Search

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Pfizer Global Medical Grant Background Amyloid transthyretin cardiomyopathy (ATTR-CM) is a progressive infiltrative cardiomyopathy caused by extracellular deposition of amyloid fibrils. The disease is characterized by congestive heart failure, conduction abnormalities and arrhythmias. Due to the limited overall prognosis, ICDs were rarely indicated in ATTR-CM. However, with the development of new targeted therapies, the role of ICD therapy for ATTR-CM should be reevaluated. Hence, there is an urgent and unmet need to identify patients at high risk for ventricular tachycardias who might possibly benefit from ICD therapy. Methods Between 2020 and 2022, 120 patients were diagnosed with ATTR-CM in a tertiary referral center. Of those, 63 were prospectively evaluated for the presence of ventricular arrhythmias using 24 hours Holter-ECG. Ventricular arrhythmias were further characterized as sustained (sVT) and non-sustained ventricular tachycardias (nsVT). Results In our cohort of unselected ATTR-CMP patients the prevalence of ventricular tachycardias was high with 47.6 % (n= 30/63). Of those, the majority were non-sustained VTs (84%) and the minority sustained VT (16%). Patients with ventricular tachycardias showed significantly more severe left ventricular (LV) hypertrophy, reduced LV ejection fraction (LV-EF) and larger left atrial volumes as well as a trend towards smaller LV cavities (table 1). Interestingly, no significant differences in prevalence of coronary artery disease or cardiac markers such as NTproBNP and troponin were seen between patients with and without ventricular tachycardias (table 1). Furthermore, we evaluated the multivariable predictive performance for discriminating between patients with and without ventricular tachycardias using two backward variable selection procedures (model 1 p-value based and model 2 Akaike information criterion (AIC) based). In the first model, LVEF (OR = 0.865 [0.776;0.963], p=0.008), LVEED (0.837 [0.708;0.991], p=0.039), and LV mass indexed by BSA (1.028[1.003;1.055], p=0.031) remained independent predictors of occurrence of ventricular arrhythmias, while in the second model sodium concentration (1.287 [0.929;1.783], p=0.129) and betablocker medication (5.078, [0.819;31.477], p=0.081) also were retained. Comparing the area under the Receiver Operating-Characteristic (AUROC) we observed no significant difference between both models (AUROC: 0.846 [0.711;0.937] vs. 0.870 [0.737;0.951], p=0.57, figure 1). Conclusion The prevalence of ventricular tachycardia in ATTR-CM is high. Patients with ventricular tachycardia show advanced stage of left ventricular disease, with LVEDD, LV-EF and LV mass indexed by BSA being predictors of ventricular tachycardias in two multivariable predictive models. Further studies validating the predictive value of those variables are needed, including the assessment of nsVT and sVT in predicting sudden cardiac death, possibly allowing the use as a risk score for ventricular arrhythmias.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Deutsche Stiftung für Herzforschung research grant Background Electromagnetic interference (EMI) poses a risk to patients with cardiac implantable devices (CIEDs) and can result in device malfunction including pacing inhibition or inappropriate shock therapy. Such EMI sources are ubiquitous in the modern world. Battery electric vehicles (BEVs) represent such a potential EMI source. We have previously investigated the EMI risk of driving eCars and found that the largest electromagnetic field is located along the charging cable. New high power chargers deliver higher currents (facilitating rapid recharging), potentially associated with greater electromagnetic fields and higher risk for clinically relevant EMI. This present study aims to evaluate this EMI-risk to address this clinically important question. Methods A consecutive group of 130 patients with a range of CIEDs were recruited to participate. After a complete device interrogation each had their device programmed to optimise EMI detection with ensured ventricular pacing and ICD therapies were disabled. Under continuous 6-lead ECG monitoring each patient then plugged in and charged four different BEVs (Porsche Taycan Turbo, VW ID3 pro, Tesla Model 3 and Audi e-tron 55 Quattro) in addition to a ‘dummy’ eCar (which permitted the maximal charging power flow of 350kW) with the charging cable placed directly over the device. During charging both the magnetic field and electric field was measured. A further complete device interrogation was then performed to evaluate for spontaneous reprogramming and tachycardia detection. Results In total 561 separate charging events were performed by 130 patients with the four eCars and one dummy car. The maximal magnetic field along the charging cable was 38.65µT and at the charging column was 77.9µT. There were no incidences of EMI, specifically there was no pacing inhibition due to oversensing, no spontaneous reprogramming and no tachycardia over-detection. This results in a patient-based risk of 0% (95% CI; 0% - 2.8%) and a charging event-based risk of 0% (95% CI; 0% - 0.6%). Conclusions and Discussion We found that there was no EMI induced during the use of high power charger technology for BEV despite device programming and charging cable placement being optimised for a worst-case scenario and maximising the chance of clinical EMI. Our study suggests that there is a very low risk, if any, posed by BEVs and the new high power chargers. CIED patients should reassured that their use is safe. We would still recommend not to place the charging cable directly above the CIED during use to maximise safety of high power charging.

Funding Acknowledgements Type of funding sources: None. Aims Pulse field ablation (PFA) is a novel catheter ablation technology with safety benefits due to its tissue selectivity. The risk of physical damage or electromagnetic interference (EMI) of PFA with cardiac implantable electronic devices (CIEDs) is unknown. The aim of our study was to assess the risk of PFA for CIEDs. Methods PFA lesions (45 per CIED) were applied to CIEDs ( Results In total, 44 CIEDs were tested (16 pacemaker, 21 ICDs, 7 CRT-P/D) with 1,980 PFA applications. There was no change in device settings, functionality, electrical parameters and there was no visible damage to the CIEDs or leads. The risk on a device-based analysis is 0/44 (95% CI 0%-8%) and on a PFA pulse-based analysis is 0/1,980 (95% CI 0%-0.2%). Clinically relevant EMI appeared with oversensing and pacing inhibition, but not tachycardia detection. Conclusions Bipolar PFA appears safe and does not result in damage to CIEDs or leads. Clinically relevant EMI does occur, but appropriate peri-procedural programming may mitigate this. In-vivo studies are needed to confirm our findings.

Aims To investigate the effectiveness of a combined telemonitoring and telecoaching programme for chronic heart failure patients at high risk for hospitalisation compared to usual care in a real life setting. The applied telehealth programme consisted of regular individualised telecoaching sessions as well as daily remote telemonitoring of heart failure signs and symptoms. Methods Between January 2018 and September 2020, 6,065 heart failure patients were enrolled in a combined telehealth programme and retrospectively compared to a propensity matched usual care group (n=6,065). All participants were members of a statutory health insurance. Median follow-up was 442 days (IQR 309–681). Endpoints were all cause mortality, number and duration of hospitalisations. Results After 1 year the combined telecoaching and telemonitoring programme significantly reduced all-cause mortality probability compared to usual care (11.0 vs. 5.8%, p0.001, respectivel y) were significantly lower in the telehealth group than in the usual care group. Conclusion In ambulatory heart failure patients at high risk for hospitalisation, a combined telemonitoring and telecoaching programme led to a reduction of heart failure hospitalisations and all-cause mortality compared to standard care. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Health Care Systems GmbH (HCSG), Pullach i. Isartal

Purpose The aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer diagnoses throughout the year 2020 in a gynecological oncological center in Austria. Methods Data of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 to April 2020 and the second lockdown from November 2020 to December 2020 and compared to the same period in 2019. Results Our results showed a strong decline in newly diagnosed cancers during the lockdown periods: −45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% vs. 31%, p = 0.013) during and in between (48% vs. 32%, p = 0.022) the lockdowns. During the lockdown, periods in the group of breast cancer patients’ tumor stage varied significantly compared to 2019 (T2–T4; p = 0.047). Conclusion Both lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.

Funding Acknowledgements Type of funding sources: None. Introduction The implantation of cardiac implantable electronic devices (CIEDs) such as pacemakers and implantable cardioverter-defibrillators is increasing along with the complexitly of these devices. CIED infection is an uncommon, but severe complication associated with the presence of a device and is associated with a high mortality and morbidity. Lead-related infections and frank endocarditis are associated with a systemic inflammatory response and, in general, are readily identified. Isolated pocket infections do not produce such a systemic response and are thus more complex to diagnose. There is a reliance on clinical accumen and examination of local signs of infection. There is thus a need for a reliable biomaker to help identify cases of pocket infection. Aim Our group have previously shown procalcitonin (PCT) to be a potentially useful biomaker in the clinial situation of possible pocket infection. We aim to prospectively validate the proposed cut-off value of 0.05ng/ml for the procalcitonin (PCT) biomaker in an independent cohort, which we have previously identified as showing promise in this clinical situation. Methods In this prospective case-control validation study the PCT levels of 81 patients with confirmed pocket infections were compared to 81 controls, matched for age and renal function, presenting for elective generator replacement or lead revision unrelated to infection. Exclusion criteria included: concomitant infectious or inflammatory diseases, end-stage renal failure, active malignancy or receiving immunosuppressive therapy. Results A PCT over 0.05 ng/ml was found in 68% (n= 55) of pocket infections and 24% (n= 19) of controls. Using the pre­defined cut-off value of 0.05 ng/ml PCT had a sensitivity of 68% and a specificity of 77% for diagnosing pocket infections. ROC analysis revealed area under the curve of 0.752 (standard error 0.039, p Conclusion PCT is a potentially useful biomarker to aid the diagnosis of a pocket infection when used with the prospecitvely validated cut-off value of 0.05ng/ml. The sensitivity of the PCT positive result remained high even in patients pre-treated with antibiotics or with minimal clinical signs of inflammation.

Funding Acknowledgements Type of funding sources: None. Introduction The rate of transvenous lead extraction (TLE) is increasing with an increasing rate of complex devices being implanted. TLE is now a routine part of cardiac device management and up to date data on the safety and efficacy of TLE with modern tools and techniques is essential to management decisions regarding non-infectious indications for lead extraction. Purpose To evaluate the safety and efficacy of TLE in a contemporary cohort using mechanical (non-laser) extraction tools. Methods We present a contemporary, prospective review of TLE at our high-volume cardiac centre. All patients undergoing TLE from June 2016 and June 2019 were enrolled in our local database and baseline clinical data, procedural information and outcome data were collected. Results In total 561 leads were explanted (n=153) or extracted (n=408) from 341 patients over the study period. Patients were predominantly male (71%) with a mean age of 65 ± 17 years. The most common indication for lead removal was lead failure (45.2%, n=154) followed by infection of the pocket or device (29.3%, n=100). The mean dwell time of the 408 extracted leads was 7.2 years; 35% had a dwell time of 5-10 years, 23% had a dwell time >10 years and 4% had a dwell time >20 years (Figure 1). In total, complete success was achieved in 96.4% (n=541) leads, clinical success in a further 2.1% (n=12) and failure only in 1.4% (n=8). Clinical success was high (93%) even in leads with dwell time >20 years (Figure 2). There was an overall complication rate of 0.9% (3/341) for major complications and 1.5% (5/341) for minor complications. There were no deaths. Conclusions Our data would suggest that there are ongoing improvements in the safety profile and success rates of lead extraction undertaken by experienced operators now with a major complication rate of

BackgroundOn March 16, 2020, the federal government of Austria declared a nationwide lockdown due to the COVID-19 pandemic. Since the lockdown, screening examinations and routine checkups have been restricted to prevent the spread of the virus and to increase the hospitals’ bed capacity across the country. This resulted in a severe decline of patient referrals to the hospitals.ObjectiveTo assess the impact of the COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers in Austria.MethodsData of 2077 patients from 18 centers in Austria with newly diagnosed gynecological or breast cancer between January and May 2019 and January and May 2020 were collected. Clinical parameters, including symptoms, performance status, co-morbidities, and referral status, were compared between the time before and after the COVID-19 outbreak.ResultsOur results showed a slight increase of newly diagnosed cancers in January and February 2020 as compared with 2019 (+2 and +35%, respectively) and a strong decline in newly diagnosed tumors since the lockdown: −24% in March 2020 versus March 2019, −49% in April 2020 versus April 2019, −49% in May 2020 versus May 2019. Two-thirds of patients diagnosed during the pandemic presented with tumor-specific symptoms compared with less than 50% before the pandemic (pConclusionsThe lockdown led to a decreased number of newly diagnosed gynecological and breast cancers. The decreased accessibility of the medical services and postponed diagnosis of potentially curable cancers during the COVID-19 pandemic may be a step backwards in our healthcare system and might impair cancer treatment outcomes. Therefore, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future.

SummaryThe recent exciting findings on the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) maintenance therapy in the first-line and later lines of treatment in ovarian cancer are illustrated. Unprecedented advantages have been shown in first-line therapy not only in BRCA-mutated cancers, but also in tumor exhibiting a homologous recombination repair deficiency (HRD) unrelated to BRCA aberrations. The advantages of PARP maintenance therapy in around 50% of HR-proficient high-grade ovarian cancers are far less clear and, even though of statistical significance, the clinical benefit for the patients may be of borderline significance. The pre-treatment testing of HRD remains a matter of debate especially in the light of the current era of precision medicine. Data on the combination of PARPi with bevacizumab maintenance therapy uncovered additive beneficial therapeutic effects. In recurrent ovarian cancer, results on PARPi maintenance therapy after response to platinum-based reinduction chemotherapy are also excellent. At present, however, PARPi maintenance therapy remains reserved for PARPi-naive patients, since the data on PARPi after PARPi is extremely sparse.

Introduction/Background* Endometrial carcinoma patient care was based on histopathologic examination for many years. However, conventional pathologic features are known to suffer from high inter-observer variability and may be irreproducible in many cases. TCGA-derived molecular classification was shown to provide clinically meaningful data and was recently introduced to ESGO/ESTRO/ESP endometrial carcinoma consensus guidelines. It was the aim of this study to quantify alterations in risk-assessment if molecular classification is added to conventional prognosticators. Methodology Consecutive primary endometrial carcinoma patients diagnosed in 2016 were identified in participating centres. Original risk classification (‘ORC16’, ESGO/ESMO guidelines 2016) was compared to current molecular-based risk assessment (‘MBR21’, ESGO/ESMO guidelines 2021). Clinical and histopathological data were collected and tumor specimens were retrospectively submitted to PMS2, MSH6 and p53 immunohistochemistry and POLE mutation testing. Result(s)* 226 patients were identified across five major European gynecologic oncology centres. Complete molecular and clinical data were available from 198 cases with a median follow-up time of 52.1 months. Median age was 64.9 years (30.9-90.9), 165 cases (83,3%) were endometrioid histotype. Grade distribution included 85(42.9%) G1, 63(31.8%) G2, and 46(23.3%) G3 tumors. 98(49.5%) patients had stage IA disease, with the remaining stage IB (n=51;25.8%), stage II (n=16;8.0%), and stage III/IV (n=33;16.7%). Molecular classification yielded 43(21.7%) MMR-D, 18(9.1%) POLE, 43(21.7%) p53abn, and 94(47.5%) p53wt tumors. If ORC16 was compared to MBR21, risk was found to be higher in 15(7.6%) cases, whereas 27(13.6%) cases were assigned to a lower risk group. No survival events were observed in the 9 patients where risk was changed from high-intermediate or high to low-risk. Conclusion* We were able to demonstrate clinically relevant alterations of endometrial carcinoma risk assessment in a significant number of patients after adding TCGA-derived molecular data to conventional risk classification. Potential molecular-guided changes in patient management may help to avoid over- and undertreatment and will ultimately give rise to precision medicine strategies in endometrial carcinoma patient care.

Introduction/Background* The aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer detection rate throughout the year 2020 in a gynecological oncological center in Austria. Methodology Data of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 – April 2020 and the second lockdown from November 2020 – December 2020 and compared to the same period in 2019. Result(s)* Our results showed a strong decline in newly diagnosed cancers during the lockdown periods: -45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% versus 31%, p=0.013) during and in between (48% versus 32%, p=0.022) the lockdowns. During the lockdown periods breast cancer patients were diagnosed with a significantly higher tumor-stage (T2-T4; p=0.047). Conclusion* Both lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.

With the advent of commercially available digital cameras in the late 1990s resulting in the near-exclusion of analog photographic prints today, most archaeological repositories around the world have a mix of analog and digital photographic prints. That ratio is increasingly moving toward digital print processes, of which there are several types. To minimize the loss of image quality, collection managers must become familiar with the unique curation challenges of photographic prints from digitally created images. Likewise, creators of digital content must be aware that choices made when selecting a print process for reposit will have a direct effect on image and print permanence. Site photographs are critical evidence of archaeological activity, and so the preservation of digital prints is in the interest, and is the responsibility, of collection managers and archaeologists alike.

SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2 expression was assessed by RT-PCR in 238 epithelial ovarian cancers (OCs) and put in relation to clinico-pathological parameters and patients’ outcome. Optimal thresholds for high and low expression of both variables were calculated by the Youden’s index based on receiver operating characteristic (ROC) curves. High SMARCA4 mRNA expression was independently associated with favorable progression-free survival (PFS) (P = 0.03) and overall survival (OS) (P = 0.018). As Youden’s threshold determination for EZH2 yielded a S-shaped ROC-curve, two cut-off points (29th and 94th percentile) predicting opposite features were defined. Whereas EZH2 mRNA levels beyond the 29th percentile independently predicted poor PFS (P = 0.034), Cox-regression in EZH2 transcripts above the 94th percentile revealed a conversion from unfavorable to favorable PFS and OS (P = 0.009 and P = 0.032, respectively). High SMARCA4 expression associates with improved survival, whereas moderate/high EZH2 expression predicts poor outcome, which converts to favorable survival in ultra-high expressing OCs. This small OC subgroup could be characterized by REV7-abrogated platinum hypersensitivity but concomitant PARP-inhibitor resistance.

Endometrial cancer (EC) is the most common gynaecologic tumour in the Western world. Previous studies have implicated an imbalance of oestrogens and progestogens in the development of most ECs, while the role of low-grade tissue inflammation remains largely unexplored. We investigated the impact of tumour necrosis factor alpha (TNFα), a central mediator of inflammation and spermatogenesis-associated protein 2 (SPATA2), a regulator of TNF receptor signalling, on clinical outcomes in EC. We evaluated TNFA and SPATA2 transcript levels in 239 EC patients and 25 non-malignant control tissues. Findings were validated in a cohort of 332 EC patients from The Cancer Genome Atlas (TCGA). Expression of TNFA and SPATA2 was increased in EC when compared with control tissues (P < 0.001). TNFA expression correlated with SPATA2 expression in non-malignant (P = 0.003, rS = 0.568) and EC tissue (P = 0.005, rS = 0.179). High TNFA and SPATA2 expression were associated with poor recurrence-free survival (RFS; P = 0.049 and P = 0.018) and disease-specific (P = 0.034 and P = 0.002) survival. Increased SPATA2 expression was also associated with decreased overall survival (OS; P = 0.013). In multivariate analysis, both TNFA and SPATA2 were predictors of clinical outcome. The impact of SPATA2 on RFS and OS could be validated in the TCGA cohort. Our study demonstrates that ECs exhibit a TNF signature which predicts clinical outcome. These findings indicate that TNF signalling modulates the course of EC, which could be therapeutically utilized in the future.

Introduction/Background Mutations in cancer susceptibility genes BRCA1/2 are considered to be associated with better survival in ovarian cancer (OC) patients possibly due to a better response to platinum based chemotherapy and PARP inhibitors. However, the impact of the BRCA1/2 mRNA-expression is not well characterized in OC, but could also influence the platinum response and thus predict the clinical outcome in OC patients. Our previous studies have shown that low BRCA1-expression was associated with favorable overall survival (OS) and low BRCA2-expression with better progression-free survival (PFS) and OS in 201 OC patients. The aim of the present study was to validate the prognostic impact of BRCA expression in OC using the TCGA (The Cancer Genome Atlas) cohort. Methodology Clinical and genomic data were obtained from the OC Dataset of The Cancer Genome Atlas (n=581). Overall and progression free survival was estimated using Kaplan-Meier plots and Cox-Regression. Optimal cut off points were defined using Youden index. Results Univariate survival analysis showed that low BRCA2 expression was associated with favorable PFS (p=0.029) and OS (p=0.011). Multivariable survival analysis confirmed the prognostic value of BRCA2 expression both for PFS and OS. Conclusion Low expression of BRCA2 predicts better survival in patients with OC. Our findings may reflect higher platinum-sensitivity due to reduced capacity of DNA damage repair in tissues with low BRCA2 expression. In this context, especially in BRCA-wildtype cancers BRCA2 expression could also be potential predictor for PARP sensitivity. Disclosure Nothing to disclose.

Introduction/Background The SWI/SNF complex - a chromatin remodelling complex - is recurrently mutated and inactivated in ∼20% of human cancers. Mutations of the SMARCA4 gene, which encodes the ATPase of the SWI/SNF complex, can be found in the majority of small cell carcinomas of the ovary, hypercalcaemic type (SCCOHT). EZH2 is the catalytic subunit of the PCR2 complex, which is an opponent of the SWI/SNF complex. EZH2 inhibitors could play a potential role in the therapy of SCCOHT. The aim of this study was to explore the role of SMARCA4 mRNA-expression in ovarian cancer. Methodology SMARCA4 mRNA-expression was investigated in 20 non-neoplastic fallopian tubes and 276 ovarian carcinomas (OC) (including 144 high grade serous ovarian carcinomas, HGSOC) in relation to their clinical characteristics, p53- and BRCA1/2- mutational status, BRCA1/2 mRNA-expression and EZH2 mRNA-expression. Results The SMARCA4 mRNA-expression in OCs was significantly higher compared to the control group (P A subgroup-analysis of HGSOC showed higher SMARCA4-expression in patients younger than 65 years (P=0,021), in patients without residual disease after surgical debulking (P=0,008) and in patients with early FIGO stages I-II (P=0,004). High SMARCA4-expression was associated with better progression-free survival (PFS) (P=0,05) and better overall survival (OS) (P=0,002). Patients with p53-mutations showed higher SMARCA4-expression (P=0,004). There was a significant correlation between the expression of SMARCA4 and EZH2 (P=0,000 r=0,377). Multivariate Cox-regression model revealed independency of the prognostic value of SMARCA4-expression for OS in patients under the age of 65 years (P=0,015). Conclusion High SMARCA4-expression in patients with HGSOC is associated with younger age at onset of disease, early FIGO stage and with absence of residual disease after primary debulking. In patients younger than 65 years, high SMARCA4-expression is independently associated with better overall survival. Disclosure Nothing to disclose.

The carbon and oxygen isotope compositions of calcium carbonate shells are widely accepted and applied proxies for tracking changes in paleoenvironmental conditions such as temperature, salinity and productivity. In order to accurately interpret isotopic measurements, diagenetic alteration must first be assessed. The occurrence of aragonitic shells is often taken as a first order sign of unaltered material because aragonite at the Earth9s surface is metastable and converts to calcite. However, even specimens that retain an aragonitic composition and are macroscopically well preserved often exhibit subtle to considerable signs of alteration when shell microstructure is examined using scanning electron microscopy (SEM). To determine the textural and isotopic effects of progressive alteration on differing types of shell microstructure, we undertook a comparative study of aragonitic shells from two regions frequently used in paleoenvironmental reconstructions and diagenetic studies – the Upper Cretaceous of the Gulf Coastal Plain (GCP) and the Western Interior Seaway (WIS). Because the GCP is within a passive margin setting and the WIS has experienced tectonic processes, we also evaluate how diagenetic history affects isotopic composition. Visually well-preserved ammonite, bivalve, and gastropod shells were collected from one locality in the GCP and examined using SEM. To evaluate microstructural preservation, we used a previously published scale based on WIS specimens for nacreous shell material and a complementary scale we developed for crossed lamellar microstructure. The stable carbon and oxygen isotope compositions of specimens across the preservational scale from both regions were analyzed. Isotopic composition does not change systematically with degrading preservation in the GCP specimens, a result that contrasts strongly with patterns in WIS specimens where isotopic composition systematically decreases with decreasing microstructural preservation. Dissimilar tectonic regimes that led to unique post-depositional conditions for each region are invoked to explain this difference. The WIS was a foreland basin subjected to significant meteoritic groundwater flow driven by active uplift, while the GCP was a passive margin that has remained close to sea level, with low hydraulic potential, since the time of deposition. Thus, during diagenesis the WIS shells were exposed to fluids that differed greatly from the seawater in which the organisms grew, whereas diagenetic fluids in GCP settings likely were similar to marine waters. As expected, shells with the best-preserved microstructure provide the most consistently reliable isotopic data for paleoenvironmental reconstructions, but our comparisons show that similar degrees of microstructural alteration can express very different diagenetic shifts in isotopic values.

A nationwide lockdown was declared on March 16 in Austria due to coronavirus disease 2019 (COVID-19) outbreak, requiring citizens to remain in their homes except for necessary reasons. The lockdown resulted not only in social distancing and reduction of commercial activity, but also in severe restrictions in the health care system. Regular medical services and outpatient care were nearly shut down to prevent the spread of the virus and to increase the total hospital capacities. Thus, patients faced barriers to attend preventive checkups, such as mammography, screening for cervical cancer, or to consult the general practitioner. As a gynecologic department with a large oncologic subunit, we noticed significantly fewer tumor diagnoses presenting at our department since the lockdown. This phenomenon forced us to perform this retrospective study on newly diagnosed gynecologic and breast cancers before and during the COVID-19 pandemic. A retrospective analysis of newly diagnosed gynecologic and breast cancers presented at the University Hospital Innsbruck from January to May 2019 and from January to May 2020 was performed. Descriptive statistics and analysis of the clinical data stratified by the year of diagnosis were performed using SPSS software and Mann-Whitney U test. Our results showed a slight increase of newly diagnosed cancers in January and February 2020 as compared to 2019 (+13%) and a strong decline in newly diagnosed tumors since the lockdown: -45% in March 2020 vs. March 2019, -63% in April 2020 vs. April 2019, and -44% in May 2020 vs. May 2019. Around two third of patients diagnosed during the pandemic consulted the specialist due to tumor symptoms, while before the pandemic less than 50% of patients presented with symptoms. The ratio of breast and vulvar cancer was significantly higher during the pandemic (71 vs. 61% and 3 vs. 1.9%, respectively; p=0.043), but significantly fewer cervical cancers were diagnosed (4.4 vs. 8.9%; p=0.043). Patients with other malignant, rheumatic, or metabolic disease were rarely diagnosed with a new cancer in 2020 as compared to 2019 (7.5 vs. 12%; 0.7 vs. 3.7% and 6.7 vs. 12%, respectively; p=0.014). A better performance status was observed in patients presented in 2020 as compared to 2019 (p=0.011). In a country with maximum intensive care bed occupancy of 26% during the COVID-19 pandemic, the accessibility of the health care services was severely impaired and preventive care and early cancer detection was restricted, leading to an increase in undetected or postponed tumor diagnoses. The aim of our work is to raise awareness of this issue. It is not clear whether these undetected cases will lead to potential months of life lost; however, decreased accessibility of the medical services and postponed diagnosis of potentially curable cancers are clearly a step backwards in our health care system and will probably impair cancer treatment outcomes. Thus, new strategies to manage early cancer detection are needed to optimize cancer care in a time of pandemic in the future. Citation Format: Irina Tsibulak, Elisabeth Reiser, Christoph Ebner, Katharina Knoll, Katharina Leitner, Verena Wieser, Justina Angerer, Christian Marth. Strong decline of newly diagnosed gynecologic and breast cancers during the COVID-19 pandemic: A retrospective analysis from Innsbruck, Austria [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-038.

The intracellular environment is a dynamic space filled with various organelles moving in all directions. Included in this diverse group of organelles are vesicles, which are involved in transport of molecular cargo throughout the cell. Vesicles move in either a directed or non-directed fashion, often depending on interactions with cytoskeletal proteins such as microtubules, actin filaments, and molecular motors. How these proteins affect the local fluctuations of vesicles in the cytoplasm is not clear since they have the potential to both facilitate and impede movement. Here we show that vesicle mobility is significantly affected by myosin-II, even though it is not a cargo transport motor. We find that myosin-II activity increases the effective diffusivity of vesicles and its inhibition facilitates longer states of non-directed motion. Our study suggests that altering myosin-II activity in the cytoplasm of cells can modulate the mobility of vesicles, providing a possible mechanism for cells to dynamically tune the cytoplasmic environment in space and time., Comment: 10 pages, 5 figures, 3 tables

Objective: To assess and refine competencies for the clinical research data management profession. Materials and Methods: Based on prior work developing and maintaining a practice standard and professional certification exam, a survey was administered to a captive group of clinical research data managers to assess professional competencies, types of data managed, types of studies supported, and necessary foundational knowledge. Results: Respondents confirmed a set of 91 professional competencies. As expected, differences were seen in job tasks between early- to mid-career and mid- to late-career practitioners. Respondents indicated growing variability in types of studies for which they managed data and types of data managed. Discussion: Respondents adapted favorably to the separate articulation of professional competencies vs foundational knowledge. The increases in the types of data managed and variety of research settings in which data are managed indicate a need for formal education in principles and methods that can be applied to different research contexts (ie, formal degree programs supporting the profession), and stronger links with the informatics scientific discipline, clinical research informatics in particular. Conclusion: The results document the scope of the profession and will serve as a foundation for the next revision of the Certified Clinical Data ManagerTM exam. A clear articulation of professional competencies and necessary foundational knowledge could inform the content of graduate degree programs or tracks in areas such as clinical research informatics that will develop the current and future clinical research data management workforce.

The performance of a novel neutralizer for space applications based on a ExB discharge is presented. Preliminary tests were carried out with argon gas and flow rates in the range of 5-10 SCCM. Electrons were extracted through an orifice of diameter 1.8 mm. The maximum extracted current versus input power reported was 2.4 mA/W. The total power input, given by the sum of discharge power plus the extraction power, was in the range of 40-90 W. During extraction tests, the discharge current was limited at 0.2 A due to limit in the cooling system. Future work will be focused on tests at various extraction orifice diameters and cathode materials. Ultimately, xenon and non-conventional gases would be tested as working gases.

Die im internationalen Vergleich schwache Innovationskraft stellt eine groβe Herausforderung fur die deutsche Bankwirtschaft dar. Mit Crowdsourcing, das die Auslagerung einer Unternehmensaufgabe an ein groβes, unbestimmtes Netzwerk beschreibt, findet ein neues, internetbasiertes Instrument inzwischen auch erste Anwendungen bei Finanzdienstleistern. Denn Crowdsourcing bietet neue Losungspotenziale zur Starkung der Innovationskraft. Die Analyse findet allerdings nur eine begrenzte Zahl an Anwendungen zum Crowdsourcing im Finanzsektor. Ein Groβteil der Banken hat offenbar noch Vorbehalte, nur wenige haben in Vorreiterrollen Crowdsourcing erfolgreich implementiert. Beispiele wie das Crowd Funding, das auf die Investitionsbereitschaft der Crowd abzielt, oder verschiedene Plattformen, bei denen das Talent der Crowd zur Filterung der Besten aus den Vielen ausgenutzt wird, zeigen aber, dass Crowdsourcing in vielen Bereichen des Finanzmarkts nicht nur moglich ist, sondern auch sehr erfolgreich genutzt werden kann.

Markku Kaste ja Filip Scheperjans työryhmän jäsenenä. Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP 90, 60-90, and Outcomes: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Results: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitations: Generalizability issues arising from a clinical trial population. Conclusions: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs. Am J Kidney Dis. 68(1): 94-102. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license.

The relaxation behavior of the glass process of the polystyrene (PS) phase in three different types of block copolymers has been investigated. Four triblock copolymers are used, namely, two styrene–butadiene–styrene (S–B–S), styrene–styrene butadiene–styrene (S–SB–S) and styrene–ethylene butylene–styrene (S–EB–S). The materials were crosslinked by means of dicumylperoxide (DCUP) with concentrations up to 10 phr, i.e. 10 g of DCUP per 100 g of the polymer. Dynamic mechanical measurements have been done for the complex shear compliance in wide temperature and frequency windows, 30–150 °C and 10−3–10 Hz, respectively. Complete master curves have been constructed for all samples and analyzed using Cole–Cole function. It is observed that crosslinking reduces the relaxation strength of the low frequency process much more than that of the high frequency process. Therefore, the glass relaxation process of the PS-phase can be easily detected in the crosslinked samples. The relaxation frequency of the maximum of the glass relaxation process of the PS-phase is found to be independent of the crosslinking concentration. The relaxation behavior of block copolymers with respect to crosslinking is compared to styrene butadiene rubber (SBR) statistical copolymer. A method to detect the glass transition temperature (Tg) of the investigated block copolymers is suggested.

Many attempts to upgrade polystyrene have been made in the past. One of the last and most popular examples is the upgrading of polystyrene by stereo-controlled polymerization of styrene monomer, yielding a syndiotactic material. But the property profile of polystyrene can also be improved by stiffening the polymer chain with bulky groups. 1,1-Diphenylethylene (DPE) was selected as a monomer with such a bulky group and was copolymerized anionically with styrene to give an amorphous copolymer with a statistical chain structure which was called 'super-polystyrene'. In this paper the conditions of the anionic polymerization and the properties of the resulting materials are described. Depending on the DPE content, the glass transition temperature can be varied from 104°C to 180°C. Up to a DPE content of 15%, these styrene-DPE copolymers are miscible with GPPS as well as with syndiotactic polystyrene. Toughening of the transparent polymers was achieved with glass fibers and grafted rubber particles. Block copol...

The mouse hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Addition of extracellular glutamate depletes the cells of glutathione (GSH) by blocking the glutamate-cystine antiporter system x(c)(-). GSH is the main antioxidant in neurons and its depletion induces a well-defined program of cell death called oxytosis, which is probably synonymous with the iron-dependent form of non-apoptotic cell death termed ferroptosis. Oxytosis is characterized by an increase of reactive oxygen species and a strong calcium influx preceding cell death. We found a significant reduction in store-operated calcium entry (SOCE) in glutamate-resistant HT22 cells caused by downregulation of the Ca(2+) channel ORAI1, but not the Ca(2+) sensors STIM1 or STIM2. Pharmacological inhibition of SOCE mimicked this protection similarly to knockdown of ORAI1 by small interfering RNAs. Long-term calcium live-cell imaging after induction of the cell death program showed a specific reduction in Ca(2+)-positive cells by ORAI1 knockdown. These results suggest that dysregulated Ca(2+) entry through ORAI1 mediates the detrimental Ca(2+) entry in programmed cell death induced by GSH depletion. As this detrimental Ca(2+) influx occurs late in the course of the cell death program, it might be amenable to therapeutic intervention in diseases caused by oxidative stress.

Protecting the health of the athlete is the primary goal of the International Olympic Committee’s Medical Commission. One of its main objectives is the promotion of safe practices in the training of the elite child athlete. The elite child athlete is one who has superior athletic talent, undergoes specialised training, receives expert coaching and is exposed to early competition. Sport provides a positive environment that may enhance the physical growth and psychological development of children. This unique athlete population has distinct social, emotional and physical needs, which vary depending on the athlete’s particular stage of maturation. The elite child athlete requires appropriate training, coaching and competition that ensure a safe and healthy athletic career and promote future well-being. This document reviews the scientific basis of sports training in the child, the special challenges and unique features of training elite children and provides recommendations to parents, coaches, healthcare providers, sports governing bodies and other parties concerned. Aerobic and anaerobic fitness and muscle strength increase with age, growth and maturation. Improvement in these variables is asynchronous. Children experience more marked improvements in anaerobic and strength performance than in aerobic performance during pubescence. Boys’ aerobic and anaerobic fitness and muscle strength are …

HIV-1 B is predominant in Brazil, but HIV-1 C has increasingly been reported in the south of the country. However, many samples clustering with clade C are actually a recombinant, with a small B segment at RT (CRF31). Samples (209) from the three cities with the highest aids prevalence rate are analyzed. Partial polymerase sequences from HIV RNA made it possible to determine HIV clades and recombination patterns and to identify primary drug resistance mutations (DRMs). The incidence was estimated with a BED assay. HIV-1 C and CRF31 patterns were twice as frequent as clade B at all sites, but the proportion of C and CRF31 patterns was significantly different among sites. The incidence estimate for SC was 2.6 persons-years. Infection in recent or younger cases showed no association with clade C. Surveillance DRM was observed in 8.3% (95% CI 5-13), mostly to NNRTIs. Clade F pol genomes had significantly more primary DRM.

The report discusses a project to develop a low-emissions natural gas engine with exhaust gas recirculation (EGR) and a three-way catalyst (TWC).

The reaction of peptide Gly-Ala-Phe with the alpha-dicarbonyl compounds glyoxal and methylglyoxal was studied under physiological conditions (pH=7.4, 37 degrees C). Using HPLC with UV and fluorescence detection, a rapid derivatization of the peptide and the concomitant formation of well-defined products were observed. The products, which showed characteristic UV absorbance (lambda(max)=320 to 340 nm) and fluorescence (lambda(ex)=330 to 340 nm, lambda(em)=395 to 405 nm), were identified by ESI-MS and NMR spectroscopic analysis as the N-terminally pyrazinone-modified peptides I (N-[2-(2-oxo-2H-pyrazin-1-yl)-propyl]-phenylalanine) and II (N-[2-(5-methyl-2-oxo-2H-pyrazin-1-yl)-propionyl]-phenylalanine). Model experiments revealed that the reactivity of the N-termini of peptides towards a derivatization by glyoxal is in the same order of magnitude as that of arginine, which generally is attributed as main target for alpha-dicarbonyl compounds in proteins. Incubation of insulin with glyoxal proved the protein-bound formation of pyrazinones, with the N-terminus of the B-chain as the main target. According to these results, we conclude that N-terminal pyrazinones represent a new type of advanced glycation end-products (AGEs) with significance for biological systems and foods.

This project explored a new concept for high-pressure xenon ionization chambers by replacing the Frisch grid with coplanar grid electrodes similar to those used in wide bandgap semiconductor gamma-ray spectrometers. This work is the first attempt to apply the coplanar grid anode design in a gas ionization chamber in order to achieve to improved energy resolution. Three prototype detectors, two cylindrical and one parallel plate configurations, were built and tested. While the detectors did not demonstrate energy resolutions as good as other high pressure xenon gamma-ray spectrometers, the results demonstrated that the concept of single polarity charge sending using coplanar grid electrodes will work in a gas detector.

Impaired wound healing is characteristic of diabetic patients. Potential reasons include poor inflammatory response, granulation tissue formation, and abnormal patterns of cytokine release and response. Vascular endothelial growth factor, abnormally regulated during healing in diabetics, is the major factor stimulating angiogenesis during normal wound healing. We tested our hypothesis that topically applied vascular endothelial growth factor would improve wound closure rates in diabetic animals in a full-thickness wound model in genetically diabetic mice (C57 BL/KsJ db/db). Animals received either 1.0 µg of vascular endothelial growth factor165 or polyethylene glycol alone topically to wounds daily between days 0 and 4 postwounding. Wound area was measured at days 0, 5, 10, 15, and 21. Data were analyzed using probit analysis and expressed as length-of-time (LT) to 50, 90, and 95% wound closure. Among untreated animals, nondiabetics had an LT50 of 8.5 days (fiducial limits 8.3–8.7), while diabetics had an LT50 of 15.8 days (15.6–16.1). Vascular endothelial growth factor-treated animals had LT50 values of 7.8 (7.6–8.1) and 11.8 days (11.6–12.0) for nondiabetics and diabetics, respectively, representing a 25% improvement in time to 50% closure in treated diabetics. We conclude that topically applied vascular endothelial growth factor improves time to wound closure in the genetically diabetic mouse model. (WOUND REP REG 2003;11:127–131)

International teamwork is one of the core components of network organizations. A set of studies was conducted to observe how students learned to work in globally dispersed virtual teams. Nineteen teams of three to seven graduate students, who resided in 13 different universities in nine different countries, were observed for five weeks. Many teams had members separated by a 16-hour time difference. Students were challenged to push the limits of electronic mail by collaborating on unstructured tasks with people they would never meet face-to-face. Students learned a variety of collaboration, socialization, and global communication skills while accomplishing difficult work. >

In search for a new therapeutic approach for metastasized renal cell carcinoma (RCC), we evaluated the cytotoxicity of a novel prodrug chemoimmunoconjugate with monoclonal antibody (mAb) 138H11 and the DNA-cleaving enediyne calicheamicin thetaI1 (Camtheta) in vitro and in vivo. Previously, mAb 138H11, produced against human renal gamma-glutamyltransferase, stained over 99% clear cell and papillary RCC on frozen sections, showing a membranous expression of the target antigen. In contrast, in normal kidneys gammaGT was restricted to the brush-border in the lumen of proximal tubules and not accessible to the circulation. Thus, human tumor-bearing kidneys perfused in an extra-corporeal system with 99mTc-138H11 revealed a high, specific uptake into the tumor. In this study, fluorescence-activated cell sorting analysis showed binding of mAb 138H11 to RCC cell lines, whereas squamous cell carcinoma lines, fibroblasts, and the murine RENCA were negative. XTT cell proliferation assays revealed efficient killing of the Caki-1 cell line by the 138H11-Camtheta conjugate using SPDP (EC50 = 5 x 10(-11) M) as a covalent linker. For in vivo testing, five groups of eight nude mice each were injected with 2.5 x 10(6) Caki-1 cells s.c. and treated with the following: (a) PBS; (b) 138H11; (c) Camtheta; (d) a mixture of 138H11 and Camtheta; and (e) 138H11-Camtheta conjugate. Treatment started on day 1 after tumor induction and was repeated three times. The data show a highly significant inhibition of tumor growth with the 138H11-Camtheta conjugate versus PBS (P = 0.004). Only mice treated with 138H11-Camtheta showed a tumor shrinkage to minimal residues. In a second experiment, lower doses of the 138H11-Camtheta conjugate were compared with an antineuroblastoma mAb (ch14.18), confirming targeted killing of RCC by the 138H11-Camtheta conjugate at tolerable toxicity in vivo. In conclusion, these combined results encourage further studies for targeted therapy of metastatic RCC with mAb 138H11 conjugates.

The diuretic amiloride has been reported to inhibit both Na+–H+ antiport and the urokinase-type plasminogen activator. As a consequence of these inhibitions, neovascularization may also be inhibited. We hypothesized that if amiloride could be effectively delivered in a site-specific manner, a system might be developed that could inhibit localized angiogenesis. In order to evaluate this possibility we conducted a study that compared two different controlled-release systems into which amiloride had been incorporated. The effectiveness of amiloride release from each delivery system was determined by quantitating angiogenic patterns in a chick chorioallantoic membrane (CAM) system using a fractal analysis software program. The two delivery systems compared were sucrose acetate isobutyrate (SAIB) and calcium alginate. Initial HPLC laboratory tests confirmed that amiloride could be released from both SAIB and calcium alginate in vitro in a sustained manner for 72 h. The CAM studies confirmed that neither SAIB nor calcium alginate alone promoted or inhibited angiogenesis when compared to nontreated controls. The release of amiloride from each delivery vehicle resulted in a significant (P < 0.05) inhibition of angiogenesis following both 24 and 48 h of release compared to controls. There was no difference in inhibition of angiogenesis, however, when comparing SAIB + amiloride treated CAMs with calcium alginate + amiloride treated CAMs. These data suggest that both SAIB and calcium alginate may be useful delivery vehicles for the localized application of amiloride to control angiogenesis. Such a system could potentially control tumor angiogenesis without systemic effects.

Anionic copolymerization of 1,1-diphenylethylene (DPE) and styrene yields random copolymers containing a molar excess of styrene units or alternating polymers. Depending on the DPE content their glass transition temperature can be as high as 180°C. The toughness of the brittle copolymers can be enhanced with grafted rubber particles. Block copolymerization with minor amounts of butadiene yields tough and transparent materials. Thermoplastic elastomers with an enhanced softening point having the block sequence S/DPE-b-Bu-b-S/DPE and S/DPEb-EB-b-S/DPE are presented.