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In this mixed-methods quality improvement project, we implemented and evaluated sexual orientation and gender identity (SOGI) form rollout in the electronic medical record. Families in our gender diversity program completed a baseline survey in 2017 (55/328 responded) and follow-up in 2020 (180/721 responded) to evaluate the frequency of affirmed name and pronoun use in the hospital. Survey feedback informed system-wide inclusivity efforts and training. SOGI was implemented in 2020 after 1,662 providers completed an online training and 11,090 team members completed gender and sexual orientation inclusivity training. We recommend similar trainings for health systems utilizing SOGI.

Objective: To identify characteristics associated with bullying involvement in pediatric ADHD. Methods: Data from the 2016 to 2017 National Survey of Children’s Health for children aged 6 to 17 years with ADHD were evaluated to assess the association between parent-reported bullying victimization or perpetration and the following potential predictors: demographic characteristics, family factors, school factors, and child conditions/behaviors. Results: Among children with ADHD, 46.9% were bullying victims and 16.2% were perpetrators. Factors associated with victimization included having family financial strain, developmental delay or intellectual disability, friendship difficulties, and school reports about problems. Factors linked to perpetration included being male, receiving government assistance, lack of school engagement, school reports about problems, and having difficulties with friendships, staying calm, and arguing. Conclusions: Children with ADHD frequently were bullying victims and sometimes bullying perpetrators. Factors related to family financial strain, developmental disabilities, emotional regulation, peer relationships, and school functioning may help to identify risk for bullying and opportunities for anti-bullying interventions.

The present study investigated the effect of environmental temperature on the hand-feel perception of textiles. Participants were exposed to three different climate conditions (10 °C/20 °C/30 °C, RH 65 %) to simulate cool, mild, and warm environments. Hand-feel attributes, comfort, and preferences of a wide range of textiles were rated by the participants. Participants’ body responses to the different temperatures were controlled by monitoring participants’ aural temperature, mean skin temperature, hand temperature, tactile sensitivity, and environmental perception. Fabric weight was measured to monitor changes in textile properties induced by the different environmental conditions. The outcomes of the study suggest that the environmental temperature led to significant changes in participants’ aural temperature, mean skin temperature, hand temperature, tactile sensitivity, and environmental perception, affecting the hand-feel perception of the different textiles. Thus, the present study provides insight for practitioners to develop more comfortable textiles for specific environmental temperatures by establishing a basis for understanding how environmental temperature, body responses, and hand feel perception interact.

Aerosol jet printing is a noncontact, digital, additive manufacturing technique compatible with a wide variety of functional materials. Although promising, development of new materials and devices using this technique remains hindered by limited rational ink formulation, with most recent studies focused on device demonstration rather than foundational process science. In the present work, a systematic approach to formulating a polymer-stabilized graphene ink is reported, which considers the effect of solvent composition on dispersion, rheology, wetting, drying, and phase separation characteristics that drive process outcomes. It was found that a four-component solvent mixture composed of isobutyl acetate, diglyme, dihydrolevoglucosenone, and glycerol supported efficient ink atomization and controlled in-line drying to reduce overspray and wetting instabilities while maintaining high resolution and electrical conductivity, thus overcoming a trade-off in deposition rate and resolution common to aerosol jet printing. Biochemical sensors were printed for amperometric detection of the pesticide parathion, exhibiting a detection limit of 732 nM and a sensitivity of 34 nA μM

Zusammenfassung Bedeutung des Lungenkarzinoms Das Lungenkarzinom hat aufgrund seiner hohen Prävalenz und Mortalität enorme sozioökonomische Auswirkungen auf unsere Gesellschaft. Für das Jahr 2022 wurden ca. 59.700 Neuerkrankungen an Lungenkrebs prognostiziert. TNM-Schema zur Stadieneinteilung Die korrekte Ausbreitungsdiagnostik ist für die Therapieplanung, Prognoseabschätzung und zukünftige Analysen von grundlegender Bedeutung. Die Stadieneinteilung des Lungenkarzinoms erfolgt nach dem TNM-Schema der Union for International Cancer Control (UICC). Für die Stadien IIB–IIIC wird der Lymphknotenbefall zur Differenzierung herangezogen. Lymphknotenstationen beim Lungenkarzinom Die Kenntnis der intrathorakalen Lymphknotenstationen ist für die genaue Klassifikation von entscheidender Bedeutung, und deren Befall hat unmittelbare Auswirkungen auf die Therapie. Die International Association for the Study of Lung Cancer (IASLC) hat eine vereinheitlichte Lymphknotenkarte vorgeschlagen, die sich durch ihre exakten anatomischen Definitionen auszeichnet und in der aktuellen S3-Leitlinie für das Lungenkarzinom berücksichtigt wird. Der Lymphknotenbefall wird abhängig vom Ausmaß in N0–N3 stratifiziert. Je nach Lokalisation des Primärtumors lassen sich bevorzugte Metastasierungspfade nachweisen. Die Krankheitslast hat einen größeren Einfluss auf das Überleben als die Lokalisation der Metastasen. Ausbreitungsdiagnostik beim Lungenkarzinom Mit der Computertomographie (CT) kann die Operabilität des Primärtumors meistens sicher beurteilt werden. Invasive Verfahren zur Diagnosesicherung durch Probengewinnung sollten erst im Anschluss an nichtinvasive Diagnostik eingesetzt werden. Empfehlung für die Praxis In der aktuellen Leitlinie des Lungenkarzinoms wird bei allen Patienten mit nichtkleinzelligem Lungenkarzinom, die einer kurativen Resektion zugeführt werden, eine systematische Lymphknotenresektion empfohlen.

The Baltic Sea is still impacted by numerous pressures. More efforts are needed to reduce them for achieving healthy and resilient marine ecosystems and their sustainable uses. This can only be reached through the cooperation of Baltic Sea states and strong regional governance. The HELCOM Baltic Sea Action Plan 2021 is the promising instrument to implement these efforts for the Baltic Sea and to advance the global objectives of marine protection.

This chapter introduces the reader to the world of fiction and disinformation in early modern Europe. It starts by placing fiction and disinformation in the context of wider trends and developments, while also drawing a parallel between present practices and concerns and those of the early modern period (Section I). The chapter then surveys existing scholarship on these themes, highlighting the novelty of recent research and the transformative potential of interdisciplinary work (Section II). Finally, it sets out the approach and methodology which underpin the rest of volume (Section III). It is argued that fiction and disinformation need to be studied in tandem, and that their study should be guided by a combination of literary and historical approaches. This method is exemplified by the volume’s nine chapters. They all conduct close readings of falsehoods and fictional writings, examining their rhetorical and linguistic qualities, including matters such as style, narrative and genre; and they also uncover how fiction and disinformation brought about change in society and in the lives of the people who wrote them as much as those who read them. This makes the Supplement as a whole a methodological intervention, further bridging the gap between historical analysis and cultural criticism, and a contribution to the social and cultural history of early modernity.

Rapid, inexpensive, and easy-to-use coronavirus disease 2019 (COVID-19) home tests are key tools in addition to vaccines in the world wide fight to eliminate national and local shutdowns. However, currently available tests for SARS-CoV-2, the virus that causes COVID-19, are too expensive, painful, and irritating, or not sufficiently sensitive for routine, accurate home testing. Herein, we employ custom-formulated graphene inks and aerosol jet printing to create a rapid electrochemical immunosensor for direct detection of SARS-CoV-2 spike receptor-binding domain (RBD) in saliva samples acquired noninvasively. This sensor demonstrated limits of detection that are considerably lower than most commercial SARS-CoV-2 antigen tests (22.91 ± 4.72 pg ml−1 for spike RBD and 110.38 ± 9.00 pg ml−1 for spike S1) as well as fast response time (∼30 min), which was facilitated by the functionalization of printed graphene electrodes in a single-step with SARS-CoV-2 polyclonal antibody through the carbodiimide reaction without the need for nanoparticle functionalization or secondary antibody or metallic nanoparticle labels. This immunosensor presents a wide linear sensing range from 1 to 1000 ng ml−1 and does not react with other coexisting influenza viruses such as H1N1 hemagglutinin. By combining high-yield graphene ink synthesis, automated printing, high antigen selectivity, and rapid testing capability, this work offers a promising alternative to current SARS-CoV-2 antigen tests.

El primer aporte de la persona al mundo es la familia. La persona es en su intimidad pura coexistencia, es decir, abierta a ser con otros. Por esto, ella es desde dentro, un ser siempre acompañado. De algun modo, cada persona es por dentro familia; primero, con ella misma, porque se conoce como persona; segundo, porque se abre en aceptación íntima al Ser Originario; tercero, porque, desde su intimidad, se manifiesta a otras personas a quienes acepta y da. En la familia, la persona humana es aceptada, puede crecer desde adentro de sí junto con los otros que la acompañan y aprende a manifestar la radicalidad de su ‘ser’, su intimidad o sentido personal. A esto contribuye la educación propia de la intimidad familiar. En este estudio se pretende mostrar, mediante el método inductivo y con el apoyo de uno de los hallazgos radicales de la propuesta antropológica de L. Polo1, que la familia es el enclave íntimo en el que la persona crece y desde el cual, como sentido personal que es, se manifiesta. Con esto contribuye a configurar el ámbito social para hacerlo crecer en cohesión ética y en libertad. Este estudio amplía la reflexión de una previa investigación antropológica doctoral, denominada “En busca del sentido personal”, de mi autoría, que continúa los aportes de Polo en su antropología trascendental. (Tomado de la fuente) 1ra. edición

Este libro recoge una serie de artículos de investigación escritos por docentes y estudiantes que participan en los semilleros de investigación del Departamento de Humanidades de la Universidad Católica de Colombia. El centro temático de la obra son las reflexiones en relación con la persona, la intimidad y la sociedad. Cada capítulo brinda respuestas, desde un específico ámbito disciplinar, a través de una metodología cualitativa, al problema antropológico y ético fundamental del cultivo de la intimidad o interioridad personal y sus repercusiones en la vida social. En concreto, los textos estudian la familia como ámbito de intimidad con inspiración en la antropología trascendental de Leonardo Polo; enfocan su atención en el problema de reducir a la persona a productor y analizan la intimidad como apertura a lo espiritual, camino para recuperar una vida solidaria y fraterna; describen el papel de la intimidad entendida como gestora de grandes acontecimientos en el desarrollo histórico de Occidente, a partir del pensamiento de Agustín de Hipona; analizan el tema de la intimidad en el Magisterio de Pablo VI; abordan el concepto de intimidad familiar como lugar donde se recibe formación en valores humanos y religiosos; y presentan la relación que existe entre intimidad y desplazamiento. Con estas investigaciones se espera contribuir a la reflexión humanística alrededor del tema de la intimidad y estimular nuevas pautas de investigación que permitan entender mejor el difícil mundo en que vivimos. (Tomado de la fuente) 1ra. edición Prólogo Introducción La familia como ámbito de intimidad y fuente de sentido personal para la sociedad según la antropología trascendental de Leonardo Polo Intimidad y convivencia: repensar el valor del encuentro interhumano desde la intimidad La intimidad en la reflexión agustiniana y el devenir histórico El concepto de intimidad en el pontificado de Pablo VI (1963-1978) Historia íntima de una comunidad religiosa misionera: las hijas del Sagrado Corazón de Jesús de Italia en Brasil (1930-1934) Intimidad y desplazamiento forzado en Colombia. Un acercamiento a la persona

Deutschland mache keine gute Figur bei der Digitalisierung, ist zu hören und zu lesen. Doch das dürfte sich demnächst grundlegend ändern. Der Rollout intelligenter Messsysteme erhält vom Gesetzgeber Rückenwind. Und bei IoT-Anwendungen hat die Zukunft ohnehin schon begonnen. Die diesjährige E-world energy & water in Essen wird es zeigen: der Digitalisierungsexpress nimmt Fahrt auf, vom Smart Metering bis zur Smart City. Zu den Vorreitern zählen schon seit Jahren die Unternehmen der Zenner-Gruppe.

Predict hearing preservation after middle cranial fossa approach for vestibular schwannomas.Application of machine learning algorithms, including classification and regression trees and random forest models to observational data.Single-tertiary referral center.Patients (n = 144) with a previously untreated sporadic vestibular schwannoma who underwent microsurgical resection by middle cranial fossa approach between November 2017 and November 2021.Middle cranial fossa approach.Hearing preservation, defined by postoperative word recognition score of 50% or greater and pure tone average below 50 dB HL or less than 10% reduction in word recognition score. Model performance was evaluated with classification accuracy in an independent validation sample. Variable importance for the random forest model is reported according to entropy, a measure of mean decrease in model accuracy incurred by excluding each variable from the model.Hearing preservation was achieved in 60% of patients (86 of 144) overall. The classification and regression tree model identified preoperative pure tone average with a cut point of 30 dB HL, and more posterior tumor position to be the most important prognostic features for hearing preservation. Model accuracy was 0.68. The random forest model demonstrated perfect accuracy (1). Baseline pure tone average, word recognition score, and anteroposterior tumor position were among the most influential features for hearing preservation prediction.Machine learning algorithms have the potential for accurate prediction of hearing preservation rates after middle fossa approach for vestibular schwannomas at a single institution. These models have the capacity for continued refinement with ongoing addition of data.

Abstract. Introduction: Sports psychiatry, a field of psychiatry, is a young medical discipline. The aim of this study was to gauge opinions on the following: sports psychiatry as a specialized subdiscipline, its areas of activity among professionals, the desire for interdisciplinary and interprofessional cooperation, and the need for specific sports psychiatry training. Methods: An online survey was performed to assess the views on sports psychiatry of German-speaking professionals in Switzerland, Germany, and Austria in the field of sports psychiatry. Results: Data from 183 professionals were included in the analysis. Most participants classified sports psychiatry as a field of psychiatry (89%), followed by sports medicine (61%) and child and adolescent psychiatry (49%). Mental health and disorders in competitive and elite sport (94%), sport and exercise for the prevention of and as therapy for mental disorders (84%), and sport-specific mental health problems and disorders in popular sport (80%) were reported by all the participants as areas of activity within sports psychiatry. Most of the participants stated the importance of interdisciplinary and interprofessional collaboration with sports psychiatry’s areas of activity. While 84% of the participants emphasized the necessity for specific training in sports psychiatry, a different picture emerged as to whether such training should be independent or integrated with postgraduate training for psychiatric or sports medicine. Conclusion: The results provide insight into sports psychiatry and its areas of activity and should be used for, and integrated with, the further development of the field.

Motivation: Within the field of bio-implants one topic deals with the in-vitro production of 3D tissues from cell cultures. A major challenge in the cultivation of biopreparations is the imitation of the vascular system with its surrounding tissue. Additiv manufacturing of such vascularisation could be supported with an adequate template from high-resolution 3D radiographs. Goals: Evaluation of highresolution 3D-imaging methods and 3D-analysis approaches to extract the vascularisation from tissue samples. Methods: To provide such template, vascular structure of small tissues samples (partially treated with contrast medium) were recorded and compared using high-resolution CT and MRI imaging modalities. Optimal measurement parameters were selected for the acquisition of very small vessels. Interactive and semi-automated segmentation of the vessel system were investigated and compared. Results: MRI scans yield a higher contrast than CT scans, but are much slower. Duration of interactive segmentation ranges between 1 to 12 hours. Runtime of the (semi) automatic method was between 5 and 20 minutes, not counting manual adjustment of the parameters. Correlation between manual and automatic segmentation yield Hausdorff distances of 0.024 (CT) and 0.74 (MRI) and Dice coefficients of 0.7 (CT) and 0.39 (MRI). Conclusion: Both imaging methods are appropriate for high-resolution vessel detection and segmentation, nevertheless, MRI with no contrast agent seems preferable if the imaging time can be reduced.

This study evaluated the stability over time of prevalence estimates of mental disorders among school-aged children from the same community.We compared screening status and weighted prevalence of selected mental disorders from the two-stage school-based South Carolina Project to Learn About Youth-Mental Health (Time 1) and its replication study (Time 2) conducted between 2014 and 2017. During stage 1, two teacher screeners were used to group students into high or low risk for a mental disorder. During stage 2, parents of selected students completed a structured diagnostic interview to assess whether their child met criteria for specific disorders.For stage 1, 19.9% of students screened as high risk for a mental disorder at Time 2 compared to 17.8% at Time 1. Among students included at both timepoints, 9.1% screened as high risk at both timepoints while screening status changed for 20.7%. The overall prevalence of included mental disorders was approximately 18% at both time points There were no differences (P-values.05) in prevalence of individual mental disorders between Time 1 (range:0.3%-6.7%) and Time 2 (range:1.2%-7.7%).Study findings demonstrate that similar methodology yielded similar prevalence estimates of mental disorders and can inform community-level planning for improving mental health in children.

Background: Free-breathing 1H ventilation MRI shows promise but only single-center validation has yet been performed against methods which directly image lung ventilation in patients with cystic fibrosis (CF). Purpose: To investigate the relationship between 129Xe and 1H ventilation images using data acquired at two centers. Study type: Sequence comparison. Population: Center 1; 24 patients with CF (12 female) aged 9–47 years. Center 2; 7 patients with CF (6 female) aged 13–18 years, and 6 healthy controls (6 female) aged 21–31 years. Data were acquired in different patients at each center. Field Strength/Sequence: 1.5 T, 3D steady-state free precession and 2D spoiled gradient echo. Assessment: Subjects were scanned with 129Xe ventilation and 1H free-breathing MRI and performed pulmonary function tests. Ventilation defect percent (VDP) was calculated using linear binning and images were visually assessed by H.M., L.J.S., and G.J.C. (10, 5, and 8 years' experience). Statistical Tests: Correlations and linear regression analyses were performed between 129Xe VDP, 1H VDP, FEV1, and LCI. Bland–Altman analysis of 129Xe VDP and 1H VDP was carried out. Differences in metrics were assessed using one-way ANOVA or Kruskal–Wallis tests. Results: 129Xe VDP and 1H VDP correlated strongly with; each other (r = 0.84), FEV1 z-score (129Xe VDP r = −0.83, 1H VDP r = −0.80), and LCI (129Xe VDP r = 0.91, 1H VDP r = 0.82). Bland–Altman analysis of 129Xe VDP and 1H VDP from both centers had a bias of 0.07% and limits of agreement of −16.1% and 16.2%. Linear regression relationships of VDP with FEV1 were not significantly different between 129Xe and 1H VDP (P = 0.08), while 129Xe VDP had a stronger relationship with LCI than 1H VDP. Data Conclusion: 1H ventilation MRI shows large-scale agreement with 129Xe ventilation MRI in CF patients with established lung disease but may be less sensitive to subtle ventilation changes in patients with early-stage lung disease. Evidence Level: 2. Technical Efficacy: Stage 2.

Shape changes of epithelia during animal development, such as convergent extension, are achieved through concerted mechanical activity of individual cells. While much is known about the corresponding large scale tissue flow and its genetic drivers, the question of cell-scale coordination remains open. We propose that this coordination can be understood in terms of mechanical interactions and instantaneous force balance within the tissue. Using whole embryo imaging data for Drosophila gastrulation, we exploit the relation between balance of local cortical tension forces and cell geometry. This unveils how local positive feedback on active tension and passive global deformations account for coordinated cell rearrangements. We develop a model that bridges the cell and tissue scale dynamics and predicts the dependence of total tissue extension on initial anisotropy and hexagonal order of the cell packing. Our study provides general insight into the encoding of global tissue shape in local cell-scale activity. HIGHLIGHTS: Tissue flow is explained by controlled transformation of cortical tension balance. Positive tension feedback drives active cell intercalation. Coordination of cell intercalation requires order in local tension configurations. Tension dynamics model predicts total tissue shape change from initial cellular order.

Background Among adults with cancer, malnutrition is associated with decreased treatment completion, more treatment harms and use of healthcare, and worse short-term survival. To inform the National Institutes of Health Pathways to Prevention (P2P) workshop, Nutrition as Prevention for Improved Cancer Health Outcomes, this systematic review examined the evidence for the effectiveness of providing nutritional interventions before or during cancer therapy to improve outcomes of cancer treatment. Methods We identified randomized controlled trials (RCT) enrolling ≥50 participants published from 2000 through July 2022. We provide a detailed evidence map for included studies and grouped studies by broad intervention and cancer types. We conducted risk of bias and qualitative descriptions of outcomes for intervention and cancer types with a larger volume of literature. Results From 9,798 unique references, 206 RCT from 219 publications met inclusion criteria. Studies primarily focused on non-vitamin/mineral dietary supplements, nutrition support, and route or timing of inpatient nutrition interventions for gastrointestinal or head and neck cancers. Most studies evaluated changes in body weight/composition, adverse events from cancer treatment, length of hospital stay, or quality of life. Few studies were conducted within the U.S. Among intervention and cancer types with a high volume of literature (n = 114), 49% (n = 56) were assessed as high risk of bias. Higher quality studies (low- or medium risk-of-bias) reported mixed results on the effect of nutritional interventions across cancer and treatment-related outcomes. Conclusions Methodological limitations of nutritional intervention studies surrounding cancer treatment impair translation of findings into clinical practice or guidelines.

Background: The COVID-19 (C19) pandemic shocked primary care systems around the world. Those systems responded by supporting patients in the community, and acute care facilities in crisis. In Canada, the Patient Medical Home (PMH) is a widely adopted care model that aims to operationalize the tenets and principles of Primary Health Care (PHC) as developed since the Alma-Ata Declaration. This paper describes how personnel working in and with Primary Care Networks (PCNs) in Alberta, Canada deployed the PMH model and its underlying PHC principles to frame and respond to the C19 shock. Methods: Using purposive and snowball sampling techniques, we interviewed 57participants who worked in public health and primary care, including community-based family physicians. We used interpretive description to analyze the interviews. Results: PCN staff and physicians described how the PMH model was foundational to normal operations, and how C19 responses were framed by the patient-centric, team-delivered, and continuous care principles the model shares with PHC. Specifically, participants described ensuring access to care, addressing the social determinants of health, being patient centered, and redeploying and expanding PHC teams to accomplish these goals. Discussion: Delivering PHC through the PMH allowed physicians and allied health staff to deliver patient-centered, team-based, holistic bio-medical services to Albertans. In tailoring services to meet the specific social and health needs of the populations served by each PCN, healthcare providers were able to ensure relevant support remained available and accessible.

O artigo aborda a dicotomia como fundamento lógico da produção de alteridades constitutiva da modernidade. A partir de dois exemplos, nas artes visuais e na música, busca mostrar que a dicotomia operou igualmente como dispositivo narrativo e formal nessa produção de alteridades.

Das Polymyxin-Antibiotikum Colistin ist in Deutschland seit 2012 als (Last-Line-)Antibiotikum für die systemische Therapie schwerer Infektionen mit multiresistenten Erregern zugelassen. 2016 wurde erstmals das Plasmid-vermittelte Colistinresistenzgen mcr-1 bei Menschen und Nutztieren beschrieben. Somit ist eine horizontale und speziesübergreifende Übertragung von mcr-1 und mrc-2 denkbar und es wurden seitdem weltweit zahlreiche bakterielle Isolate von Mensch und Tier z. T. auch retrospektiv auf das Vor¬handensein dieser neuen Resistenzgene untersucht. Eine weite Verbreitung von mcr-1/-2 wurde bestätigt. Vor diesem Hintergrund führte das Niedersächsische Landesgesundheitsamt in Kooperation mit der Westfälischen Wilhelms-Universität Münster und dem Nieder¬sächsischen Landesamt für Verbraucherschutz und Lebensmittelsicherheit eine Studie zur Verbreitung der mcr-vermittelten Colistinresistenz auf putenhaltenden Betrieben in Niedersachsen durch. Im Epidemiologischen Bulletin 19/2023 werden die Ergebnisse zusammengefasst und diskutiert.

Importance There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, Setting, and Participants The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2. Interventions Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks. Main Outcomes and Measures The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George’s Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life). Results At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was –124.6 mL (95% CI, −178.0 to −71.2 mL) with 600 mg of ziritaxestat vs –147.3 mL (95% CI, −199.8 to −94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, −52.3 to 97.6 mL]), and –173.9 mL (95% CI, −225.7 to −122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, −26.7 mL [95% CI, −100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was –173.8 mL (95% CI, −209.2 to −138.4 mL) with 600 mg of ziritaxestat vs –176.6 mL (95% CI, −211.4 to −141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, −46.9 to 52.4 mL]) and –174.9 mL (95% CI, −209.5 to −140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, −47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo. Conclusions and Relevance Ziritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment. Trial Registration ClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444

In addition to vaccines, the World Health Organization sees novel medications as an urgent matter to fight the ongoing COVID-19 pandemic. One possible strategy is to identify target proteins, for which a perturbation by an existing compound is likely to benefit COVID-19 patients. In order to contribute to this effort, we present GuiltyTargets-COVID-19 (https://guiltytargets-covid.eu/), a machine learning supported web tool to identify novel candidate drug targets. Using six bulk and three single cell RNA-Seq datasets, together with a lung tissue specific protein-protein interaction network, we demonstrate that GuiltyTargets-COVID-19 is capable of (i) prioritizing meaningful target candidates and assessing their druggability, (ii) unraveling their linkage to known disease mechanisms, (iii) mapping ligands from the ChEMBL database to the identified targets, and (iv) pointing out potential side effects in the case that the mapped ligands correspond to approved drugs. Our example analyses identified 4 potential drug targets from the datasets: AKT3 from both the bulk and single cell RNA-Seq data as well as AKT2, MLKL, and MAPK11 in the single cell experiments. Altogether, we believe that our web tool will facilitate future target identification and drug development for COVID-19, notably in a cell type and tissue specific manner.

This Special Issue takes the pulse of the UN Commission on International Trade Law process on reforming investor-state dispute settlement (ISDS) at its midway point. It features contributions by members of the Academic Forum on ISDS, engaging with various topics on the negotiating table, as well as some that are off the table or hovering in-between. Together, these articles seek to address questions of design, dilemmas and discontent – especially how states negotiate the values and tradeoffs of reform, and engage (or not) with critics of the process. They do so from the perspectives of law, social science and public policy and they employ a range of methods, including computational approaches.