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In modern manufacturing the ability of retracing produced components is crucial for quality management and process optimization. Tracking is essential, especially for analyzing the influence of the production parameters on the final quality of the castings. In the iron foundry industry, common marking methods, such as a datamatrix code, cannot be used due to harsh environmental conditions and the rough surface of the cast parts. This work presents a new coding and reading system that guarantees unique marking in the casting process.The coding is built up over several beveled pins and is read out using an optical 2D handheld scanner. With a deep convolutional neural network approach of object detection and classification, a stable image processing algorithm is presented. With a first prototype a reading accuracy of 99.86% for each pin was achieved with an average scanning time of 0.43 s. The presented code is compatible with existing foundry processes, while the handheld scanner is intuitive and reliable. This allows immediate benefits for process optimization.

Demokratie muss gelernt und gelebt werden – ein idealer Ort dafür ist die Schule. Das vorliegende Buch zeigt, wo Schülerinnen und Schüler in Deutschland, Österreich und der Schweiz in ihren Schulen mitbestimmen können und wie sie hierbei Toleranz, Empathie und Selbstwirksamkeit erlernen. Die Studie macht deutlich, dass Mitbestimmung in der Regel außerhalb des Unterrichts stattfindet, obwohl für junge Menschen gerade eine stärkere Beteiligung an Unterrichtsthemen besonders interessant ist. Demokratie muss gelernt und gelebt werden – ein idealer Ort dafür ist die Schule. Das vorliegende Buch zeigt, wo Schülerinnen und Schüler in Deutschland, Österreich und der Schweiz in ihren Schulen mitbestimmen können und wie sie hierbei Toleranz, Empathie und Selbstwirksamkeit erlernen. Die Studie macht deutlich, dass Mitbestimmung in der Regel außerhalb des Unterrichts stattfindet, obwohl für junge Menschen gerade eine stärkere Beteiligung an Unterrichtsthemen besonders interessant ist.

The introductory chapter begins by clarifying the rationale that led the editors to delve into this project despite the many challenges in this field of study. First, we outline the rationale that preceded our journey, while explaining the gap in the academic literature in this field. Thereafter, we address each of the four parts of this book. The first part deals with immigrant and immigrant-origin teachers. It reviews the social and linguistic challenges they face in geopolitical contexts in Israel, Europe, and the USA. The second part reviews the experiences of indigenous teachers as minorities in multilingual and bilingual schools. The third focuses on international minority teacher educators, and examines the pedagogical and cultural challenges they face as educators, instructors, and supervisors of pre-service teachers. The fourth and final part showcases ethnic minority teachers integrated into educational frameworks around the globe, highlighting the challenges and benefits involved. We conclude this chapter by presenting the potential contributions of the empirical evidence contained in this open-access book to the growing theoretical and practical understanding of the potential benefits and risks involved in these processes.

Switzerland is a country with a long immigration history. Today, 27% of all pupils in compulsory education are foreign nationals (Federal Statistical Office (FSO) Switzerland, Obligatorische Schule: Lernende nach Grossregion, Schulkanton, Bildungstyp und Staatsangehörigkeit (je-d-15.02.01.05). Retrieved from https://www.bfs.admin.ch/bfs/de/home/statistiken/bildung-wissenschaft/personen-ausbildung/obligatorische-schule.assetdetail.11787900.html, 2020). On the other hand, teachers of immigrant background constitute a small minority even though the demand for teachers is high, with secure jobs that pay well. Moreover, there is a debate on the question whether teachers with an immigrant background are especially qualified for teaching culturally diverse classes. Given that persons with an immigrant background tend to aspire to higher educational and occupational goals than non-immigrant individuals (Van De Werfhorst & Van Tubergen, Ethnicities 7(3):416–444, 2007), the question arises why individuals with an immigrant background do not choose to become teachers more often.In light of this question, we provide an overview of studies from Switzerland and examine transitions of individuals into and out of Universities of Teacher Education in Switzerland as well as studies concerning active teachers.We will discuss current research evidence, that suggests that social background as well as motivations for choosing the fields of study (which usually play a significant role in explaining differing educational decisions) do not provide an explanation for the low enrolment rate into teacher education among students with immigrant background. Evidence indicates that dichotomizing into immigrant and non-immigrant might conceal differences in attitudes which particularly those from stigmatized cultural backgrounds face. These findings are highlighted by empirical insights on practicing teachers who experience a lack of recognition and who develop a range of strategies in response to these experiences.

Under the impression of changing rainfall patterns, agriculture in Germany faces increasing drought stress problems and water saving irrigation is gaining importance in the agricultural practice. Porous pipes for subsurface irrigation are an innovative method which is promoted as a water-efficient way to apply irrigation water. In the present study “Ecotubes” porous pipe irrigation was used for irrigation of “Lollo Bionda” lettuce at the University of Weihenstephan-Triesdorf in Southern Germany and compared to state-of-the art drip irrigation both at surface and sub-surface installation. Four treatments were compared during three experimental cycles “summer”, “late summer” and “autumn”: (a) drip irrigation in standard surface installation (control), (b) sub-surface drip irrigation, (c) porous pipes at standard operation and (d) porous pipes at very low pressure. The treatments were compared in terms of crop development, irrigation water applied, yield and water use efficiency (WUE). The highest yields were observed at low pressure irrigation with porous pipes (39.4 t/ha) followed by subsurface drip irrigation (36 t/ha). However, it was shown that the total amount of irrigation water applied, rather than the irrigation method determined the overall yield level. Subsurface irrigation methods had the highest WUE with 50.5 and 49.6 kg/m3 for porous pipes and subsurface drip irrigation, respectively. The study shows that subsurface micro irrigation systems are good for water saving horticultural production in Germany. The use of porous pipes is a good option for subsurface irrigation depending on the technological development in terms of installation and recovery, and the durability of the material.

Agalsidase alfa; Cardiovascular outcomes; Renal outcomes Agalsidasa alfa; Resultados cardiovasculares; Resultados renales Agalsidasa alfa; Resultats cardiovasculars; Resultats renals Background Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the effects of treatment on large patient populations with rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of affected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS studies have made in understanding FD. Results FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confirmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been published in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term effectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its effects on morbidity and mortality, as well as the benefits of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agalsidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specific populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies. Conclusion FOS over the last 20 years has substantially increased the scientific knowledge around improved patient management of FD and continues to expand our understanding of this rare disease. FOS is funded by Takeda Pharmaceuticals International AG, which also assisted in analyzing the data and preparing the manuscript. Takeda Development Center Americas, Inc. provided funding to Excel Medical Affairs for support in writing and editing this manuscript.

Children’s hospitals are discharging patients to home with increasingly complex outpatient needs, making safe transitions of care (ToCs) of vital importance. Our study involved a survey of both outpatient providers and pediatric hospitalists associated with our medical center to better describe providers’ views on the ToC process. The survey included questions assessing views on patient care responsibilities, resource availability, our hospitalist-run postdischarge clinic (PDC), and comfort with telemedicine. Our hospitalists generally believed that primary care providers (PCPs) did not have adequate access to important ToC elements, whereas PCPs felt their access was adequate. Both provider types felt it was the inpatient team’s responsibility to manage patient events between discharge and PCP follow-up and that a hospitalist-run PDC may reduce interim emergency room visits. This study challenges perceptions about the ToC process in children and describes a generalizable approach to assessing provider perceptions surrounding the ToC within individual health systems.

Gangliosidoses are a group of inherited neurogenetic autosomal recessive lysosomal storage disorders usually presenting with progressive macrocephaly, developmental delay, and regression, leading to significant morbidity and premature death. A quantitative definition of the natural history would support and enable clinical development of specific therapies.Single disease registry of 8 gangliosidoses (NCT04624789). Cross-sectional analysis of baseline data in N = 26 patients. Primary end point: disease severity assessed by the 8-in-1 score. Secondary end points: first neurologic sign or symptom observed (1) by parents and (2) by physicians, diagnostic delay, as well as phenotypical characterization. Tertiary end points: neurologic outcomes (development, ataxia, dexterity) and disability.The 8-in-1 score quantitatively captured severity of disease. Parents recognized initial manifestations (startle reactions) earlier than physicians (motor developmental delay and hypotonia). Median diagnostic delay was 3.16 (interquartile range 0.69-6.25) years. In total, 8 patients presented with late-infantile phenotypes.Data in this registry raise awareness of these rare and fatal conditions to accelerate diagnosis, inform counseling of afflicted families, define quantitative end points for clinical trials, and can serve as historical controls for future therapeutic studies. We provide further insight into the rare late-infantile phenotype for G

PurposeGangliosidoses are a group of inherited neurogenetic autosomal recessive lysosomal storage disorders usually presenting with progressive macrocephaly, developmental delay and regression, leading to significant morbidity, and premature death. A quantitative definition of the natural history would support and enable clinical development of specific therapies.MethodsSingle disease registry of eight gangliosidoses (NCT04624789).Cross-sectional analysis of baseline data in N= 26 patients.Primary endpoint: disease severity assessed by the 8-in-1 score.Secondary endpoints: first neurological sign or symptom observed a. by parents and b. by physicians, diagnostic delay, as well as phenotypical characterization.Tertiary endpoints: Neurological outcomes (development, ataxia, dexterity) and disability.ResultsThe 8-in-1 score quantitatively captured severity of disease. Parents recognized initial manifestations (startle reactions) earlier than physicians (motor developmental delay and hypotonia). Median diagnostic delay was 3.16 [IQR 0.69 … 6.25] years. Eight patients presented with late-infantile phenotypes.ConclusionData in this registry raise awareness of these rare and fatal conditions in order to accelerate diagnosis, inform counselling of afflicted families, define quantitative endpoints for clinical trials, and can serve as historical controls for future therapeutic studies. The characterization of a late-infantile phenotype is novel. Longitudinal follow-up is planned.

Introduction To determine the psychosocial effects of a facial skeletal mal-relationship with its subsequent surgical correction in a group of patients treated using surgical orthodontics compared with a matched group of nontreated controls. Methods This study was approved by The Ohio State University Institutional Review Board. Subjects were patients presenting with facial skeletal mal-relationships whose proposed treatment plans included orthognathic surgery. This study used valid and reliable questionnaires: Orthognathic Quality of Life Questionnaire (OQLQ), Beck Depression Inventory II (Children's Depression Inventory – 2), Satisfaction with Life Scale, and State Trait Anxiety Inventory (State Trait Anxiety Inventory for Children), administered at 3 different stages of treatment (time 1 = initial pretreatment, time 2 = before oral surgery, and time 3 = at completion of treatment). Matched controls recruited at each time point completed the same questionnaires. Results A total of 267 subjects were recruited to participate in this study. There were no significant differences between treatment and control groups in age, sex, education level, or employment status at any of the 3 time points. The randomization test was used to compare values for all outcome variables between groups at the 3 stages of treatment. For the pretreatment period, T1, there were significant differences between patients and controls in domains 1 (P = 0.0126), 2 (P = 0.0000), and 3 (P = 0.0000) of the OQLQ (social aspects, facial esthetics, and oral function, respectively) as well as total OQLQ (P = 0.0000). For the presurgery period, T2, there were significant differences between patients and controls in domains 2 (P = 0.0136) and 3 (P = 0.0001) of the OQLQ (facial esthetics and oral function) as well as total OQLQ (P = 0.0291). Finally, for the posttreatment period, T3, there was a significant difference between patients and controls only in domain 3 (P = 0.0196) of the OQLQ (oral function). Conclusions The psychosocial profile of patients with a facial skeletal mal-relationship does not differ from the general population in depression, anxiety, and overall satisfaction with life. However, these patients do report a reduced quality of life based on condition-specific measures in social aspects, facial esthetics, and oral function. Concerns about oral function remain even up to 2 years after treatment is completed.

DNA double-strand breaks in cells of radionuclide-treated patients are quantifiable by immunofluorescence microscopy, using phosphorylation of histone-variant H2AX (γ-H2AX) to mark radiation-induced foci (RIFs). Using this method, we compared excess RIFs side by side in recipients of 177Lu-DOTATOC or 177Lu-prostate specific membrane antigen-617 (PSMA) radioligands. We also examined relations between blood dose and dose rate, RIFs, and platelet counts. Methods: Venous blood samples were obtained from 48 patients subjected to 177Lu-labeled radioligand therapy (177Lu-DOTATOC, 26; 177Lu-PSMA, 22) to quantify blood lymphocyte RIFs and blood activity concentrations at various time points, including baseline (before injection) and postinjection readings (5 min, 30 min, 4 h, 24 h, 48 h, and 72 h). Absorbed doses and dose rates to blood were derived from sequentially assessed blood activity concentrations and γ-camera imaging. Platelet levels in routine blood tests were monitored for 3 d after injection to assess responses. Results: RIF counts averaged 0.25 ± 0.15 at baseline. Postinjection RIF counts were significantly higher than baseline values, peaking at 5 min (average, 3.93 ± 2.51 min) and declining thereafter. Compared with RIF counts of 177Lu-DOTATOC, those of 177Lu-PSMA were significantly higher at 5 min after injection and significantly lower at 72 h after injection. These differences could not be fully explained by blood doses and dose rates, which were significantly higher for 177Lu-PSMA than for 177Lu-DOTATOC treatment at every time point. RIF counts overall correlated with dose rates across all time points (Pearson r = 0.78; P < 0.01) and with absorbed dose until 4 h after injection only (Pearson r = 0.42; P < 0.01). Declines in platelet concentration correlated significantly with RIFs at 72 h after injection (Pearson r = -0.34; P < 0.05). Conclusion: Although values generated by the currently used blood dosimetry model correlated with RIF counts, the difference observed in 177Lu-DOTATOC and 177Lu-PSMA treatment groups was unexplained. Significantly more RIFs were found in 177Lu-DOTATOC recipients by comparison, despite lower dose rates and blood doses, exposing a potential limitation.

Detailed knowledge about radiation exposure is crucial for radiology professionals. The conventional calculation of effective dose (ED) for computed tomography (CT) is based on dose length product (DLP) and population-based conversion factors (k). This is often imprecise and unable to consider individual patient characteristics. We sought to provide more precise and individual radiation exposure calculation using image based Monte Carlo simulations (MC) in a heterogeneous patient collective and to compare it to phantom based MC provided from the National Cancer Institute (NCI) as academic reference. Dose distributions were simulated for 22 patients after whole-body CT during Positron Emission Tomography-CT. Based on MC we calculated individual Lifetime Attributable Risk (LAR) and Excess Relative Risk (ERR) of cancer mortality. EDMC was compared to EDDLP and EDNCI. EDDLP (13.2 ± 4.5 mSv) was higher compared to EDNCI (9.8 ± 2.1 mSv) and EDMC (11.6 ± 1.5 mSv). Relative individual differences were up to −48% for EDMC and −44% for EDNCI compared to EDDLP. Matching pair analysis illustrates that young age and gender are affecting LAR and ERR significantly. Because of these uncertainties in radiation dose assessment automated individual dose and risk estimation would be desirable for dose monitoring in the future.

Non-alcoholic steatohepatitis (NASH) is a rapidly growing liver disease. The chemoattractant chemerin is abundant in hepatocytes, and hepatocyte expressed prochemerin protected from NASH. Prochemerin is inactive and different active isoforms have been described. Here, the effect of hepatocyte expressed muChem-156, a highly active murine chemerin isoform, was studied in the methionine–choline deficient dietary model of NASH. Mice overexpressing muChem-156 had higher hepatic chemerin protein. Serum chemerin levels and the capability of serum to activate the chemerin receptors was unchanged showing that the liver did not release active chemerin. Notably, activation of the chemerin receptors by hepatic vein blood did not increase in parallel to total chemerin protein in patients with liver cirrhosis. In experimental NASH, muChem-156 had no effect on liver lipids. Accordingly, overexpression of active chemerin in hepatocytes or treatment of hepatocytes with recombinant chemerin did not affect cellular triglyceride and cholesterol levels. Importantly, overexpression of muChem-156 in the murine liver did not change the hepatic expression of inflammatory and profibrotic genes. The downstream targets of chemerin such as p38 kinase were neither activated in the liver of muChem-156 producing mice nor in HepG2, Huh7 and Hepa1-6 cells overexpressing this isoform. Recombinant chemerin had no effect on global gene expression of primary human hepatocytes and hepatic stellate cells within 24 h of incubation. Phosphorylation of p38 kinase was, however, increased upon short-time incubation of HepG2 cells with chemerin. These findings show that muChem-156 overexpression in hepatocytes does not protect from liver steatosis and inflammation.

Introduction The reliability of the cervical vertebral maturation (CVM) method has been questioned. The objective of this research was to evaluate the diagnostic reliability of the CVM method to diagnose the mandibular growth spurt using longitudinal records from an alternative database (Iowa Facial Growth Study [IFGS]) using established diagnostic testing methods. Methods Cephalometric films from 43 subjects (males = 20, females = 23) with Class I or Class II skeletal pattern from the IFGS were scanned, digitized, and adjusted for magnification. At least 5 consecutive, annual films were digitized. For each subject, mandibular length (Co-Gn) was measured for each film, and the growth increment between films was calculated. The largest growth increment was the growth spurt. For each subject, the film displaying CVM stage 3 was identified by a blinded examiner viewing the films in random order. Interrater and intrarater repeatability for Co-Gn (intraclass correlation) and CVM staging (weighted kappa) were calculated. Diagnostic tests, including sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were carried out. The present data were compared with data previously derived from samples of the University of Michigan, Oregon, and Burlington Growth studies (UMGS, OGS, and BGS, respectively). A multilevel logistic regression analysis was also run with the mandibular growth peak as the response variable. Results Interrater repeatability for mandibular measurements (intraclass correlation coefficient [ICC] = 0.91) and CVM staging (k = 0.88) were excellent. Intrarater repeatability for mandibular measurements (ICC = 0.98) and CVM staging (kw = 0.55) were excellent to moderate. The UMGS data demonstrated higher sensitivity with comparable specificity. Accuracy was largely similar. Their PPV and NPV had larger ranges. The OGS and BGS data, compared with the IFGS data, showed that our sensitivity and PPVs were higher, that their specificity was higher, and that the NPV and accuracy were very similar. The regression analysis was applied to age groups 10-11 years through 13-14 years. Only chronological age was significant (P = 0.04). Conclusions Agreement between CVM stage 3 and the maximum mandibular growth spurt is inconsistent. The diagnostic capability of CVM for the mandibular growth spurt is questionable.

One of the potential applications of ring-shaped, single grain RE-Ba-Cu-O bulk superconductors is in desktop magnetic resonance imaging (MRI) and nuclear magnetic resonance (NMR) systems as an alternative to conventional permanent magnets. The higher magnetic field available from magnetized bulk superconductors could significantly improve the performance of such systems, as well as reduce their size and increase portability. The pulsed field magnetization (PFM) method provides a fast, compact and cost-effective method for magnetizing these materials as trapped field magnets. However, bulk superconducting rings are very suscep-tible to thermomagnetic instabilities during the PFM process, and thus, to date, the reported trapped fields in ring bulks magnet-ized by PFM are less than 0.35 T at the centre of single rings. In this work, we demonstrate that the trapped field in a super-conducting ring bulk can be enhanced significantly by optimizing the waveform of the magnetizing pulse used in the PFM method. This optimization can be achieved easily by using an Insulated Gate Bipolar Transistor as a fast-switching device with a control-lable switching frequency in the pulse-generating electric circuit. Our findings represent a key step forward in utilizing bulk, sin-gle-grain superconducting rings magnetized by PFM in portable magnet systems.

Background Revisits within 30 days to an emergency department (ED), observation care unit, or inpatient setting following patient discharge continue to be a challenge, especially in urban settings. In addition to the consequences for the patient, these revisits have a negative impact on a health system’s finances in a value-based care or global budget environment. LifeBridge Health, a community health system in Maryland, United States, implemented an automated mobile patient engagement application as part of our enterprise-wide digital health strategy to improve patient engagement and reduce revisits to the ED. Objective The aim of this paper was to evaluate the effectiveness of a customized automated digital patient engagement application (GetWell Loop) to reduce 30-day revisits after home discharge from an ED. Methods The LifeBridge Health Innovation Department and ED staff from 2 participating health system hospitals collaborated with GetWellNetwork to customize their patient engagement application with automated check-in questions and other on-demand resources (eg, streaming content explaining aspects of self-care during COVID-19). An application link was emailed to adult patients discharged home from the ED. A study of ED visits for patients treated for general medicine and cardiology conditions between August 1, 2018, and July 31, 2019, was conducted using CRISP (Chesapeake Regional Information System for our Patients), Maryland’s state-designated health information exchange. We also used data within GetWell Loop (GetWellNetwork) to track patient activation and engagement. The primary outcome was the number of ED patients who experienced a 30-day revisit and who did or did not activate their GetWell Loop account. Secondary outcomes included the overall activation rate and the rate of engagement as measured by the number of logins, alerts, and comments generated by patients through the application. Bivariate analysis comparing outcomes among patients who activated the GetWell Loop application to patients who did not was conducted using the Fisher exact test. Multivariate logistic regression modeling with elastic net regularization was also performed to account for potential confounders and potential collinearity of covariates. Results During this 1-year study, 1062 (27.4%) of 3866 of all emergency patients treated for general medicine or cardiology conditions, who received an invite to use the digital application, activated their account. The patients discharged from the ED, who were treated for general medicine conditions (n=2087) and who activated their GetWell Loop account, experienced a 30-day revisit rate of 17.3% (n=101) compared with 24.6% (n=369) for those who did not activate their account (P Conclusions Our results suggest that a significant percentage of patients are willing to utilize a digital application following ED discharge to better engage in their own care, and that usage of such digital applications may significantly reduce 30-day revisit rates. LifeBridge Health’s experience demonstrates that health care systems can leverage automated mobile apps to improve patient engagement and successfully impact clinical outcomes at scale.

Farmers and consultants face an unmanageable amount of diverse knowledge and information for crop management decisions. To determine optimal actions, decision makers require knowledge-based support. In this way, decisions can be improved and heuristics can be replaced over time. The study presents a digital knowledge base with an integrated decision support system (DSS), using the example of nutrient supply, specifically nitrogen (N), fertilization. Therefore, the requirements of farmers and crop consultants for DSS to inform fertilization decisions for winter wheat (Triticum aestivum L.) were elaborated using surveys, expert interviews, and a prototype test. Semantic knowledge was enriched by expert knowledge and combined in a web application, the Crop Portal. To map regional and personal decision making patterns and experiences, the tacit knowledge on the complex advisory problem of N fertilization is made digitally usable. For this purpose, 16 fuzzy variables were specified and formalized. Individual decision trees and their interactions with an integrative knowledge base were used to multiply the consulting reach of experts. Using three consultants and nine model farms from different soil–climate areas in Germany, the Crop Portal was tested under practical conditions and the perceived pragmatic and hedonic quality of the system was evaluated using a standardized questionnaire. The field test showed that the variation in fertilizer recommendations from the ‘digital advisor twin’ ranged from 5 kg N ha−1 to 16 kg N ha−1 when compared with the decisions of the experts in the field. The study presents the participatory development and evaluation of a rule-based DSS prototype in agricultural practice.

The application of natural and nature‑based features (NNBF) has grown steadily over the past 20 years, supported by calls for innovation in flood risk management (FRM) and nature‑based solutions from many different perspectives and organizations. Technical advancements in support of NNBF are increasingly the subject of peer‑reviewed and other technical literature. A variety of guidance has been published by numerous organizations to inform program‑level action and technical practice for specific types of nature‑based solutions. This effort to develop international guidelines on the use of NNBF was motivated by the need for a comprehensive guide that draws directly on the growing body of knowledge and experience from around the world to inform the process of conceptualizing, planning, designing, engineering, constructing, and operating NNBF.

Our goal was to assess visual and quantitative aspects of multimodal skeletal SPECT/CT reconstructions (recon) in differentiating necrotic and healthy bone of patients with suspected MRONJ.Prior to surgery, 20 patients with suspected MRONJ underwent SPECT/CT of the jaw 3-4 hours after injection of Tc-99m-DPD (622±112.4 MBq). SPECT/CT data were reconstructed using the multimodal xSPECT Bone and xSPECT Quant algorithms as well as the OSEM-algorithm FLASH 3D. For analysis, we divided the jaw into 12 separate regions. Both xSPECT Bone and FLASH 3D datasets were scored on a four-point scale (VIS xSPECT; VIS F3D), based on the intensity of localized tracer uptake. In F3D and xSPECT Quant datasets, local tracer uptake of each region was recorded as semi-quantitative uptake ratio (SQR F3D) or SUVs, respectively. ROC analysis was performed. Postoperative histologic results served as gold standard.VIS F3D, VIS xSPECT and SQR F3D did not differ significantly in diagnostic accuracy (VIS xSPECT sensitivity=0.64; specificity=0.89). Of the quantitative parameters, SUVpeak yielded the best interobserver reproducibility. SUVpeak was 9.9±7.1 (95%CI: 7.84-11.95) in MRONJ regions, as opposed 3.6±1.8 (95% CI:3.36-3.88) elsewhere, with a cutpoint of 4.5 (sensitivity=0.83; specificity=0.80). Absolute quantitation significantly surpassed VIS and SQR (p0.05) in accuracy and interobserver agreement (SUVpeak: κ=0.92; VIS xSPECT: κ=0.61; SQR F3D κ=0.66).Absolute quantitation proved significantly more accurate than visual and semi-quantitative assessment in diagnosing MRONJ, with higher interobserver agreement.ZIEL: Ziel unserer Studie war es, dass Potenzial der quantitativen Auswertung von multimodalen SPECT/CT-Rekonstruktionen (Recon) zum Nachweis von Kiefernekrosen bei Patienten mit vermuteter MRONJ zu untersuchen.Präoperativ wurden 20 Patienten mit vermuteter MRONJ 3–4h nach Injektion von im Mittel 622±112,4MBq Tc-99m-DPD mittels SPECT/CT untersucht. Die Daten wurden sowohl mittels xSPECT Bone und xSPECT Quant als auch mittels des konventionellen OSEM-Algorithmus Flash3D (F3D) rekonstruiert. Zur Auswertung wurde der Kieferknochen in 12 Regionen unterteilt. Die xSPECT Bone und F3D Recon wurden hinsichtlich der Höhe des Uptakes mithilfe einer visuellen 4-Punkte-Skala (VIS xSPECT; VIS F3D) ausgewertet. Zusätzlich erfolgte eine VOI-basierte Bestimmung von semiquantitativen Ratios anhand der F3D Recon (SQR F3D) bzw. von SUVs anhand der xSPECT Quant Recon in den gleichen Regionen. Eine ROC-Analyse wurde durchgeführt. Das histologische Ergebnis diente als Goldstandard.VIS F3D, VIS xSPECT und SQR F3D zeigten keine signifikanten Unterschiede bei der Genauigkeit und Inter-Observer-Reliabilität (VIS F3D Sensitivität=0,62; Spezifität=0,88). Der SUVDie absolute Quantifizierung zeigt, bei höherer Inter-Observer-Reliabilität, im Vergleich zur visuellen und semiquantitativen Evaluation eine überlegene Genauigkeit beim Nachweis einer MRONJ.

Simple Summary There are differences and similarities when assessing the short-term therapeutic response of chemotherapy and chemotherapy plus immunotherapy using imaging techniques, which may be necessary to make treatment decisions in malignant head and neck tumors. After both chemo- and immunochemotherapy, remission becomes measurable in cross-sectional and metabolic diagnostics after only one cycle of therapy, with 18FDG-PET/CT predicting complete remission of tumor cells in a representative biopsy better than MRI/CT examination in both therapeutic modalities. While complete tumor remission is highly likely (88%) after immunochemotherapy in tumors with low residual activity (≤40% of initial SUV), this is less common after chemotherapy alone (65%). In metabolic nonresponse with more than 80% residual activity, the probability of complete remission nevertheless is low after chemotherapy alone (6%). After immunochemotherapy, these false nonresponders are common (35%), requiring additional diagnostics by deep biopsy. Cases of pseudoprogression with an increase of SUVmax of more than 125% of the baseline were not observed. Abstract Background: In head and neck cancer patients, parameters of metabolic and morphologic response of the tumor to single-cycle induction chemotherapy (IC) with docetaxel, cis- or carboplatin are used to decide the further course of treatment. This study investigated the effect of adding a double immune checkpoint blockade (DICB) of tremelimumab and durvalumab to IC on imaging parameters and their significance with regard to tumor cell remission. Methods: Response variables of 53 patients treated with IC+DICB (ICIT) were compared with those of 104 who received IC alone. Three weeks after one cycle, pathologic and, in some cases, clinical and endoscopic primary tumor responses were evaluated and correlated with a change in 18F-FDG PET and CT/MRI-based maximum-standardized uptake values (SUVmax) before (SUVmaxpre), after treatment (SUVmaxpost) and residually (resSUVmax in % of SUVmaxpre), and in maximum tumor diameter (Dmax) before (Dmaxpre) and after treatment (Dmaxpost) and residually (resD). Results: Reduction of SUVmax and Dmax occurred in both groups; values were SUVmaxpre: 14.4, SUVmaxpost: 6.6, Dmaxpre: 30 mm and Dmaxpost: 23 mm for ICIT versus SUVmaxpre: 16.5, SUVmaxpost: 6.4, Dmaxpre: 21 mm, and Dmaxpost: 16 mm for IC alone (all p < 0.05). ResSUVmax was the best predictor of complete response (IC: AUC: 0.77; ICIT: AUC: 0.76). Metabolic responders with resSUVmax ≤ 40% tended to have a higher rate of CR to ICIT (88%; n = 15/17) than to IC (65%; n = 30/46; p = 0.11). Of the metabolic nonresponders (resSUVmax > 80%), 33% (n = 5/15) achieved a clinical CR to ICIT versus 6% (n = 1/15) to IC (p = 0.01). Conclusions: ICIT and IC quickly induce a response and 18F-FDG PET is the more accurate modality for identifying complete remission. The rate of discrepant response, i.e., pCR with metabolic nonresponse after ICIT was >30%.

Purpose Following the publication of 5-year agalsidase alfa enzyme replacement therapy (ERT) outcomes data from the Fabry Outcome Survey (FOS), 10-year data were analyzed. Patients and methods FOS (ClinicalTrials.gov identifier: NCT03289065) data (April 2001 to August 2018) were retrospectively analyzed. Estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) were analyzed after treatment start (baseline) for patients with ≥3 measurements, including baseline and year 10. Results Median (range) age (years) of the evaluable treated renal cohort at treatment start was 48.8 (17.9-67.3) for females (n=62), 34.4 (18.0-66.8) for males (n=90). With eGFR ≥60 mL/min/1.73 m2 at baseline, mean (95% CI) rate of eGFR change (eGFR/year) over 10 years was relatively stable in females (n=52; -0.55 [-1.12, +0.01]) and slightly declined in males (n=79; -1.99 [-2.45, -1.54]). With impaired kidney function (eGFR 48 g/m2.7 in females, >50 g/m2.7 in males) at baseline, mean (95% CI) LVMI/year slightly increased over 10 years in females (n=18; +1.51 [+0.91, +2.12]) and males (n=14; +0.87 (+0.19, +1.55). Without LVH at baseline, mean (95% CI) LVMI/year was stable in females (n=16; +0.52 [-0.13, +1.17]) and males (n=21; +0.57 [+0.02, +1.13]) over 10 years. Conclusion Agalsidase alfa-treated patients with 10-year FOS data and preserved kidney function and/or normal LVMI at baseline remained largely stable; those with decreased kidney function or LVH at baseline experienced modest declines in renal function and/or increases in LVMI.

This paper provides an overview of the magnetic field measurement and subsequent electromagnetic re-modeling of the CLAS12 torus during the commissioning of the magnet in the fall of 2016. The CLAS12 detector in Hall B is part of the 12 GeV Accelerator Upgrade project at Jefferson Lab. The torus magnet allows precise determination of particle momenta within a cone ~ (5°-40°) in the forward direction. The ability to do this requires that we know the ∫B·dl of the torus to within an accuracy of 0.5% or better. To achieve this, an accurate model of the field along the particle path is required. The TOSCA code is used to generate a full three-dimensional (3-D) simulation of the magnetic envelope of the magnet as designed. Experimentally, the actual magnetic field within the magnet was surveyed to confirm the model design and to measure the deviation from the ideal case. The magnetic field deviations are attributed to manufacturing variability and assembly tolerances. A final model was created with allowances for these deviations guided by the survey data to create a more precise field integral model, which greatly improves the momentum resolution capability, allowing it to deliver the required specifications.

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016–2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label. Fifty patients (33 CML and 17 Ph+ ALL) were enrolled. Fifty-five percent of CML and 29% of Ph+ ALL patients had received ≥3 prior tyrosine kinase inhibitors (TKIs). Reasons for starting ponatinib were intolerance (40%), relapse or refractoriness (28%) to previous TKIs, progression (16%), or T315I mutation (16%). Median follow-up was 15 months for CML and 4.5 months for Ph+ ALL patients. Best response was a major molecular response in 58% of CML and 41% of Ph+ ALL patients. Of 20 patients who started ponatinib due to intolerance to previous TKIs, 9 (64%) CML and 4 (67%) Ph+ ALL achieved a major molecular response. Three-year estimates of overall survival were 85.3% and 85.6%, respectively, in CML and Ph+ ALL patients; estimated progression-free survival was 81.6% and 48.9%. Adverse reactions were reported in 34 patients (68%); rash (26%) and dry skin (10%) were most common. Reported cardiovascular adverse reactions included vascular stenosis (3), arterial hypertension (2), chest pain (1), palpitations (1), and vascular occlusion (1). This Belgian registry confirms results from the PACE clinical trial and supports routine ponatinib use in CML and Ph+ ALL patients who are resistant or intolerant to previous TKIs or with the T315I mutation. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04507-x.

Background The human immune system is comprised of a complex network of immune checkpoint receptors that are promising new immunotherapy targets for the treatment of a variety of cancers and autoimmune disorders. The Nobel prize for Medicine in 2018 was awarded for seminal studies on the role of immune checkpoint targets in T cell activation and furthermore, combining different strategies to release the brakes on the immune system with the aim of eliminating tumor cells even more efficiently. Immunotherapies designed to block co-inhibitory receptors (e.g. PD-1, CTLA-4, TIGIT) are showing unprecedented efficacy in the treatment of cancer. However, not all patients and tumor types respond to this approach. This has resulted in broadening of immunotherapy research programs to target additional co-inhibitory (e.g. LAG-3, TIM-3) and co-stimulatory (e.g. 4-1BB, GITR, OX40, ICOS) receptors individually and in combination. A major challenge in the development of antibody-based biologics is access to quantitative and reproducible functional bioassays. Existing methods rely on primary cells and measurement of complex functional endpoints. These assays are cumbersome, highly variable and fail to yield data required for drug development in a quality-controlled environment. Methods To address the need of access to a robust and reliable functional assay for immunotherapy drug development programs, we have developed a suite of cell-based functional bioassays to interrogate modulation of immune checkpoint receptors individually (e.g. PD-1, CTLA-4, LAG-3, TIM-3, GITR, 4-1BB,OX40, CD40) and in combination (e.g. PD-1+CTLA-4, PD-1+4-1BB). These assays consist of stable cell lines that express luciferase reporters driven by response elements under the precise control of mechanistically relevant intracellular signals. Thus, the bioassays reflect mechanisms of action for the drug candidates designed for each immune checkpoint receptor and demonstrate high specificity, sensitivity and reproducibility. Here we describe the application of MoA-based immune checkpoint receptor bioassays as tools for biologics drug discovery, development, potency and stability studies. Results We demonstrate that these bioassays measure response and inhibition with blocking drugs or potency changes from stressed samples. Conclusions In summary, these reporter-based bioassays provide valuable tools for the development, stability testing, and potency determination in the manufacture of biologics that are targeted to immune checkpoint.

Objectives (1) To assess the effectiveness of the Orthognathic Quality of Life Questionnaire (OQLQ) and the Child Oral Health Impact Profile (COHIP) to detect differences in Oral Health-Related Quality of Life (OHRQoL) between pediatric patients with dentofacial deformities and controls. (2) To assess for correlations between scores from the OQLQ and COHIP domains with the type and severity of the skeletal mal-relationship. (3) To assess if the COHIP and OQLQ were identifying unique or overlapping OHRQoL concerns. Materials and Methods Subjects were under age 18, presented with a dentofacial deformity, and completed both surveys. Matched controls completed the same. Severity for conditions was recorded via overjet, overbite, and ANB values and subjects were classified as skeletal Class I, II, or III. Results Enrollment yielded 30 subjects and 31 controls. For the OQLQ, significant differences between subjects and controls were found for the Facial Esthetics domain, Oral Function domain, and total score. For the COHIP, significant differences were found for the Social/Emotional Well-Being and Self-Image domains plus total score. There were no significant correlations between the severity of the condition as measured by overjet and reported OHRQoL for any domains. Conclusions The OQLQ and COHIP are effective at detecting significant OHRQoL differences between pediatric patients with dentofacial deformities and controls. Although there is some overlap in the results, the instruments appear to identify different OHRQoL concerns.

Measuring of the center of pressure (CoP) is one of the most frequently used quantitative methods for quantifying postural performance. The aim of the study is to describe differentiation criteria in the CoP-track for the clinical picture of chronic unspecific back pain. In this study, dynamic models loaded with multi-variable controls are used to determine whether biomechanical questions for upright posture can be answered. These models are particularly well suited for investigating the kinematics and the influence of the influencing disturbance variables. These investigations are extended by power density spectrum (PSD) analyses of CoP measurements on 590 subjects with and without chronic non-specific back pain. Pain patients show an average of 0.5 Nm2 more area under the spectrum than the pain-free reference group. In the power density spectrum different frequency ranges can be assigned to specific body oscillation. Among others, the frequency range between 0.5–0.8 Hz corresponds to the hip movement. In the range around 0.2 Hz, the movements are reflected in the upper body. Patients with back pain experience less activity in certain, individual areas.

First2 Network is an organization that focuses on underrepresented students in college. These underrepresented STEM students in First2 are first generation, persons of color, LGBTQIA+, Appalachian, low income, or financially disabled. First2 helps these students by increasing their likelihood of graduation by allowing students to do hands-on research with faculty, receive a stipend, and attend conferences at around the state. First2 also offers immersion programs throughout West Virginia. The immersive programs are available to high school seniors who plan on attending college and fit into one or more of the underrepresented groups. The immersive program places students on college campuses to conduct two-weeks of hands-on research and receive an educational stipend for their hard work. Upon completion of the immersive program students are eligible to become First2 Scholars. These scholars conduct research throughout the academic year, create lasting friendships, and attend scholarly conferences. The First2 initiative is beneficial for all underrepresented STEM students and a great opportunity.

448 Aim: PET/CT allows for accurate, post-therapeutic determination of the Y-90 distribution, which can be converted to maps of absorbed dose [1]. Yet, several parameters affect the accuracy of activity- and dose-maps. The aim of this work was to determine the effects of varying PET reconstruction parameters onto absorbed dose maps. Material and Methods: After SIRT, a PET/CT scan (Siemens Biograph mCT 40, one bed-position, 30 minutes duration) was carried out in 10 patients in order to determine Y-90-resin microsphere distribution. From reconstructed PET data, dose-maps where derived by convolution with pre-calculated dose-voxel-kernels. An MR image was co-registered to PET/CT data and manually segmented for healthy liver (HL) and tumor (TU) regions, for which dose-volume-histograms (DVH) were calculated. DVHs were compared for six different PET reconstruction settings. All reconstructions had in common that corrections for decay, photon attenuation and scatter, and random coincidences were applied. The varied parameters were number of iterations, amount of post-reconstruction Gaussian smoothing, and whether point-spread-function (Siemens TrueX) was modelled or time-of-flight (ToF) information was applied. Evaluated reconstruction settings were: A) No PSF, No ToF, 2 iterations (i), 12 subsets (s), 6mm Gaussian B) PSF, No ToF, 2i, 12s, 6mm C) PSF, ToF, 1i, 21s, 0mm D) PSF, ToF, 1i, 21s, 3mm E) PSF, ToF, 1i, 21s, 6mm F) PSF, ToF, 2i, 21s, 6mm Results: Reconstruction F) led to smallest deviations between injected and PET-derived activity (7.2±5.5%, ranging 0.5 - 18.8). For F), mean absorbed dose to HL was 26.8±9.2 Gy (15.3-40.1) and 81.8±48.2 Gy (29.2-157.5) for TU. Reconstructions A) and B) led to systematically lower (p

DNA double-strand breaks in cells of radionuclide-treated patients are quantifiable by immunofluorescence microscopy, using phosphorylation of histone-variant H2AX (γ-H2AX) to mark radiation-induced foci (RIFs). Using this method, we compared excess RIFs side by side in recipients of

In this article, we will review various aspects of long QT syndrome (LQTS) necessary for hospitalists who care for children, adolescents, and young adults who have known LQTS and also review presenting features that should make one consider LQTS as a cause of hospitalization. Pediatric hospitalists care for patients who have suffered near-drowning, unexplained motor vehicular accidents, brief resolved unexpected events, sudden infant death syndrome, recurrent miscarriages, syncope, or seizures. These common conditions can be clinical clues in patients harboring 1 of 16 LQTS genetic mutations. LQTS is commonly caused by a channelopathy that can cause sudden cardiac death. Over the years, guidelines on management and recommendations for sports participation have evolved with our understanding of the disease and the burden of arrhythmias manifested in the pediatric age group. This review will include the genetic causes of LQTS, clinical features, and important historical information to obtain when these presentations are encountered. We will review medical and surgical treatments available to patients with LQTS and long-term care recommendations and prognosis for those diagnosed with LQTS.