FACS) or immunohistochemistry (IHC) are the two most common techniques presently applied, but they are cost intensive, laborious, and sometimes limited by the availability of suitable antibodies. Complementary rapid qPCR-based approaches exist for the human situation but are lacking for experimental mouse models. Accordingly, we developed a robust, rapid RT-qPCR-based approach to determine and quantify the abundance of prominent immune cell populations such as T cells, helper T (Th) cells, cytotoxic T cells, Th1 cells, B cells, and macrophages in mouse tissues. The results were independently validated by the gold standards IHC and FACS in corresponding tissues and showed high concordance.

Graphical Abstract:

There is no consensus on defining relapse in schizophrenia, and scale-derived criteria with unclear clinical relevance are widely used. We aimed to develop an evidence-based scale-derived set of criteria to define relapse in patients with schizophrenia or schizoaffective disorder.

Numerous studies have been conducted among survivors of the genocide against the Tutsi on the prevalence of depression and post-traumatic stress disorder. However, thus far, no studies provide information on the frequency of comorbidity of these disorders, the prevalence of the new trauma-related diagnostic disorder known as complex post-traumatic stress disorder, and the role of social determinants, such as age, sex, marital status, employment category, education, and location, in the occurrence of these disorders. The present study was conducted to address these gaps. Genocide survivors (N= 261 participants; M= 46.30, SD= 11.95, females = 52.9%) took part in the study. They completed the International Trauma Questionnaire, the Public Health Depression Questionnaire, and the Harvard Trauma Questionnaire.Descriptive statistical analyses, bivariate analyses with two-tailed chi-square tests, and logistic regression were used to determine the prevalence of the above-mentioned disorders, comorbidity, and the associations between the social determinants and the assessed psychopathologies. Of the total sample, 47.1% presented with at least one of the assessed probable mental health disorders: 15.3% (n= 40) met the criteria for probable post-traumatic stress disorder, 15.3% (n= 40) for probable complex post-traumatic stress disorder, and 38.7% (n= 101) for probable depression. Of the participants with probable post-traumatic stress disorder and complex post-traumatic stress disorder, nearly half met the criteria for probable depression. Being married but not living with the partner was associated with probable complex post-traumatic stress disorder, and unemployment was associated with probable depression. Our findings suggest to clinicians and policymakers that they should consider comorbidity and social determinants in their interventions.

Queuosine is one of the most complex hypermodified RNA nucleosides found in the Wobble position of tRNAs. In addition to Queuosine itself, several further modified derivatives are known, where the cyclopentene ring structure is additionally modified by a galactosyl-, a mannosyl-, or a glutamyl-residue. While sugar-modified Queuosine derivatives are found in the tRNAs of vertebrates, glutamylated Queuosine (gluQ) is only known in bacteria. The exact structure of gluQ, particularly with respect to how and where the glutamyl side chain is connected to the Queuosine cyclopentene side chain, is unknown. Here we report the first synthesis of gluQ and, using UHPLC-MS-coinjection and NMR studies, we show that the isolated natural gluQ is the α-allyl-connected gluQ compound.

We describe the discovery and characterization of the supersoft topical JAK inhibitor 3(R), which is potent in biochemical and cellular assays as well as in human skin models. In blood, the neutral ester 3(R)is rapidly hydrolyzed (t1/2∼ 6 min) to the corresponding charged carboxylic acid 4exhibiting >30-fold reduced permeability. Consequently, acid 4does not reach the intracellular JAK kinases and is inactive in cellular assays and in blood. Thus, hydrolysis by blood esterases leads to the rapid deactivation of topically active ester 3(R)at a rate beyond the maximal hepatic clearance.

We report an inelastic neutron scattering (INS) study on the low-energy magnetic excitations of Ba2CoGe2O7 single crystals under applied magnetic fields for several fixed temperatures. We have observed a sizable spin gap of ≈0.105 meV for the acoustic mode at 2.2 K under zero magnetic fields, whereas no changes in energy of the optical modes at the magnetic zone center are observed under varying temperatures. However, the spin gap of the acoustic mode at finite fields also evolves under varying temperatures and the gap energy decreases with increasing temperature. Interestingly, the difference between the spin gap at 2.2 and 4.6 K is about ≈0.025 meV for all the applied fields of 0.35, 1, and 5 T. Our results enlighten the discussion in detail on understanding the origin of the spin gap in Ba2CoGe2O7.

Side-effects of psychiatric medication impair quality of life and functioning. Furthermore, they contribute to morbidity, mortality, stigma, and poor treatment concordance resulting in relapse of psychiatric illness. Guidelines recommend discussing side-effects with patients when making treatment decisions, but a synthesis of antidepressant and antipsychotic side-effects to guide this process is missing, and considering all side-effects is a complex, multidimensional process. We aimed to create comprehensive databases of antipsychotic and antidepressant side-effects, and a digital tool to support database navigation.

Background:Closed incision negative pressure therapy (ciNPT) devices may reduce wound healing complications when applied to closed surgical incisions. The aim of this review was to assess the effects of ciNPT versus standard dressings in patients undergoing primary closure of high tension, lower transverse abdominal incisions. Methods:This review was registered a priori on PROSPERO (CRD42021252048). A search of the following databases was performed in February 2021: Medline, EMBASE, and CENTRAL. Unpublished trials were searched using clinicaltrials.gov. All randomized and nonrandomized studies comparing ciNPT to standard dressings were included. Two independent reviewers performed screening and data extraction. Outcomes evaluated the incidence of wound dehiscence, surgical site infection, total abdominal complications, time to drain removal, and seroma formation. Main Results:Ten studies were included in quantitative and narrative synthesis. Observational study evidence suggests ciNPT likely reduces the incidence of wound dehiscence (odds ratio [OR] 0.57 [0.44-0.96], P= .03) and total abdominal complications (OR 0.34 [0.21-0.54], P< .01). Decreased incidence of seroma formation favored ciNPT (OR 0.65 [0.24-1.76], P= .40); however, this did not achieve significance. Randomized and non-randomized study evidence was very uncertain about the effect of ciNPT on the remaining outcomes. Conclusions:The current best randomized study evidence is very uncertain about the effect of ciNPT on these outcomes. Observational study evidence suggests ciNPT likely results in a statistically significant reduction in abdominal wound dehiscence and total abdominal complications. Additional randomized trials are warranted to limit the impact of bias on the overall certainty of the evidence.

Missbrauchserfahrungen in frühen Lebensjahren können sich bis ins hohe Lebensalter negativ auf die Betroffenen auswirken. Heute existiert vergleichsweise wenig systematisches Wissen im Hinblick auf (un)spezifische Traumafolgen bei älteren Betroffenen. Zusätzlich besteht wenig Wissen bezüglich (relativ) unversehrter langfristiger Verläufe nach traumatischen Kindheitserfahrungen. Um einerseits diesen Forschungsrückstand aufzuholen und andererseits dabei zu helfen, ein dunkles Kapitel der Schweizer Geschichte aufzuarbeiten, wurden am Psychologischen Institut der Universität Zürich mehrere Studien mit ehemaligen Betroffenen von „Fürsorgerischen Zwangsmaßnahmen und Fremdplatzierung“ durchgeführt. Ziel war es herauszufinden, inwieweit solche Erfahrungen mit der körperlichen und psychischen Gesundheit im Alter zusammenhängen.

Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare prevention.

Modern embedded and cyber-physical applications consist of critical and non-critical tasks co-located on multiprocessor systems on chip (MPSoCs). Co-location of tasks results in contention for shared resources, resulting in interference on interconnect, processing units, storage, etc. Hence, machine learning-based resource managers must operate even non-critical tasks within certain constraints to ensure proper execution of critical tasks. In this paper we demonstrate and evaluate countermeasures based on backup policies to enhance rule-based reinforcement learning to enforce constraints. Detailed experiments reveal the CPUs’ performance degradation caused by different designs, as well as their effectiveness in preventing constraint violations. Further, we exploit the interpretability of our approach to further improve the resource manager’s operation by adding designers’ experience into the rule set.

Multidimensional channel sounding measures the geometrical structure of mobile radio propagation. The parameters of a multipath data model in terms of directions, time-of-flight, and Doppler shift are estimated from observations in frequency, time, and space. A maximum likelihood estimation framework allows joint high resolution in all dimensions. The prerequisite for this is an appropriate parametric data model that represents the multipath propagation correctly. At the same time, a device data model is necessary that typically results from calibration measurements. The used model should be as simple as possible, since its structure has a considerable effect on the estimation effort. For instance, the inherent effort in parameter search is reduced if the influence of the parameters is kept independent. Therefore, the data model is characterized by several approximations. The most important is the “narrowband assumption,” which assumes a low relative bandwidth and also avoids considering any frequency response in magnitude and phase. We extend the well-known multidimensional Richter maximization approach (RIMAX) parameter estimation framework by including proper frequency responses. The advantage reveals itself with high bandwidth in the mmWave and sub-THz range. It allows for a more realistic modeling of antenna arrays, and it breaks with the usual narrowband model and allows a better modeling of mutual coupling and time delay effects. If the interacting object extends over several delay bins (hence, an extended target in radar terminology), we propose a model that assigns a short delay spread and a frequency response to the propagation path that associates it with the respective object. We verify the validity of the device model by numerical experiments on simulated and measured antenna data and compare it with RIMAX. In addition, we use synthetic data based on ray-tracing results and measurements both ranging from 27.0 to $\mathrm {33 \text {G} \text {Hz} }$ with known ground-truth information and show that the proposed estimator delivers better performance for higher relative bandwidths than the conventional RIMAX implementation.

This publication proposes a parametric data model and a gradient-based maximum likelihood estimator suitable for the description of delay-dispersive responses of multiple dynamic ultrawideband (UWB)-radar targets. The target responses are estimated jointly with the global target parameters range and velocity. The large relative bandwidth of UWB has consequences for model-based parameter estimation. On the one hand, the Doppler effect leads to a dispersive response in the Doppler spectrum and to a coupling of the target parameters that both need to be considered during modeling and estimation. On the other hand, the shape of an extended target results in a dispersive response in range, which can be resolved by the radar resolution. We consider this extended response as a parameter of interest, e.g., for the purpose of target recognition. Hence, we propose an efficient description and estimation of it by a finite impulse response (FIR) structure only imposing a restriction on the target’s dispersiveness in range. We evaluate the approach on simulations, compare it to state-of-the-art solutions, and provide a validation of the FIR model on measurements of a static scenario.

To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease‐modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team‐based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision‐making when applying these recommendations.

Despite the availability of disability resource centers and reasonable accommodations to facilitate access among teacher candidates with disabilities, research has shown that access alone may not be conducive to equitable educational experiences that promote program retention and completion. The purpose of this systematic review of the literature was to synthesize existing research on the experiences of teacher candidates with disabilities in teacher preparation programs and present implications and future directions for research, policy, and practice in higher education disability resources and special education teacher preparation to advance both access and equity in these settings. Results from five total articles showed that teacher candidates with disabilities experienced several barriers to access in their teacher preparation programs that negatively impacted their personal and professional outcomes. The authors conclude with a discussion of future directions for research, policy, and practice in both special education teacher preparation and higher education disability resources.

The human T cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that persists as a provirus in the genome of infected cells and can lead to adult T cell leukemia (ATL). Worldwide, more than 10 million people are infected and approximately 5% of these individuals will develop ATL, a highly aggressive cancer that is currently incurable. In the last years, genome editing tools have emerged as promising antiviral agents. In this proof-of-concept study, we use substrate-linked directed evolution (SLiDE) to engineer Cre-derived site-specific recombinases to excise the HTLV-1 proviral genome from infected cells. We identified a conserved loxP-like sequence (loxHTLV) present in the long terminal repeats of the majority of virus isolates. After 181 cycles of SLiDE, we isolated a designer-recombinase (designated RecHTLV), which efficiently recombines the loxHTLV sequence in bacteria and human cells with high specificity. Expression of RecHTLV in human Jurkat T cells resulted in antiviral activity when challenged with an HTLV-1 infection. Moreover, expression of RecHTLV in chronically infected SP cells led to the excision of HTLV-1 proviral DNA. Our data suggest that recombinase-mediated excision of the HTLV-1 provirus represents a promising approach to reduce proviral load in HTLV-1-infected individuals, potentially preventing the development of HTLV-1-associated diseases.

To evaluate the association of baseline factors with rehabilitation dose and the association of rehabilitation dose with meaningful change in physical function, pain, and fatigue over 6 months among adults with rheumatoid arthritis (RA). Using data from the National Databank for Rheumatic Diseases registry, we extracted baseline characteristics and self‐reported physical function (Health Assessment Questionnaire), pain (visual analog scale [VAS]), fatigue (VAS), rehabilitation dose (low: 1–2 visits, medium: 3–8 visits, high: >8 visits), and follow‐up outcomes 6 months later. Changes in clinical outcomes were categorized as improved, no change, or worsened. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using proportional odds logistic regression models to examine the association of the baseline factors with rehabilitation dose and the association of rehabilitation dose with changes in clinical outcomes, adjusting for potential confounders. The sample included 1,381 adults with a new episode of rehabilitation (dose: low 27%, medium 42%, high 31%). Worse baseline physical function (adjusted OR 1.29 [95% CI 1.04–1.60]), but not pain (adjusted OR 1.04 [95% CI 0.99–1.10]) or fatigue (adjusted OR 0.98 [95% CI 0.93–1.03]), were associated with a higher rehabilitation dose. A high rehabilitation dose was associated with a favorable change in physical function (OR 1.51 [95% CI 1.14–1.98]), pain (OR 1.44 [95% CI 1.06–1.96]), and fatigue (OR 1.45 [95% CI 1.06–1.99]) compared to a low dose; only the association with physical function change persisted in adjusted models (adjusted OR 1.41 [95% CI 1.03–1.92]). Using real‐world data, this study supports a higher rehabilitation dose to improve physical function in adults with RA.

Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long‐term efficacy of antipsychotic drugs in acutely ill patients using network meta‐analysis. We searched the Cochrane Schizophrenia Group register up to March 6, 2022 for randomized, blinded trials of at least 6‐month duration on all second‐generation and 18 first‐generation antipsychotics. The primary outcome was change in overall symptoms of schizophrenia; secondary outcomes were all‐cause discontinuation; change in positive, negative and depressive symptoms; quality of life, social functioning, weight gain, antiparkinson medication use, akathisia, serum prolactin level, QTc prolongation, and sedation. Confidence in the results was assessed by the CINeMA (Confidence in Network Meta‐Analysis) framework. We included 45 studies with 11,238 participants. In terms of overall symptoms, olanzapine was on average more efficacious than ziprasidone (standardized mean difference, SMD=0.37, 95% CI: 0.26‐0.49), asenapine (SMD=0.33, 95% CI: 0.21‐0.45), iloperidone (SMD=0.32, 95% CI: 0.15‐0.49), paliperidone (SMD=0.28, 95% CI: 0.11‐0.44), haloperidol (SMD=0.27, 95% CI: 0.14‐0.39), quetiapine (SMD=0.25, 95% CI: 0.12‐0.38), aripiprazole (SMD=0.16, 95% CI: 0.04‐0.28) and risperidone (SMD=0.12, 95% CI: 0.03‐0.21). The 95% CIs for olanzapine versus aripiprazole and risperidone included the possibility of trivial effects. The differences between olanzapine and lurasidone, amisulpride, perphenazine, clozapine and zotepine were either small or uncertain. These results were robust in sensitivity analyses and in line with other efficacy outcomes and all‐cause discontinuation. Concerning weight gain, the impact of olanzapine was higher than all other antipsychotics, with a mean difference ranging from –4.58 kg (95% CI: –5.33 to –3.83) compared to ziprasidone to –2.30 kg (95% CI: –3.35 to –1.25) compared to amisulpride. Our data suggest that olanzapine is more efficacious than a number of other antipsychotic drugs in the longer term, but its efficacy must be weighed against its side effect profile.

A series of nine pyrene-labeled poly(oligo(ethylene glycol) methyl ether methacrylate)s (Py-PEGnMAs) with nequal to 0–5, 9, 16, and 19 were prepared by random radical copolymerization of 1-pyrenebutyl methacrylate and nine different EGnMA monomers. The process of pyrene excimer formation (PEF) in the Py-PEGnMA samples was characterized in acetone, THF, toluene, N,N-dimethylformamide (DMF), dioxane, and dimethyl sulfoxide (DMSO). The fluorescence decays of all Py-PEGnMA samples were acquired in the six solvents and analyzed with the fluorescence blob model (FBM) to yield the number Nblobof structural units (SU) in the subvolume of the polymer coil probed by an excited pyrene and referred to as a blob, and the rate constant kblobdescribing the encounters between two SU bearing an excited and a ground-state pyrenyl label located inside a same blob. Nbloband kblobremained constant with pyrene content for a same series of Py-PEGnMA samples. After averaging Nbloband kblobover all pyrene contents for a same Py-PEGnMA series, ⟨Nblob⟩ and the product ⟨kblob× Nblob⟩ were found to decrease with increasing side chain length reflecting a progressive stiffening and decrease in the internal dynamics of the polymethacrylate backbone, respectively. ⟨Nblob⟩ and ⟨kblob× Nblob⟩ could be parametrized as a function of the molecular weight of an SU and the solvent viscosity. The parametrized form of ⟨Nblob⟩ was applied to determine the persistence length (lp) of the PEGnMA samples using the Kratky–Porod equation. lpwas found to increase linearly with the square of the side chain length of the PEGnMA samples, as expected theoretically. The parametrized form of ⟨kblob× Nblob⟩ was used as a calibration curve against which the internal dynamics of several polypeptides and poly(methyl acrylate) could be compared in DMSO. This study illustrates the ability of PEF measurements to determine the persistence length and quantify the internal dynamics of polymers in solution, two important parameters in the characterization of macromolecules.

We used 14 years of state licensure and classroom data from Virginia to follow 19,878 special education teachers (SETs) who completed either the alternative route (AR) internship or traditional programs. Findings reveal that a greater percentage of SETs of color participated in AR programs compared to traditional licensure programs, while a greater percentage of White SETs completed traditional programs. SETs of color attained approximately three fewer years of service time if they completed the AR program compared to traditional programs. For White SETs, a difference of less than 1 year was found. For SETs from AR programs who did not complete 27 credit hours of university coursework, attrition occurred at higher rates within the first 3 years of service. Implications for future research on AR internship programs and teachers of color are provided, informing both policy and practice.

The objective of this work was to assess the energy consumption of a novel remanufacturing method that utilizes mechanically-generated feedstock for directed energy deposition. Gas-atomization is the state-of-the-art production process for directed energy deposition feedstock, and for this work was incorporated into a remanufacturing process path to provide a comparison method. Specific energy consumption models of remanufacturing utilizing both of these proposed process paths were developed and applied to a case study to investigate energy saving opportunities for future manufacturing paradigms. The energy modelling was done in three stages. First, the mechanically-generated feedstock production energy consumption model was generated from experimental observation. Second, the gas-atomized feedstock production energy consumption model was generated from a combination of experimental observation, reported estimates from the manufacturer, and data found in the literature. Lastly, the energy consumption model of directed energy deposition was derived from experimental observation and compares favorably with reported estimates in the literature. With the models, the specific energy consumption in the two process paths were compared and their application was demonstrated by estimating the energy consumption to remanufacture a bracket. The two feedstock production methods had similar specific energy consumptions. The specific energy consumption of the directed energy deposition process was the greatest component in the respective remanufacturing paths by an order of magnitude; increasing deposition rate is the most important factor for lowering the overall specific energy consumption. The analyzed remanufacturing technologies were estimated to consume less energy than replacement when repairing up to approximately 15% of the original part’s mass.

Objective The aim of this study was to examine internal responsiveness and estimate minimally important differences (MIDs) for CLEFT-Q scales.Design In this prospective cohort study, participants completed the CLEFT-Q appearance and health-related quality of life (HRQL) scales before and six months after cleft-related surgery.Setting Seven cleft centres in Canada, USA and UK participated.Patients/Participants Patients were ages 8–29 years with CL/P.Interventions Patients underwent rhinoplasty, orthognathic or cleft lip scar revision surgery.Main Outcome Measure(s) Internal responsiveness was examined using Cohen's d effect sizes (ESs) based on the following interpretation: 0.20–0.49 small, 0.50–0.79 moderate and ≥ 0.80 large. MIDs were estimated using two distribution-based approaches.Results Participants had a rhinoplasty (n = 31), orthognathic (n = 21) or cleft lip scar revision (n = 18) surgery. Most participants were males (56%) and aged 8–11 years (41%). Following rhinoplasty, ESs were larger for the nose (0.92, p = 0.001) and nostrils (0.94, p < 0.001) scales than for the face scale (0.51, p = 0.003). MIDs ranged between 6.2–10.4. For orthognathic surgery, larger ES was observed for the jaws scale (1.80, p < 0.001) compared with the teeth (1.16, p < 0.001), face (1.15, p = 0.001) and lips (0.94, p < 0.001) scales. MIDs ranged between 5.9–14.4. In the cleft lip scar revision sample, the largest ES was observed for the nose scale (0.76, p = 0.03), followed by lips (0.58, p = 0.009) and cleft lip scar (0.50, p = 0.043) scales. MIDs ranged between 6.4–12.3.Conclusions CLEFT-Q detected change in key outcomes for three cleft-specific surgeries, providing evidence of its responsiveness. Estimated MIDs will aid in interpreting this PROM.