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INTRODUCTION: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m(2) in the avacopan group and 4.1 ml/min per 1.73 m(2) in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m(2). METHODS: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. RESULTS: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m(2). At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m(2) in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m(2), respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. CONCLUSION: Among patients with baseline eGFR ≤20 ml/min per 1.73 m(2) in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

In this work, strontium-free copper-doped nickelates, La2Ni1-xCuxO4 (x=0.1-0.3), were synthesized using solid state synthesis method and tested as potential oxygen electrodes in solid oxide electrolysis cells (SOEC). Similar to the parent compound, the Ruddlesden-Popper (RP) La2NiO4 oxide, the Cu-doped compositions were confirmed to crystallize with tetragonal crystal structure with I4/mmm space group. The electrochemical performance of La2Ni1-xCuxO4 electrodes was studied using Ni-YSZ electrode-supported button cells in SOEC mode and compared to the state-of-the-art (La0.6Sr0.4)0.95Co0.0.8O3-δ (LSCF)-doped ceria composite electrodes. Electrochemical tests were conducted at 750oC with the Ni-YSZ hydrogen electrode exposed to 50% steam in hydrogen. The polarization resistance of SOEC with the La2Ni0.8Cu0.2O4 (LNCuO-20) electrode was lower than that with LSCF. LNCuO-20 showed stable current density output over 800 hours tested, while cell with LSCF showed more degradation.

Exploring the transformational potential of FHE and the path toward adoption of its "stack."

The utility of teacher evaluation depends on meaningful teacher engagement with evaluation processes. However, critics of traditional tenure policies suggest that tenure nullifies teacher engagement with practices to improve performance. This study investigates whether tenured teachers exhibit perceptions that reflect disengagement with evaluation and feedback and whether perceptions of evaluation vary based on teachers having received tenure under a reformed system that restricts lifetime protections conditional on continual high evaluation scores. Using statewide administrative and survey data from Tennessee, the study employs propensity score methods to isolate differences in perceptions between comparable groups of tenured and untenured teachers. Results show that tenured teachers report more negative perceptions of evaluation in their district; however, this difference is concentrated among those who received permanent tenure status prior to the reformed tenure system. The study concludes by discussing implications and directions for future research.

The article deals with the most important changes in the independence and systemic autonomy of local self-government units of the 2018–2023 term. Both normative solutions and actual actions and behaviours that have a fundamental impact on the functioning of local self-government will be analysed. For a more complete picture of the current term, it will be necessary to briefly characterise the changes introduced after 2015. It is also important for the overall analysis to look from the perspective of those currently in power and characterise their vision of the state and the role of local government in the political system. The idea of a strong, effective state determines the perception of the role of local government and the relationship at the interface between local government and government administration.

In the last two decades in the United States (US), the previous research has focused on medication optimization, including polypharmacy. Polypharmacy is associated with several negative outcomes, which may be resolved by deprescribing medications that are no longer necessary. Although deprescribing is a critical aspect of a pharmacist’s role, some studies have demonstrated that student pharmacists are less familiar with their future role in deprescribing. Thus, this study aimed to explore student pharmacists’ perceptions of deprescribing in the pharmacy curriculum. This qualitative study was conducted with student pharmacists enrolled in three Doctor of Pharmacy (Pharm.D.) programs in the US. The participants, all student pharmacists at the time of the study, were identified via an email requesting their voluntary participation in a focus group study. The focus groups were conducted via an online platform over three months in 2022, and recruitment continued until thematic saturation was obtained. Using thematic analysis, the corpus of the transcribed data was imported into Dedoose®, a qualitative software that facilitated the analysis. Three themes emerged from the data: (1) the importance of deprescribing; (2) barriers to deprescribing; (3) education recommendations. The data highlight that the student pharmacists believe integrating deprescribing content into the clinical, didactic, and simulation education would help them overcome the identified obstacles. Colleges of pharmacy should consider emphasizing the importance of deprescribing in their curriculum, creating programs to assist future pharmacists in addressing the barriers to deprescribing, and adopting the suggested educational strategies to improve the deprescribing education that is offered.

For the estimation and further optimization of the residual stress and distortion state in additively manufactured structures during and after the wire arc additive manufacturing (WAAM) process, thermomechanical simulation can be applied as a numerical tool. In addition to the detailed modelling of key process parameters, the used material model and material data have a major influence on the accuracy of the numerical analysis. The material behaviour, in particular the viscoplastic behaviour of the titanium alloy Ti-6Al-4 V which is commonly used in aerospace, is investigated within this work. An extensive material characterization of the viscoplastic material behaviour of the WAAM round specimen is carried out conducting low cycle fatigue (LCF) and complex low cycle fatigue (CLCF) tests in a wide temperature range. An elasto-viscoplastic Chaboche material model is parameterised, fitted, and validated to the experimental data in the investigated temperature range. Subsequently, the material model is implemented in the thermomechanical simulation of a representative, linear ten-layer WAAM structure. To finally determine the effect of the fitted material model on the estimation accuracy of residual stress and distortion, simulation results using the standard material model and the elaborated Chaboche model from this study are compared to experimental data in the substrate. The thermomechanical simulation with the Chaboche model reveals a better agreement with the experimental distortion and residual stress state, whereby the standard material model tends to an overestimation. The estimation accuracy with respect to the maximum distortion is improved from an error of 60% with the standard model to an acceptable error of about 6% using the elaborated model. Additionally, the estimated residual stress state shows a sound agreement to the experimental residual stress in the substrate.

Facial nerve paralysis or Bell's palsy have been suggested as possible consequences of SARS-CoV-2 infections, as well as possible side effects of COVID-19 vaccinations. Google Trends data have been used to evaluate worldwide levels of public awareness for these topics for pre- and post-pandemic years. The results demonstrate a relatively low public interest in facial nerve paralysis in comparison to other more common COVID-19 related topics. Some peaks of interest in Bell's palsy can most likely be explained as triggered by the media. Therefore, Google Trends has shown public's relatively low awareness of this rare neurological phenomenon during the pandemic.

Purpose Magnetic resonance imaging (MRI) scan time remains a limited and valuable resource. This study evaluates the diagnostic performance of a deep learning (DL)-based accelerated TSE study protocol compared to a standard TSE study protocol in ankle MRI. Material and methods Between October 2020 and July 2021 forty-seven patients were enrolled in this study for an intraindividual comparison of a standard TSE study protocol and a DL TSE study protocol either on a 1.5 T or a 3 T scanner. Two radiologists evaluated the examinations regarding structural pathologies and image quality categories (5-point-Likert-scale; 1 = “non diagnostic”, 5 = “excellent”). Results Both readers showed almost perfect/perfect agreement of DL TSE with standard TSE in all analyzed structural pathologies (0.81–1.00) with a median “good” or “excellent” rating (4–5/5) in all image quality categories in both 1.5 T and 3 T MRI. The reduction of total acquisition time of DL TSE compared to standard TSE was 49% in 1.5 T and 48% in 3 T MRI to a total acquisition time of 5 min 41 s and 5 min 46 s. Conclusion In ankle MRI the new DL-based accelerated TSE study protocol delivers high agreement with standard TSE and high image quality, while reducing the acquisition time by 48%.

PURPOSE: The International Alliance of Academies of Childhood Disability created a COVID-19 Task Force with the goal of understanding the global impact of COVID-19 on children with disabilities and their families. The aim of this paper is to synthesize existing evidence describing the impact of COVID-19 on people with disabilities, derived from surveys conducted across the globe. METHODS: A descriptive environmental scan of surveys was conducted. From June to November 2020, a global call for surveys addressing the impact of COVID-19 on disability was launched. To identify gaps and overlaps, the content of the surveys was compared to the Convention on the Rights of the Child and the International Classification of Functioning, Disability and Health. RESULTS: Forty-nine surveys, involving information from more than 17,230 participants around the world were collected. Overall, surveys identified that COVID-19 has negatively impacted several areas of functioning - including mental health, and human rights of people with disabilities and their families worldwide. CONCLUSION: Globally, the surveys highlight that impact of COVID-19 on mental health of people with disabilities, caregivers, and professionals continues to be a major issue. Rapid dissemination of collected information is essential for ameliorating the impact of COVID-19 across the globe.

Objectives The WHO’s standardized measuring unit, “binding antibody units per milliliter (BAU/mL),” should allow the harmonization of quantitative results by different commercial Anti-SARS-CoV-2 immunoassays. However, multiple studies demonstrate inter-assay discrepancies. The antigenic changes of the Omicron variant affect the performance of Spike-specific immunoassays. This study evaluated the variation of quantitative Anti-SARS-CoV-2-Spike antibody measurements among 46, 50, and 44 laboratories in three rounds of a national external quality assessment (EQA) prior to and after the emergence of the Omicron variant in a diagnostic near-to-real-life setting. Methods We analyzed results reported by the EQA participant laboratories from single and sequential samples from SARS-CoV-2 convalescent, acutely infected, and vaccinated individuals, including samples obtained after primary and breakthrough infections with the Omicron variant. Results The three immunoassays most commonly used by the participants displayed a low intra-assay and inter-laboratory variation with excellent reproducibility using identical samples sent to the participants in duplicates. In contrast, the inter-assay variation was very high with all samples. Notably, the ratios of BAU/mL levels quantified by different immunoassays were not equal among all samples but differed between vaccination, past, and acute infection, including primary infection with the Omicron variant. The antibody kinetics measured in vaccinated individuals strongly depended on the applied immunoassay. Conclusions Measured BAU/mL levels are only inter-changeable among different laboratories when the same assay was used for their assessment. Highly variable ratios of BAU/mL quantifications among different immunoassays and infection stages argue against the usage of universal inter-assay conversion factors.

OBJECTIVE American bison (Bison bison) quarantine protocols were established to prevent transmission of brucellosis outside the Greater Yellowstone Area, while allowing for distribution of wild bison for conservation and cultural purposes. Quarantine standards require rigorous testing over 900 days which has led to the release of over 200 bison to Native American tribes. Standards were evaluated using 15 years of laboratory and management data to minimize the burden of testing and increase the number of brucellosis-free bison available for distribution. ANIMALS All bison (n = 578) from Yellowstone National Park were corralled by the National Park Service and United States Department of Agriculture. PROCEDURES A statistical and management evaluation of the bison quarantine program was performed. Bayesian latent-class modeling was used to predict the probability of nondetection of a seroreactor at various time points, as well as the probability of seroconversion by days in quarantine. RESULTS At 300 days, 1 in 1,000 infected bison (0.0014 probability) would not be detected but could potentially seroconvert; the seroconversion model predicted 99.9% would seroconvert by day 294, and 12.8% of bison enrolled in quarantine would seroconvert over time. Using a 300-day quarantine period, it would take 30 years to potentially miss 1 seroreactor out of over 8,000 bison enrolled in the quarantine program. CLINICAL RELEVANCE Reducing the quarantine program requirements from over 900 days to 300 days would allow management of quarantined bison in coordination with seasonal movement of bison herds and triple the number of brucellosis-free bison available for distribution.

OBJECTIVE The geographical distribution of feline cytauxzoonosis is expanding in the US. Clinical signs of feline cytauxzoonosis, including lethargy, anorexia, and icterus, are similar to hepatic lipidosis and cholangiohepatitis. Hematologic and serum biochemical abnormality patterns may assist practitioners in prioritizing feline cytauxzoonosis as a differential diagnosis over hepatic lipidosis and cholangiohepatitis. SAMPLE Hematology and serum biochemical profiles of cats with naturally acquired feline cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. PROCEDURES Retrospective search and analysis of the Kansas State Veterinary Diagnostic Laboratory or Kansas State University Veterinary Health Center records between January 2007 and June 2018 for cats with cytauxzoonosis, hepatic lipidosis, or cholangiohepatitis. RESULTS Patients with acute feline cytauxzoonosis presented with frequent nonregenerative anemia (20/28 [71%]), leukopenia (23/28 [82%]), thrombocytopenia (23/23 [100%]), hyperbilirubinemia (27/28 [97%]), hypoalbuminemia (26/28 [93%]), reduced (18/28 [64%]) or low normal (10/28 [36%]) serum ALP activity, and hyponatremia (23/28 [82%]). Reduced ALP activity was unique to cats with feline cytauxzoonosis relative to hepatic lipidosis and cholangiohepatitis. No correlation between the severity of anemia and the magnitude of hyperbilirubinemia was identified in feline cytauxzoonosis patients. CLINICAL RELEVANCE The combination of nonregenerative anemia, leukopenia, thrombocytopenia, hyperbilirubinemia, and reduced serum ALP activity in icteric cats may increase the clinical suspicion, but is not pathognomonic, for acute feline cytauxzoonosis. Hematologic and serum biochemical abnormalities of naturally acquired feline cytauxzoonosis are like those reported with feline bacterial sepsis. Blood smear evaluation for intraerythrocytic Cytauxzoon felis piroplasms, tissue aspirates for schizont-laden macrophages, and/or molecular testing are required to diagnose feline cytauxzoonosis.

Design is a comprehensive discipline encompassing several processes, tools, and methodologies, to create and communicate solutions. This requires research, gathering evidence, creative thinking, designing, refining, testing and, foremost, conveying an idea to a specific audience with a purpose. Over the past decades, higher education institutions and, especially, design schools have deployed Computer Aided Design (CAD) software into the curricula. This undertaking provided students with new tools to design, develop and implement in a fast-paced society. Digital technology has undoubtedly caused changes to the design process that have still to be fully understood. (Oxman, 2006, pp. 229-265).

In fused filament fabrication (FFF), it is important to control the extrusion process for different materials and extruder hardware precisely. The effective extrusion force on the nozzle allows the characterization of the flow behaviour of the molten polymer. Therefore, integrating compact force sensors into the extrusion unit allows the identification of suitable process windows for different materials and the evaluation of hardware. However, actual setups are not compact and restriction-free. This paper presents a new compact and concentric setup, which allows an accurate measurement of the forces in the extruder avoiding parasitic effects. Furthermore, the test rig and the calibration process including influencing factors such as filament contact force and extrusion height is described. On this basis, a varying parameter study using different nozzles, feeding velocities, and temperatures is conducted. The recorded values of the extrusion force are compared with the literature values and the flow behaviour is assigned to the corresponding nozzle geometry. It has been shown that the calibrated test rig is able to measure the extrusion force with sufficient accuracy. These measurements correspond to comparable literature values. The boundary conditions of feeding velocity for processing a specific material and nozzle are determined. In this way, requirements such as the fastest or a uniform extrusion can be specifically served by varying the corresponding parameters. An evaluation of the effects in the nozzles results in a nozzle performance overview.

Protein translation is tightly and precisely controlled by multiple mechanisms including upstream open reading frames (uORFs), but the origins of uORFs and their role in maize are largely unexplored. In this study, an active transposition event was identified during the propagation of maize inbred line B73. The transposon, which was named BTA for ‘B73 active transposable element hAT’, creates a novel dosage-dependent hypomorphic allele of the hexose transporter gene ZmSWEET4c through insertion within the coding sequence in the first exon, and results in reduced kernel size. The BTA insertion does not affect transcript abundance but reduces protein abundance of ZmSWEET4c, probably through the introduction of a uORF. Furthermore, the introduction of BTA sequence in the exon of other genes can regulate translation efficiency without affecting their mRNA levels. A transposon capture assay revealed 79 novel insertions for BTA and BTA-like elements. These insertion sites have typical euchromatin features, including low levels of DNA methylation and high levels of H3K27ac. A putative autonomous element that mobilizes BTA and BTA-like elements was identified. Together, our results suggest a transposon-based origin of uORFs and document a new role for transposable elements to influence protein abundance and phenotypic diversity by affecting the translation rate.

This study examined the knowledge and perceptions of speech-language pathology students working with older adults before and after their participation in a feeding training program. A secondary objective evaluated the feeding training program in terms of improving students' knowledge and skills. A repeated measures design was used to assess changes in perceptions and knowledge over time of students participating in a feeding training program assisting older adults at a skilled nursing facility. Twenty-four students in the communication sciences and disorders department from a university were recruited. Data were collected on the perceptions of working with older adults, knowledge of feeding and swallowing, and the evaluation of the program. Participants reported feeling less fearful of assisting older adults with feeding issues and appeared to acquire a higher level of knowledge in certain areas post-training. Analysis of the evaluation forms revealed that students were positive about their experience. The findings provide additional support that perceptions become more favorable following early exposure to older adults through participation in service-learning experiences. This study supplements the literature about the knowledge and perceptions of speech-language pathology students working with older adults. This information may be used to improve the quality of care for older adults in various settings.

The emergence of a plethora of new tobacco products marketed as being less harmful than smoking, such as electronic cigarettes and heated tobacco products, and the increased popularity of recreational marijuana have raised concerns about the potential cardiovascular risk associated with their use.The purpose of this study was to investigate whether the use of novel tobacco products or marijuana can cause the development of proarrhythmic substrate and eventually lead to arrhythmias.Rats were exposed to smoke from tobacco, marijuana, or cannabinoid-depleted marijuana, to aerosol from electronic cigarettes or heated tobacco products, or to clean air once per day for 8 weeks, following by assays for blood pressure, cardiac function, ex vivo electrophysiology, and histochemistry.The rats exposed to tobacco or marijuana products exhibited progressively increased systolic blood pressure, decreased cardiac systolic function with chamber dilation, and reduced overall heart rate variability, relative to the clean air negative control group. Atrial fibrillation and ventricular tachycardia testing by ex vivo optical mapping revealed a significantly higher susceptibility to each, with a shortened effective refractory period and prolonged calcium transient duration. Histological analysis indicated that in all exposure conditions except for air, exposure to smoke or aerosol from tobacco or marijuana products caused severe fibrosis with decreased microvessel density and higher level of sympathetic nerve innervation.These pathophysiological results indicate that tobacco and marijuana products can induce arrhythmogenic substrates involved in cardiac electrical, structural, and neural remodeling, facilitating the development of arrhythmias.

The revered tradition of amateurism has transformed due to legal and legislative challenges initiated by the name, image, and likeness landscape. In contrast to the traditional National Collegiate Athletic Association model, college athletes have now gained the opportunity to benefit financially from their notoriety by adopting an influencer role. The purpose of this manuscript was to explore the conceptual and theoretical shifts resulting from the introduction of the influencer role, considering the existing literature on athlete–student role theory. By achieving harmony between the athlete, student, and influencer roles, athletes should produce the most significant gains in each area, including academic performance, athletic achievement, and monetary benefit. However, greater psychological and sociological consequences may emerge for athletes if the influencer role further complicates the conflict between their athlete and student roles.

BACKGROUND: Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. METHODS: We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa, over a 30-year period between 1985 and 2015. We assessed the relationship between demographic, clinical, laboratory and neuro-imaging characteristics, and cognitive impairment at the conclusion of anti-tuberculous treatment. Poor outcome was defined as moderate-to severe cognitive impairment. RESULTS: A total of 327 TBM patients were included, 71 (21.7%) suffered a poor outcome. Multivariate analysis revealed that decreased level of consciousness (adjusted OR (aOR): 4.68; 95%CI: 2.43-13.88; p=0.005), brainstem dysfunction (aOR: 3.20; 95%CI: 1.70-6.00; p

Point-of-care ultrasound (US) has been suggested as the primary imaging in evaluating patients with suspected diverticulitis. Discrimination between simple and complicated diverticulitis may help to expedite emergent surgical consults and determine the risk of complications. This study aimed to: (1) determine the accuracy of an US protocol (TICS) for diagnosing diverticulitis in the emergency department (ED) setting and (2) assess the ability of TICS to distinguish between simple and complicated diverticulitis.Patients with clinically suspected diverticulitis who underwent a diagnostic computed tomography (CT) scan were identified prospectively in the ED. Emergency US faculty and fellows blinded to the CT results performed and interpreted US scans. The presence of simple or complicated diverticulitis was recorded after each US evaluation. The diagnostic ability of the US was compared to CT as the criterion standard. Modified Hinchey classification was used to distinguish between simple and complicated diverticulitis.A total of 149 patients (55% female, mean ± SD age 58 ± 16 years) were enrolled and included in the final analyses. Diverticulitis was the final diagnosis in 75 of 149 patients (50.3%), of whom 53 had simple diverticulitis and 22 had perforated diverticulitis (29.4%). TICS protocol's test characteristics for simple diverticulitis include a sensitivity of 95% (95% confidence interval [CI] 87%-99%), specificity of 76% (95% CI 65%-86%), positive predictive value of 80% (95% CI 71%-88%), and negative predictive value of 93% (95% CI 84%-98%). TICS protocol correctly identified 12 of 22 patients with complicated diverticulitis (sensitivity 55% [95% CI 32%-76%]) and specificity was 96% (95% CI 91%-99%). Eight of 10 missed diagnoses of complicated diverticulitis were identified as simple diverticulitis, and two were recorded as negative.In ED patients with suspected diverticulitis, US demonstrated high accuracy in ruling out or diagnosing diverticulitis, but its reliability in differentiating complicated from simple diverticulitis is unsatisfactory.

von Willebrand factor (VWF) is a multimeric blood protein that acts as a mechanical probe, responding to changes in flow to initiate platelet plug formation. Previously, our laboratory tests had shown that using single-molecule imaging that shear stress can extend surface-tethered VWF, but paradoxically, we found that the required shear stress was higher than reported for free-in-flow VWF, an observation inconsistent with basic physical principles. To resolve this inconsistency critical to VWF’s molecular mechanism, we measured free-VWF extension in shear flow using pulsed laser stroboscopic imaging of single molecules. Here, laser pulses of different durations are used to capture multiple images of the same molecule within each frame, enabling accurate length measurements in the presence of motion blur. At high shear stresses, we observed a mean shift in VWF extension of

In this paper, the thesis is put forward that selective outcome incentives for party membership gain relevance over time. Two possible mechanisms are identified as the cause of this increase in importance: a supply-side mechanism based on processes of societal change that took place through generational succession and a demand-side mechanism focusing on shifts in the self-image and organizational structure of political parties. The supply-side mechanism should lead to changes in the motives of potential members, whereas the demand-side mechanism alters the incentives potential and current members are exposed to.The empirical analyses are based on the German Party Membership Studies of 1998, 2009 and 2017. These three studies are nationwide representative surveys of the members of the following six parties: Christian Democratic Union (CDU), Christian Social Union (CSU), Social Democratic Party of Germany (SPD), Free Democratic Party (FDP), Alliance90/The Greens (Bündnis90/Die Grünen), and The Left (Die Linke). Within the German Party Membership Studies, both the motives for joining the party and the current membership motives are surveyed.Empirically, it is shown that there is indeed an increase in the importance of selective outcome membership motives over the period under study. The mechanisms behind this increase in importance are investigated using multivariate Age-Period-Cohort (APC) models based on the cumulated data of the German Party Membership Studies. These analyses are based on a total of nearly 30,000 cases. The results of the APC analyses are largely consistent with the supply-side explanation of the increased importance of selective outcome motives for party entry and membership. The demand-side explanation is only partially confirmed.