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BH3 mimetics are increasingly used as anti-cancer therapeutics either alone or in conjunction with other chemotherapies. However, mounting evidence has also demonstrated that BH3 mimetics modulate varied amounts of apoptotic signaling in healthy immune populations. In order to maximize their clinical potential, it will be essential to understand how BH3 mimetics affect discrete immune populations and to determine how BH3 mimetic pressure causes immune system adaptation. Here we focus on the BCL-2 specific inhibitor venetoclax (ABT-199) and its effects following short-term and long-term BCL-2 blockade on T cell subsets. Seven day “short-term” ex vivo and in vivo BCL-2 inhibition led to divergent cell death sensitivity patterns in CD8+ T cells, CD4+ T cells, and Tregs resulting in shifting of global T cell populations towards a more memory T cell state with increased expression of BCL-2, BCL-XL, and MCL-1. However, twenty-eight day “long-term” BCL-2 blockade following T cell-depleted bone marrow transplantation did not lead to changes in the global T cell landscape. Despite the lack of changes in T cell proportions, animals treated with venetoclax developed CD8+ and CD4+ T cells with high levels of BCL-2 and were more resistant to apoptotic stimuli following expansion post-transplant. Further, we demonstrate through RNA profiling that T cells adapt while under BCL-2 blockade post-transplant and develop a more activated genotype. Taken together, these data emphasize the importance of evaluating how BH3 mimetics affect the immune system in different treatment modalities and disease contexts and suggest that venetoclax should be further explored as an immunomodulatory compound.

Financial scarcity, both real and imagined, is associated with impaired executive functions and present-focused economic decisions. What is the mechanism that connects the lack of financial resources to these cognitive and behavioral effects? The present work will test the hypothesis that the experience of financial stress contributes to these deficits by reducing executive functions related to self-control and causing present-focused, real-world economic decisions. In a preliminary experiment (N = 215), we found support for the hypothesis that financial stress (as compared to social stress) causes a reduction in inhibitory control performance. In a registered study, we will recruit participants from diverse socioeconomic backgrounds and assess their inhibitory control performance before and after a financial stress manipulation, and assess their economic preferences via both a survey and real-world measure of temporal discounting. Similar results in the proposed study would provide evidence that financial stress can help explain SES-based differences in self-control.

Background (Es)ketamine and monoamine oxidase inhibitors (MAOIs), e.g., tranylcypromine, are therapeutic options for treatment-resistant major depression. Simultaneous administration is currently not recommended because of concern about hypertensive crises. Objective Our objective was to evaluate whether changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) during esketamine administration differed between patients who concomitantly received tranylcypromine and those who did not. Methods This was a retrospective cohort study utilizing cardiovascular monitoring data from inpatients treated for severe depression in unipolar, bipolar, and schizoaffective disorder. Primary outcomes were change in mean BP and HR during the first hour after intravenous or subcutaneous esketamine administration compared with baseline, controlled for confounders. Secondary analyses quantify differences in absolute BP during esketamine treatment and comparisons of BP peaks, temporal effects, and intraindividual comparisons before and after tranylcypromine initiation. Results Our analysis included 509 esketamine administrations in 43 patients, 14 of whom concomitantly received tranylcypromine. Controlling for creatinine and age, mean ± standard deviation (SD) BP changes were significantly increased by concomitant tranylcypromine treatment (ΔSBP: F[1,503] = 86.73, p

In Deutschland werden rund 3 % aller Neugeborenen nach einer Kinderwunschbehandlung geboren. Haufigste Methode der assistierten Reproduktion (assisted reproductive technique [ART]) ist die intrazytoplasmatische Spermieninjektion (intracytoplasmic sperm injection [ICSI]). Ob es gesundheitliche Benachteiligungen bei Kindern und Jugendlichen, die nach einer ICSI-Behandlung geboren wurden, gibt, wird kontrovers diskutiert. In der Deutschen ICSI-Langzeitstudie wurde eine Kohorte von Kindern, die nach einer ICSI-Behandlung in den Jahren 1998 bis 2000 geboren wurden, zu drei Untersuchungszeitpunkten hinsichtlich ihrer gesundheitlichen, psychischen und sozialen Entwicklung untersucht (ICSI-Studie I–III). Der Schwerpunkt der ersten Untersuchung war der Schwangerschafts- und Geburtsverlauf sowie die neonatale Gesundheit der Kinder. Im zweiten Untersuchungszeitraum (2004–2006) wurde die somatische und neurologische Entwicklung der Einlinge untersucht, wahrend 2015–2017 (dritter Untersuchungszeitraum) die kardiometabolische und endokrinologische Entwicklung der Jugendlichen sowie deren Lebensqualitat und soziale Entwicklung im Mittelpunkt standen. Insgesamt kann festgestellt werden, dass die physische und psychische Entwicklung der Kinder vergleichbar zu spontan konzipierten Gleichaltrigen verlauft. Die Fehlbildungsrate nach ICSI ist geringfugig erhoht und das Geburtsgewicht etwas niedriger als bei spontan konzipierten Kindern. Die Mehrlingsrate ist erhoht, was u. a. zu mehr Fruhgeburtlichkeit mit entsprechenden Folgen fuhrt. Unterschiede in den metabolischen Faktoren konnen auf ein erhohtes Risiko fur kardiovaskulare Erkrankungen im spateren Lebensverlauf hinweisen. Ob das Verfahren der ICSI zu klinisch relevanten kardiovaskularen Risiken fuhrt, muss in weiteren Studien untersucht werden.

Climate change is causing an intensification in tundra fires across the Arctic, including the unprecedented 2015 fires in the Yukon-Kuskokwim (YK) Delta. The YK Delta contains extensive surface waters (∼33% cover) and significant quantities of organic carbon, much of which is stored in vulnerable permafrost. Inland aquatic ecosystems act as hot-spots for landscape CO2 and CH4 emissions and likely represent a significant component of the Arctic carbon balance, yet aquatic fluxes of CO2 and CH4 are also some of the most uncertain. We measured dissolved CH4 and CO2 concentrations (n = 364), in surface waters from different types of waterbodies during summers from 2016 to 2019. We used Sentinel-2 multispectral imagery to classify landcover types and area burned in contributing watersheds. We develop a model using machine learning to assess how waterbody properties (size, shape, and landscape properties), environmental conditions (O2, temperature), and surface water chemistry (dissolved organic carbon composition, nutrient concentrations) help predict in situ observations of CH4 and CO2 concentrations across deltaic waterbodies. CO2 concentrations were negatively related to waterbody size and positively related to waterbody edge effects. CH4 concentrations were primarily related to organic matter quantity and composition. Waterbodies in burned watersheds appeared to be less carbon limited and had longer soil water residence times than in unburned watersheds. Our results illustrate the importance of small lakes for regional carbon emissions and demonstrate the need for a mechanistic understanding of the drivers of greenhouse gasses in small waterbodies.

The nucleation and growth of calcium–silicate–hydrate (C–S–H) is of fundamental importance for the strength development and durability of the concrete. However, the nucleation process of C–S–H is still not fully understood. The present work investigates how C–S–H nucleates by analyzing the aqueous phase of hydrating tricalcium silicate (C3S) by applying inductively coupled plasma-optical emission spectroscopy as well as analytical ultracentrifugation. The results show that the C–S–H formation follows non-classical nucleation pathways associated with the formation of prenucleation clusters (PNCs) of two types. Those PNCs are detected with high accuracy and reproducibility and are two species of the 10 in total, from which the ions (with associated water molecules) are the majority of the species. The evaluation of the density and molar mass of the species shows that the PNCs are much larger than ions, but the nucleation of C–S–H starts with the formation of liquid precursor C–S–H (droplets) with low density and high water content. The growth of these C–S–H droplets is associated with a release of water molecules and a reduction in size. The study gives experimental data on the size, density, molecular mass, and shape and outlines possible aggregation processes of the detected species.

Dupilumab has recently been approved by the Food and Drug Administration for use for treatment of moderate to severe atopic dermatitis in children aged 6 to 11 years. It presents a novel treatment option with a favorable safety profile for patients who are currently reliant on immunosuppressants, including cyclosporine A, methotrexate, and mycophenolate mofetil. Particularly during the current COVID-19 pandemic, immunosuppression should be avoided to retain intrinsic antiviral immunity. Transitioning to dupilumab should be executed strategically-tapering immunosuppressants and minimizing risk of flare by overlapping with the biologic. Herein, we use results of outcome measurements from LIBERTY AD ADOL and LIBERTY AD PEDS trials of dupilumab in adolescents aged 12 to 18 years and children aged 6 to 11 years, respectively, to propose a schematic for an 8-week transition between medications.

Purpose In uveal melanoma patients, liver metastases can be treated by hepatic artery infusion chemotherapy (HAIC). During this procedure, melphalan or, less frequently, fotemustine is infused into the hepatic artery or the hepatic lobe arteries in regularly repeated interventions to achieve local tumor control. The aim of this study was to investigate the radiation exposure of HAIC. Material and methods In this retrospective study, dose data from 841 procedures in 140 patients (mean age 65.3 ± 9.9 years, 74 female) who underwent HAIC between 06/2017 and 10/2021 at one of three different angiography systems were analyzed. Results In the overall population, dose area product (DAP) (median (IQR)) was 1773 cGy·cm2 (884–3688). DAP was significantly higher in the first intervention, where a complete diagnostic workup of the vasculature was performed, than in follow-up interventions: 5765 cGy·cm2 (3160–8804) versus 1502 cGy·cm2 (807–2712) (p 2 (633–2717), two positions 1985 cGy·cm2 (1118–4074), three positions 6407 cGy·cm2 (2616–11590) (p Conclusion In uveal melanoma patients with liver metastases undergoing HAIC, radiation exposure is significantly higher both at the first intervention compared to follow-up interventions, but also with increasing number of infusion positions. Level of evidence: 3

Background and Aims: Radioembolization (RE) has recently demonstrated a non-inferior survival outcome compared to systemic therapy for advanced hepatocellular carcinoma (HCC). Therefore, current guidelines recommend RE for patients with advanced HCC and preserved liver function who are unsuitable for transarterial chemoembolization (TACE) or systemic therapy. However, despite the excellent safety profile of RE, post-therapeutic hepatic decompensation remains a serious complication that is difficult to predicted by standard laboratory liver function parameters or imaging modalities. LiMAx® is a non-invasive test for liver function assessment, measuring the maximum metabolic capacity for 13C-Methacetin by the liver-specific enzyme CYP 450 1A2. Our study investigates the potential of LiMAx® for predicting post-interventional decompensation of liver function. Patients and methods: In total, 50 patients with HCC with or without liver cirrhosis and not amenable to TACE or systemic treatments were included in the study. For patients prospectively enrolled in our study, LiMAx® was carried out one day before RE (baseline) and 28 and 90 days after RE. Established liver function parameters were assessed at baseline, day 28, and day 90 after RE. The relationship between baseline LiMAx® and pre-and post-interventional liver function parameters, as well as the ability of LiMAx® to predict hepatic decompensation, were analyzed. Results: We observed a strong association between baseline LiMAx® and bilirubin, albumin, ALBI grade, and MELD score. Patients presenting with Child–Pugh score B 28 days after RE or with a deterioration in Child–Pugh score by at least one point had a significantly lower baseline LiMAx® compared to those with Child–Pugh score A or with stable Child–Pugh score. The ability of LiMAx® to predict hepatic decompensation after RE was determined using ROC curve analysis and was compared to MELD score and ALBI grade. LiMAx® achieved a substantial AUC of 0.8117, comparable to MELD score and ALBI grade. Conclusion: Patients with lower LiMAx® values at baseline have a significantly increased risk for hepatic decompensation after RE, despite being categorized as Child–Pugh A. Therefore, LiMAx® can be used as an additional tool to identify patients at high risk of post-interventional hepatic failure.

Poster-Abstract

The optimal treatment sequence of tyrosine kinase inhibitor (TKI)-based therapy in patients with hepatocellular carcinoma (HCC) remains unclear. Therefore, sequential systemic therapy after first-line therapy with sorafenib or lenvatinib was compared in a retrospective real-world cohort. In total, 164 patients with HCC were included. Child B cirrhosis was present in 26 patients (16.5%), whereas 132 patients (83.5%) had preserved liver function. In total, 72 patients (44%) discontinued systemic therapy after first-line therapy while 51 (31%) and 31 (19%) patients received 2 or more treatment lines. Most notably, median overall survival (mOS) was influenced by liver functional status and patient performance status at the beginning of first-line therapy. Patients receiving a sequential therapy regimen had significantly longer mOS compared to patients that discontinued systemic therapy after omitting first-line treatment. The choice of the initial TKI did not impact mOS. A clear deterioration of liver function could be observed during the course of TKI-based treatment.

Background/aim 18 kDa Translocator protein (TSPO) is a mitochondrial protein up-regulated in colorectal carcinoma (CRC). Our purpose was to develop a TSPO-targeted doxorubicin prodrug (Dox-TSPO) which can be loaded onto drug-eluting beads for transarterial chemoembolization. Furthermore, we evaluated its loading and release kinetics and effects on cell viability. Materials and methods N-Fmoc-DOX-14-O-hemiglutarate was coupled with a TSPO ligand, 6-TSPOmbb732, using classical N,N,N',N'-tetramethyl-O-(1H-benzotriazol-1-yl)uranium hexafluorophosphate coupling to produce Dox-TSPO. Loading and elution studies were performed using DC beads™. Cell viability studies were performed using CellTiter-Glo® Luminescent Cell Viability Assay. Results Dox-TSPO was successfully synthesized and readily loaded onto and eluted from DC beads™, albeit at a slower rate than free doxorubicin. CRC cell lines expressing TSPO were 2- to 4- fold more sensitive to Dox-TSPO compared to free doxorubicin at 72 h. Conclusion Dox-TSPO is a promising candidate for targeted and directed cancer treatment of CRC liver metastases.

Background Physician burnout is a common problem that can have negative ramifications for both physicians and patients. Lack of effective coping mechanisms decreases resilience, which can lead to burnout, and women may be particularly vulnerable. Objective We aimed to evaluate resilience by generation among professionals in dermatology. We hope to gain a better understanding of the plasticity of resilience traits to identify modifiable resilience components. Methods Attendees of the 2020 Women’s Dermatological Society Forum were asked to complete an 80-item questionnaire evaluating eight characteristics of resilience. Each participant received scores electronically, and attendees were invited to anonymously submit scores, job category (physician or industry), and birth year and/or generation category. Participants who provided scores and were part of the millennial generation (born 1980–1994; ages 26–40 years at the time of survey completion), Generation X (born 1965–1979; ages 41–55 years), or baby boomer generation (born 1944–1964; ages 56–76 years) were included. Results Of the 67 participants meeting the inclusion criteria, 96.7% were women and 3.3% were men, 69.4% were physicians and 30.6% were industry representatives. Millennials accounted for 43.3%, Generation X for 35.8%, and baby boomers for 20.9% of the study participants. There was a significant difference among the three generations for mean scores on rumination (p = .0071) and flexibility (p = .0005), with scores becoming more ideal for older generations. There was no significant difference among generations for other resilience or burnout indicators, including emotional inhibition, toxic achieving, avoidance coping, perfect control, detached coping, and sensitivity. Conclusion Resilience traits such as rumination and flexibility differed by generation, with the most favorable scores occurring in the oldest cohort, suggesting that some resilience traits may be malleable and improve with age or be inherently affected by environment during development. Health care professionals may benefit from engaging in activities that enhance malleable resilience traits and improve the ability to manage work-related stressors.

Clinical trials are currently underway to evaluate the benefit of dupilumab in treating allergic contact dermatitis (ACD). Dupilumab use has been reported to improve ACD reactions in some patients, but not all. Varying clinical responses to T helper 2 (TH2) inhibition challenge the classical view that ACD proceeds through a TH1-dominant pathway. Selective TH2 inhibitors, such as dupilumab, may attenuate ACD when the delayed hypersensitivity response is due to TH2-predominate activation; conversely, it may have no effect on ACD if it is elicited via TH1 or TH17 pathways. We hypothesize that allergen-specific T-cell responses and patient-specific factors both play an important role in determining which pathways are recalled in delayed hypersensitivity reactions.

To analyze tumor response, survival and safety in patients with non-resectable hepatocellular carcinoma (HCC) treated with transarterial hepatic chemoembolization using degradable starch microspheres (DSM-TACE) combined with doxorubicin who had no local interventional or systemic therapy alternative according to an interdisciplinary conference. In this retrospective study, 28 patients (23 male, 5 female, median age 67 years) with unresectable HCC, serum bilirubin levels 3 mg/dl and contraindications to Sorafenib, RFA, SIRT or cTACE were included. DSM-TACE was performed using Embocept DSM-TACE could be technically successfully performed in all 28 patients. At control imaging after three treatments, the overall rates of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were 14.3 %, 25 %, 39.3 % and 21.4 %, respectively, according to mRECIST. With regard to BCLC stages, the results were as follows (CR, PR, PD): BCLC A (n = 8): 7.1 %, 7.1 %, 10.7 %, 1.2 %; BCLC B (n = 12): 0 %, 10.7 %, 17.9 %, 14.3 %; BCLC C (n = 5): 0 %, 3.6 %, 10.7 %, 3.6 %; BCLC D (n = 3): 3.6 %, 3.6 %, 0 %, 3.6 %. According to this, DSM-TACE showed an overall good median survival of 682 days, although the patients' survival was strictly dependent on BCLC stage. DSM-TACE is a safe and promising treatment alternative for patients with unresectable HCC who are ineligible for other loco-regional therapies. · DSM-TACE is a safe treatment alternative for patients ineligible for other local or systemic treatments.. · DSM-TACE did not influence the MELD-score in our study population.. · Patients treated with DSM-TACE showed an overall good median survival of 682 days, strictly dependent on BCLC stage..· Haubold J, Reinboldt MP, Wetter A et al. DSM-TACE of HCC: Evaluation of Tumor Response in Patients Ineligible for Other Systemic or Loco-Regional Therapies. Fortschr Röntgenstr 2020; 192: 862 - 869. Die Studie wurde durchgeführt, um das Tumoransprechen, das Überleben und die Sicherheit der Behandlung durch transarterielle Chemoembolisation mit abbaubaren Stärke-Mikropartikeln in Kombination mit Doxorubicin (DSM-TACE) bei Patienten mit inoperablem hepatozellulärem Karzinom (HCC) zu analysieren. Die Patienten hatten dabei gemäß einer interdisziplinären Konferenz keine lokale oder systemische Therapiealternative. In diese retrospektive Studie wurden 28 Patienten (23 männlich, 5 weiblich, mittleres Alter 67 Jahre) mit inoperablem HCC, Serum-Bilirubinspiegel 3 mg/dl und Kontraindikationen gegen andere lokale oder systemische Therapien eingeschlossen. DSM-TACE wurde 3-mal alle 4–6 Wochen mit Embocept DSM-TACE konnte bei allen 28 Patienten technisch erfolgreich durchgeführt werden. Bei der Kontrollbildgebung nach 3 Therapien lagen die Gesamtraten für das vollständige Ansprechen (CR), das partielle Ansprechen (PR), die stabile Erkrankung (SD) und die progressive Erkrankung (PD) laut mRECIST bei 14,3 %, 25 %, 39,3 % bzw. 21,4 %. In Bezug auf die BCLC-Stufen ergaben sich folgende Ergebnisse (CR, PR, PD): BCLC A (n = 8): 7,1 %, 7,1 %, 10,7 %, 1,2 %; BCLC B (n = 12): 0 %, 10,7 %, 17,9 %, 14,3 %; BCLC C (n = 5): 0 %, 3,6 %, 10,7 %, 3,6 %; BCLC D (n = 3): 3,6 %, 3,6 %, 0 %, 3,6 %. Dementsprechend zeigte die DSM-TACE ein insgesamt gutes medianes Überleben von 682 Tagen, wobei das Überleben der Patienten streng vom BCLC-Stadium abhängig war. DSM-TACE ist eine sichere und vielversprechende Behandlungsalternative für Patienten mit einem inoperablen HCC, die für andere lokale und systemische Therapien nicht geeignet sind. · DSM-TACE ist eine sichere Behandlungsalternative für Patienten mit einem HCC, die für andere lokale und systemische Therapien nicht geeignet sind.. · DSM-TACE hatte in unserer Studienpopulation keinen Einfluss auf den MELD-Score.. · Die mit DSM-TACE behandelten Patienten zeigten ein insgesamt gutes medianes Überleben von 682 Tagen, das strikt vom BCLC-Stadium abhängig war..

OBJECTIVE During cochlear implantation, electrophysiological tests are performed to document safe technical functioning of implant and electrodes. In rare cases, the apical part of the electrode folds over during insertion. The data from transimpedance matrix (TIM) measurements enable the generation of a heat map or TIM profile measuring the spatial distribution of voltage. The aim of this study was to determine the accuracy of heat-map TIM profiles and compare them with spread of excitation (SOE) measurements and intraoperative imaging for prediction of electrode malposition. STUDY DESIGN Non-randomized study. SETTING Tertiary referral center. PATIENTS AND INTERVENTIONS One hundred patients who underwent cochlear implantation with completed TIM measurements, SOE data and perioperative imaging met the inclusion criteria and were enrolled. MAIN OUTCOME MEASURE The electrophysiological data on the electrode array positioning was compared with temporal bone imaging. RESULTS In seven cases, TIM measurements showed irregular results. In two cases, irregular TIM profiles were registered, but SOE data and 3D x-ray of the temporal bone didn't display deviated electrode positioning. A 3D x-ray of the skull displayed electrode tip fold-over in four cases and electrode buckling in one case. Sensitivity of TIM measurements and SOE data was 100%, specificity of TIM measurements was 97.89%, and specificity of SOE data was 98.93%. CONCLUSION Out of 100 patients using TIM measurements for detection of electrode malpositioning, no false negative cases were detected. TIM measurements successfully detect electrode malposition in an intraoperative setting. Different heat map patterns may be observed depending on location and type of malposition.

To evaluate the safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) for the treatment of hepatocellular carcinoma (HCC) with a high tumor burden ineligible for or failing other palliative therapies, 121 patients from three European centers were included. Kaplan–Meier analysis was used for median overall survival (OS) and time to progression (TTP, mRECIST criteria) in months with a 95% confidence interval (95% CI). Uni- (UVA) and multivariate (MVA) analyses were performed using the Cox Proportional Hazard Model. The median OS of the study cohort was 15.5 (13.3–18.7) months. The UVA identified HCC lesions ≤10 cm, unilobar involvement, lower Child–Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage, absence of vascular invasion, and extrahepatic metastases as factors for prolonged survival. MVA confirmed lesions of ≤10 cm and unilobar disease as independent OS factors. Median TTP was 9.5 (7.6–10.3) months. The best response was achieved after a median of 3 (range: 1–6) treatments with CR/PR/SD/PD in 13.5%/44.5%/25.2%/16.8%, respectively. DSM-TACE was well tolerated with no major clinical adverse events and only limited major laboratory events. Preserved liver function was observed after repetitive DSM-TACE treatments. Repetitive DSM-TACE is a safe, well-tolerated and effective treatment option for HCC patients with high tumor burden ineligible or failing other palliative therapies.

Objective: Evaluation of the efficacy and safety of atezolizumab/bevacizumab in a real-world HCC cohort, including patients with impaired liver function and prior systemic therapy. Methods: Retrospective analysis of 147 HCC patients treated with atezolizumab/bevacizumab at six sites in Germany and Austria. Results: The overall response rate and disease control rate were 20.4% and 51.7%, respectively. Seventy-three patients (49.7%) met at least one major exclusion criterion of the IMbrave150 trial (IMbrave-OUT), whereas 74 patients (50.3%) were eligible (IMbrave-IN). Median overall survival (mOS) as well as median progression-free survival (mPFS) was significantly longer in IMbrave-IN versus IMbrave-OUT patients [mOS: 15.0 months (95% confidence interval (CI): 10.7–19.3] versus 6.0 months (95% CI: 3.2–8.9; p Conclusion: In this real-world cohort, efficacy was comparable to the results of the IMbrave150 study and not affected by prior systemic treatment. ALBI grade and ECOG score were independently associated with survival. IMbrave-OUT patients were more likely to experience hepatic decompensation.

Design thinking is a powerful platform that provides the structure and process to measure integrated experiential learning (IEL). IEL situates the activities of experiential learning in an interdisciplinary setting that facilitates learning through reflection on experiences that engage deep knowledge in broad applications and span co-curricular and curricular environments. Using courses developed at two institutions as case studies, the authors describe pedagogy, instruction, and assessment methods, and focus the data types, collection, analysis, and implications of three assessment approaches (reflections, networks, and deliverables). They show how design thinking is essential to the assessment of IEL in courses and across institutional stakeholders, including student and academic affairs, alumni relations, employers and local businesses, and those focused on data for improvement in design (e.g., institutional research and legislators). Moreover, they show that the assessment phase of design thinking is essential to sustainability, scalability, and rigor of design thinking IEL projects.

Associations between socioeconomic status (SES) and personality traits have important implications for theory and application. Progress in understanding these associations depends on valid measurement, unbiased estimation, and careful assessment of generalizability. In this registered report, we used data from AIID, a large online study, to address three basic questions about personality and SES. First, we evaluated the measurement invariance of a common measure of personality, the Big Five Inventory, across indicators of educational attainment, income, and occupational prestige. Fit indices showed some instances of detectable noninvariance, but with little practical impact on substantive results. Second, we estimated associations between SES and personality. Results showed that personality and SES were largely independent (most rs < .1), in contrast to predictions derived from several previous studies. Third, we tested whether age trends in personality were moderated by SES. Results did not support predictions from social investment theory, but they did suggest that age trends were largely generalizable across SES. We discuss the implications of these findings for developing and validating personality measures for use in diverse samples. We also discuss the implications for theories that propose that the Big Five are responsive to, or partially responsible for, people’s economic and social conditions.

Establishing reliable predictors of health behavior is a goal of health psychology. A relevant insight from personality psychology is that facets can predict specific behaviors better than broad traits do. We hypothesized that we could predict physical activity with a facet of conscientiousness related to goal pursuit—planfulness. We measured the relationship between Planfulness Scale scores and physical activity in 282 individuals over a total of 20 weeks, using a piecewise latent growth curve model. We additionally tested whether planfulness uniquely relates to activity when compared with related constructs. Finally, ratings of participants’ written goals were correlated with these personality traits and physical activity. We found that planfulness was positively associated with average visits to a recreational center, that planfulness explained unique variance in activity, and that planfulness correlated with the descriptiveness of written goals. We conclude that the Planfulness Scale is a valid measurement uniquely suited to predicting goal achievement.

Background To investigate the impact of insurance status on outcomes in patients with hepatocellular carcinoma (HCC). Methods Patients diagnosed with HCC in the cancer registry from 2005 to 2016 were retrospectively stratified by insurance group. Overall survival was assessed via Kaplan‐Meier curves and Cox proportional hazard models including potential confounders in multivariable analyses. Results Seven hundred and sixty‐nine patients met inclusion criteria (median age 63 years, 78.8% male, 65.9% Caucasian). 44.5% had private insurance (n = 342), 29.1% had Medicare (n = 224), and 26.4% had Medicaid (n = 203). At diagnosis, Medicaid patients had higher rates of Child‐Pugh B (32.0%) and C disease (23.6%) vs Medicare (28.6% and 9.8%) and private insurance (26.9% and 6.7%, P, Medicaid is associated with advanced liver cirrhosis at time of hepatocellular carcinoma diagnosis. Primary insurance is not an independent predictor of survival.

Background Challenges today are complex and rapid innovations are required. We instruct a transdisciplinary undergraduate course where engineering, nursing, and pre-professional health students produce tangible innovative solutions to community health challenges using MakerSpace technologies. Students receive evidence-based ethics instruction as part of the course using the 8 Key Questions for improving ethical reasoning. Design thinking, an empathy-based problem solving technique, was used to teach problem solving and provided context for instructing ethical reasoning. Objective The Objective of this research was to assess student ethical reasoning pre/post this course where students concurrently produce innovative products. Design/Participants Undergraduate students were assessed pre/post course for their perceptions of 1) the importance of, and 2) their confidence in their ability to ethically reason using a digital version of the Survey of Ethical Reasoning, an instrument previously tested in this population. Results Participants demonstrated a significant gain in their ethical reasoning confidence and maintained their high ranking of the importance of ethical reasoning concurrently to producing innovative products. Conclusions It is possible, with deliberate instruction, for transdisciplinary undergraduate students to develop ethical reasoning confidence concurrently to developing innovative products.

Die bildgebende Diagnostik und Therapieuberwachung von Erkrankungen thorakaler Organe ist auf unterschiedliche Art und Weise moglich. Zur Verfugung stehen sonographische, magnetresonanztomographische sowie verschiedene radiologische und nuklearmedizinische Verfahren. Eine Uberdiagnostik und die unnotige Verwendung von Rontgenstrahlung sollten aus medizinisch und wirtschaftlichen Grunden vermieden werden. Die erste apparative Methode, um weitere diagnostische und therapeutische Schritte effektiv und zeitnah zu planen, ist neben der klinischen Untersuchung meist die Thoraxsonographie. Diese Arbeit bietet eine aktuelle Ubersicht uber die Moglichkeiten, die die differenzierte Thoraxsonographie in der elektiven Diagnostik, in der Notfalldiagnostik sowie als interventionelles Verfahren bietet. Neben Indikationen und Grenzen der Thoraxsonographie werden Vorteil fur diagnostische und therapeutische Interventionen im Vergleich zur Computertomographie aufgezeigt und aufkommende zusatzliche technische Moglichkeiten dargestellt.

Image-guided locoregional therapies (LRTs) have long been a vital part of treatment regimens for hepatocellular carcinoma (HCC). Ablation, chemoembolization, and radioembolization are examples of commonly used treatment techniques for HCC. This review describes the various methods utilized to treat HCC in the field of interventional oncology and also focuses on new and novel treatment concepts being developed in the field including the use of novel immunotherapy agents and combination therapy of LRTs with immunotherapy.

The aim of the current study was to compare the diagnostic precision and reliability of different methods in measuring Hill–Sachs lesions (HSLs) using MRI and CT. A total of 80 consecutive patients with a history of anterior shoulder instability were retrospectively included. The preoperative CT and MRI scans of the affected shoulders were analysed. To investigate the ability of the Franceschi grading, Calandra classification, Richards, Hall, and Rowe grading scale, Flatow percentage and “glenoid track” assessment according to Di Giacomo et al. to quantify the extent of humeral bone loss, the results of each measurement method obtained with MRI were compared with those achieved with CT. In addition, the intra- and inter-rater reliabilities of each measurement method using CT and MRI were calculated and compared. A significant difference was found between CT and MRI in the determination of the Hill–Sachs interval (HSI) (p = 0.016), but not between the results of any of the other measurement techniques. With the exceptions of the Franceschi grade and Calandra classification, all measurement methods showed good or excellent intra- and inter-rater reliabilities for both MRI and CT. While the determination of the HSI with MRI was more accurate, all other analysed techniques for measuring the amount of humeral bone loss showed similar diagnostic precision. With regard to the intra- and inter-rater reliabilities, all measurement techniques analysed, with the exception of the Franceschi and Calandra classifications, provided good to very good reliabilities with both CT and MRI. III

Checkpoint inhibitors have demonstrated clinical impact in colorectal cancer with deficient mismatch repair and high microsatellite instability. However, the majority of patients have disease with stable microsatellites that responds poorly to immunotherapies. Combinations of checkpoint inhibitors are under investigation as a way of increasing immunogenicity and promoting a robust anti-tumor immune response. The purpose of this study is to quantify the immune responses induced by mono and dual checkpoint inhibition in a mismatch repair proficient model of colorectal cancer (CRC). Tumor growth rates were monitored over time and compared between groups. We utilized fluorescence-activated cell sorting to analyze CD8+ and CD4+ T cells after treatment with either single PD-1 inhibition or dual PD-1 and CTLA-4 inhibition. Additionally, we sought to quantify the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3. Dual checkpoint inhibition was associated with a significantly slower growth rate as compared to either mono PD-1 inhibition or control (p + T cells demonstrated significantly less expression of PD-1 (1700 vs. 2545 and 2462; p p p

LOPES, the LOFAR prototype station, was an antenna array for cosmic-ray air showers operating from 2003 - 2013 within the KASCADE-Grande experiment. Meanwhile, the analysis is finished and the data of air-shower events measured by LOPES are available with open access in the KASCADE Cosmic Ray Data Center (KCDC). This article intends to provide a summary of the achievements, results, and lessons learned from LOPES. By digital, interferometric beamforming the detection of air showers became possible in the radio-loud environment of the Karlsruhe Institute of Technology (KIT). As a prototype experiment, LOPES tested several antenna types, array configurations and calibration techniques, and pioneered analysis methods for the reconstruction of the most important shower parameters, i.e., the arrival direction, the energy, and mass-dependent observables such as the position of the shower maximum. In addition to a review and update of previously published results, we also present new results based on end-to-end simulations including all known instrumental properties. For this, we applied the detector response to radio signals simulated with the CoREAS extension of CORSIKA, and analyzed them in the same way as measured data. Thus, we were able to study the detector performance more accurately than before, including some previously inaccessible features such as the impact of noise on the interferometric cross-correlation beam. These results led to several improvements, which are documented in this paper and can provide useful input for the design of future cosmic-ray experiments based on the digital radio-detection technique., Comment: Accepted for publication by EPJ C

The amount of neuroimaging data being shared increased exponentially in recent years. While thisdevelopment introduces prominent advantages concerning open, reproducible and sustainable neu-roimaging, the process of data sharing must ensure the privacy of participant data. A requirement fromboth, Ethics Review Boards and data sharing resources, datasets need to be (pseudo-) anonymized priorto sharing in order to limit participant re-identification. Depending on the dataset at hand, this processcan however become cumbersome and prone to errors. Here we introduce BIDSonym, a tool for auto-mated pseudo-anonymization of neuroimaging datasets. BIDSonym supports multiple de-identificationprocedures and operates on neuroimaging, as well as metadata files. In addition, all metadata infor-mation present in the respective files is gathered and evaluated. Its outputs furthermore allow usersto conduct a more in-depth assessment of potentially sensitive information present in a given dataset.Through its workflow and utilization of the Brain Imaging Data Structure (BIDS), BIDSonym’s appli-cation is reproducible, requires no manual intervention and is agnostic to idiosyncrasies of small andlarge scale datasets.

Purpose Numerous endeavors have been undertaken to preserve hearing in cochlear implant (CI) patients. Particularly, optimization of electrode array design aims at preservation of residual hearing (RH). This study examines whether a slim perimodiolar (PM) electrode array could bear the capability to preserve hearing. Methods A total of 47 patients underwent cochlear implantation receiving the PM electrode. (i) Patients with pure tone audiogram (PTA) thresholds better than 85 dB and/or hearing loss for Freiburg speech test numbers less than 60 dB and more than 50% maximum monosyllabic understanding were assigned to the RH group (n = 17), while all others belonged to the noRH group (n = 30). (ii) Another group implanted with a slim straight, lateral wall (LW) electrode was recruited for comparison. Results We compared 17 RH–30 noRH patients all receiving the PM electrode. RH in PM recipients decreased faster than in LW recipients. No significant differences were observed between both (RH v/s noRH) groups in NRT thresholds, Freiburg speech test and A§E® phonemes. Analogous satisfaction levels were indicated through the questionnaires in terms of sound quality, hearing in silence, noise and directional hearing in both groups. Conclusions The results suggest that hearing preservation is influenced not only by electrode shape but various factors. This study opens an avenue for further investigations to elucidate and enumerate the causes for progressive hearing loss.

Simple Summary In this European multicenter study, we investigated the treatment efficacy and safety of degradable starch microsphere transarterial chemoembolization (DSM-TACE) for HCC treatment in 121 patients in whom other standard therapies failed or patients were not eligible. Patients survived a median of 15.5 months with a median time to tumor progression of 9.5 months and a disease control rate of 83.2%. The patients who survived longer had HCC lesions ≤10 cm, the involvement of one liver lobe only, lower Child–Pugh class and Barcelona Clinic Liver Cancer (BCLC) tumor stage, absence of vascular invasion, and the absence of extrahepatic metastases. Of these factors, a lesion of ≤10 cm and unilobar disease were identified as independent survival factors. Safety analysis revealed low rates of adverse events and maintained liver function after several treatments regardless of the treated liver volume. Thus, DSM-TACE is a veritable treatment alternative for unresectable HCC, where other treatments fail or cannot be offered due to contraindications. Abstract To evaluate the safety and efficacy of transarterial chemoembolization with degradable starch microspheres (DSM-TACE) for the treatment of hepatocellular carcinoma (HCC) with a high tumor burden ineligible for or failing other palliative therapies, 121 patients from three European centers were included. Kaplan–Meier analysis was used for median overall survival (OS) and time to progression (TTP, mRECIST criteria) in months with a 95% confidence interval (95% CI). Uni- (UVA) and multivariate (MVA) analyses were performed using the Cox Proportional Hazard Model. The median OS of the study cohort was 15.5 (13.3–18.7) months. The UVA identified HCC lesions ≤10 cm, unilobar involvement, lower Child–Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage, absence of vascular invasion, and extrahepatic metastases as factors for prolonged survival. MVA confirmed lesions of ≤10 cm and unilobar disease as independent OS factors. Median TTP was 9.5 (7.6–10.3) months. The best response was achieved after a median of 3 (range: 1–6) treatments with CR/PR/SD/PD in 13.5%/44.5%/25.2%/16.8%, respectively. DSM-TACE was well tolerated with no major clinical adverse events and only limited major laboratory events. Preserved liver function was observed after repetitive DSM-TACE treatments. Repetitive DSM-TACE is a safe, well-tolerated and effective treatment option for HCC patients with high tumor burden ineligible or failing other palliative therapies.