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Copyright of Bautechnik is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Healthcare providers may experience moral distress when they are unable to take the ethically or morally appropriate action due to real or perceived constraints in delivering care, and this psychological stressor can negatively impact their mental health, leading to burnout and compassion fatigue. This study describes healthcare providers experiences of moral distress working in long-term care settings during the COVID-19 pandemic and measures self-reported levels of moral distress pre- and post-implementation of the Dementia Isolation Toolkit (DIT), a person-centred care intervention designed for use by healthcare providers to alleviate moral distress. Methods: Subjective levels of moral distress amongst providers (e.g., managerial, administrative, and front-line employees) working in three long-term care homes was measured pre- and post-implementation of the DIT using the Moral Distress in Dementia Care Survey and semi-structured interviews. Interviews explored participants' experiences of moral distress in the workplace and the perceived impact of the intervention on moral distress. Results: A total of 23 providers between the three long-term care homes participated. Following implementation of the DIT, subjective levels of moral distress measured by the survey did not change. When interviewed, participants reported frequent experiences of moral distress from implementing public health directives, staff shortages, and professional burnout that remained unchanged following implementation. However, in the post-implementation interviews, participants who used the DIT reported improved self-awareness of moral distress and reductions in the experience of moral distress. Participants related this to feeling that the quality of resident care was improved by integrating principals of person-centered care and information gathered from the DIT. Conclusions: This study highlights the prevalence and exacerbation of moral distress amongst providers during the pandemic and the myriad of systemic factors that contribute to experiences of moral distress in long-term care settings. We report divergent findings with no quantitative improvement in moral distress post-intervention, but evidence from interviews that the DIT may ease some sources of moral distress and improve the perceived quality of care delivered. This study demonstrates that an intervention to support person-centred isolation care in this setting had limited impact on overall moral distress during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Polyurethane (PU) foams are created via the chemical reactions arising after the blending of two initially liquid components (polyols and isocyanates). They are widely used for thermal insulation, for which a small pore size is required. Some of the most efficient pore size–reducing agents have proven to be per- and polyfluorinated carbons (FCs) which are simply added in small quantities to the initially liquid mixture. However, despite their long-standing use, their modes of action have only recently begun to be studied in detail. One widely accepted explanation of their action is that they supposedly suppress diffusional gas exchange between bubbles in the liquid-foam state of the nascent PU foam (foam coarsening). However, using a new double-syringe mixing technique, we show that FCs actually act at a much earlier state of the process: they facilitate the entrainment of tiny air bubbles into PU foam systems during the initial blending process. These bubbles serve as sites for heterogeneous nucleation during the foaming process, and their large number leads to a significant reduction of the characteristic pore size. More importantly, we also demonstrate that the same overall relation is found between the air bubble density and the final pore size for systems with and without FC. Combined with a detailed analysis of the pore size distribution, we argue that the main pore size–reducing effect of FCs is to facilitate air entrainment and that foam aging–related effects only play a minor role. [ABSTRACT FROM AUTHOR]

The use of mobile head CT scanners in the neurointensive care unit (NICU) saves time for patients and NICU staff and can reduce transport-related mishaps, but the reduced image quality of previous mobile scanners has prevented their widespread clinical use. This study compares the image quality of SOMATOM On.Site (Siemens Healthineers, Erlangen, Germany), a state-of-the-art mobile head CT scanner, and a conventional 64-slice stationary CT scanner. The study included 40 patients who underwent head scans with both mobile and stationary scanners. Gray and white matter signal and noise were measured at predefined locations on axial slices, and signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated. Artifacts below the cranial calvaria and in the posterior fossa were also measured. In addition, image quality was subjectively assessed by two radiologists in terms of corticomedullary differentiation, subcalvarial space, skull artifacts, and image noise. Quantitative measurements showed significantly higher image quality of the stationary CT scanner in terms of noise, SNR and CNR of gray and white matter. Artifacts measured in the posterior fossa were higher with the mobile CT scanner, but subcalvarial artifacts were comparable. Subjective image quality was rated similarly by two radiologists for both scanners in all domains except image noise, which was better for stationary CT scans. The image quality of the SOMATOM On.Site for brain scans is inferior to that of the conventional stationary scanner, but appears to be adequate for daily use in a clinical setting based on subjective ratings. [ABSTRACT FROM AUTHOR]

Background. Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods. We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan–Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results. The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001 ; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001 ; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P = 0.02 ; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P = 0.04 ; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P = 0.02 ; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P = 0.01 ; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion. Young age seems to positively influence patients' survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections (PJI) are serious complications after arthroplasty, associated with high morbidity, mortality, and complex treatment processes. The outcomes of different PJI entities are largely unknown. The aim of this study was to access the early outcomes of different PJI entities. A retrospective, single-center study was conducted. The characteristics and outcomes of patients with PJI treated between 2018 and 2019 were evaluated 12 months after the completion of treatment. Primary endpoints were mortality, relapse free survival (RFS) and postoperative complications (kidney failure, sepsis, admission to ICU). A total of 115 cases were included [19.1% early (EI), 33.0% acute late (ALI), and 47.8% chronic infections (CI)]. Patients with ALI were older (p = 0.023), had higher ASA scores (p = 0.031), preoperative CRP concentrations (p = 0.011), incidence of kidney failure (p = 0.002) and sepsis (p = 0.026). They also tended towards higher in-house mortality (ALI 21.1%, 13.6% EI, 5.5% CI) and admission to ICU (ALI 50.0%, 22.7% EI, 30.9% CI). At 12 months, 15.4% of patients with EI had a relapse, compared to 38.1% in ALI and 36.4% in CI. There are differences in patient characteristics and early outcomes between PJI entities. Patients with EI have better early clinical outcomes. Patients with ALI require special attention during follow-up because they have higher occurrences of relapses and postoperative complications than patients with EI and CI. [ABSTRACT FROM AUTHOR]

In this study, the flow fields of two‐stage impellers, consisting of combinations of different impeller types on one shaft, are investigated using stereo particle image velocimetry. Based on the results of torque measurements, diameters for different impellers are determined in order to achieve matching power input of the individual turbines. When implemented adequately, both selected impellers are able to contribute their respective characteristics, resulting in flow fields that differ significantly from those induced by single‐stage impellers as well as two‐stage setups consisting of identical impellers. [ABSTRACT FROM AUTHOR]

Despite the long-standing use of per- and polyfluorinated carbons (FCs) as pore size–reducing agents for polyurethane rigid (PUR) foams, their mechanisms of action remain poorly understood. To shed light on these mechanisms, we provide a quantitative analysis of the influence of the FC concentration on the pore size of PUR cup foams of two different model PUR foam systems: an industrially-relevant "technical system" and a simplified "scientific system." Combining scanning electron microscopy (SEM) and the PORE!SCAN method, we provide a detailed analysis of the pore size distributions of the obtained foams. We confirm that the characteristic pore size of both systems is indeed significantly reduced by adding small quantities of FC. However, we show that there seems to exist a critical FC concentration (about 3 wt.% with respect to the A-component) beyond which adding more FC has a negligible effect. More interestingly, the relative extent of the pore size reduction is almost identical for both PUR foam systems and the normalized pore size distributions remain largely unchanged over the whole range of FC concentrations. Our findings suggest that the FC-driven pore size reduction is a general effect caused by distinct mechanisms that are independent of the choice of the PUR foam system. Moreover, we hypothesize that this effect is not to be searched for during foam aging, as often reported, but during the pre-mixing step. [ABSTRACT FROM AUTHOR]

The interest in polyurethane rigid (PUR) foams as potent thermally insulating materials for a wide range of applications continues to grow as the minimization of CO2 emissions has become a global issue. Controlling the thermal insulation efficiency of PUR foams starts with the control of their morphology. Although the presence of micrometric air bubbles originating from air entrainment during the blending of the PU reactive mixture has been shown to influence the final PUR foam morphology, detailed experimental investigations on how exactly they affect the final PUR foam pore size are still lacking. To fill this gap, we use a double-syringe mixing device, which allows to control the number of air bubbles generated during a first air entrainment step, before using the same device to blend the reactive components in a sealed environment, avoiding further air entrainment. Keeping all experimental parameters constant except for the air bubble density in the reactive mixture, we can correlate changes of the final PUR foam morphology with the variation of the air bubble density in the initially liquid reactive mixture. Our results confirm recent findings which suggest the presence of two different regimes of bubble nucleation and growth depending on the presence or absence of dispersed air bubbles in the liquid reactive mixture. Our study pushes those insights further by demonstrating an inverse relation between the air bubble density in the liquid reactive mixture and the final pore volume of the PUR foam. For example, at constant chemical formulation and blending conditions, we could vary the final pore size between 400–1600 μm simply by controlling the amount of pre-dispersed air bubbles within the system. We are confident that the presented approach may not only provide a valuable model experiment to scan formulations in R&D laboratories, but it may also provide suggestions for the optimization of industrial processes. [ABSTRACT FROM AUTHOR]

Bilateral absence of the superior vena cava is associated with rhythm and structural abnormalities and is diagnosed incidentally either during imaging procedures or venous catheterization or pacemaker implantation. Knowledge of this entity is important to allow proper referral, medical management of its associated abnormalities, and risk reduction in certain interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Ewing sarcoma (EwS) is a malignant bone and soft-tissue cancer that primarily affects adolescents and young adults. In rare cases, EwS develops as a secondary cancer; that is, after a previous cancer other than EwS. We collected information on all patients with EwS as a secondary cancer from three past international EwS studies to better understand affected patients and to identify potential at-risk patients. Forty-two patients with secondary EwS were identified, representing approximately 1.1% of all EwS cases. As primary cancers, patients suffered mainly from cancers of the blood-forming system, such as leukemia and lymphoma. We could not identify any risk factors for the development of EwS as a secondary cancer. Survival from a second cancer diagnosis with EwS is comparable to EwS as a first cancer diagnosis; therefore, patients with secondary EwS should also be offered complete therapy with the goal of cure, especially if the tumor is localized to only one site. Ewing sarcoma (EwS) is the second most common bone and soft tissue tumor, affecting primarily adolescents and young adults. Patients with secondary EwS are excluded from risk stratification in several studies and therefore do not benefit from new therapies. More knowledge about patients with EwS as secondary malignant neoplasms (SMN) is needed to identify at-risk patients and adapt follow-up strategies. Epidemiology, clinical characteristics, and survival analyses of EwS as SMN were analyzed in 3844 patients treated in the last three consecutive international EwS trials, EICESS 92, Euro-E.W.I.N.G. 99, and EWING 2008. Forty-two cases of EwS as SMN (approximately 1.1% of all patients) were reported, preceded by a heterogeneous group of malignancies, mainly acute lymphoblastic leukemias (n = 7) and lymphomas (n = 7). Three cases of EwS as SMN occurred in the presumed radiation field of the primary tumor. The median age at diagnosis of EwS as SMN was 19.4 years (range, 5.9–72) compared with 10.8 years (range, 0.9–51.2) for primary EwS. The median interval between first malignancy and EwS diagnosis was 7.4 years. The 3-year overall survival (OS)/event-free survival (EFS) was 0.69 (SE = 0.09)/0.53 (SE = 0.10) for localized patients and 0.36 (SE = 0.13)/0.29 (SE = 0.12) for metastatic patients (OS: p = 0.02; EFS: p = 0.03). Survival in patients with EwS as SMN did not differ between hematologic or solid primary malignancies. EwS as SMN is rare; however, survival is similar to that of primary EwS, and its risk-adjusted treatment should be curative, especially in localized patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Ewing sarcoma (EwS) is a malignant bone and soft tissue cancer that requires intensive treatment with multiple chemotherapies and either surgery, irradiation, or both as local therapy. For most survivors of EwS, long-term sequelae such as secondary malignant neoplasms (SMNs) other than EwS are concerning. Few studies suggest that SMNs after EwS are a rare but serious event. Comprehensive data are lacking. We reviewed consecutive EwS trials from the Cooperative Ewing Sarcoma Study (CESS) group to evaluate the features of SMNs in EwS patients. Our analysis revealed 101 cases of SMNs in 96 EwS patients. Solid SMNs were detected more frequently than hematologic SMNs, in 55.2% versus 44.8%. The latency between EwS diagnosis and SMN occurrence was longer for solid SMNs (median: 8.4 years) than for hematologic SMNs (median: 2.4 years) (p < 0.001). The survival rate after SMNs was 0.49, with solid SMNs having a significantly better prognosis. Our results confirm the need for a structured follow-up system. Ewing sarcoma (EwS) represents highly aggressive bone and soft tissue tumors that require intensive treatment by multi-chemotherapy, surgery and/or radiotherapy. While therapeutic regimens have increased survival rates, EwS survivors face long-term sequelae that include secondary malignant neoplasms (SMNs). Consequently, more knowledge about EwS patients who develop SMNs is needed to identify high-risk patients and adjust follow-up strategies. We retrospectively analyzed data from 4518 EwS patients treated in five consecutive EwS trials from the Cooperative Ewing Sarcoma Study (CESS) group. Ninety-six patients developed SMNs after primary EwS, including 53 (55.2%) with solid tumors. The latency period between EwS and the first SMN was significantly longer for the development of solid SMNs (median: 8.4 years) than for hematologic SMNs (median: 2.4 years) (p < 0.001). The cumulative incidence (CI) of SMNs in general increased over time from 0.04 at 10 years to 0.14 at 30 years; notably, the specific CI for hematologic SMNs remained stable over the different decades, whereas for solid SMNs it gradually increased over time and was higher for metastatic patients than in localized EwS patients (20 years: 0.14 vs. 0.06; p < 0.01). The clinical characteristics of primary EwS did not differ between patients with or without SMNs. All EwS patients received multi-chemotherapy with adjuvant radiotherapy in 77 of 96 (80.2%) patients, and the use of radiation doses ≥ 60 Gy correlated with the occurrence of SMNs. The survival rate after SMNs was 0.49, with a significantly better outcome for solid SMNs compared with hematologic SMNs (3 years: 0.70 vs. 0.24, respectively; p < 0.001). The occurrence of SMNs after EwS remains a rare event but requires a structured follow-up system because it is associated with high morbidity and mortality. [ABSTRACT FROM AUTHOR]

Simple Summary: The main oncogene in Ewing sarcoma directly drives a high expression of a previously unknown variant KCNN1 (encoding the KCa2.1 channel) that we also verified in samples from >200 patients. Yet, we found that the channel is not functional and does not modulate Ewing sarcoma cell behavior. We could explain this lack of functional impact by the surprising absence of any KCa2.1-carried K+ current in Ewing sarcoma cells. However, we show in a proof-of-principle study that the essential lack of a K+ conductance can be exploited by applying hypoosmotic stress and effectively and selectively killing the Ewing sarcoma cells. Ewing sarcoma (EwS) is a rare and highly malignant bone tumor occurring mainly in childhood and adolescence. Physiologically, the bone is a central hub for Ca2+ homeostasis, which is severely disturbed by osteolytic processes in EwS. Therefore, we aimed to investigate how ion transport proteins involved in Ca2+ homeostasis affect EwS pathophysiology. We characterized the expression of 22 candidate genes of Ca2+-permeable or Ca2+-regulated ion channels in three EwS cell lines and found the Ca2+-activated K+ channel KCa2.1 (KCNN1) to be exceptionally highly expressed. We revealed that KCNN1 expression is directly regulated by the disease-driving oncoprotein EWSR1-FL1. Due to its consistent overexpression in EwS, KCNN1 mRNA could be a prognostic marker in EwS. In a large cohort of EwS patients, however, KCNN1 mRNA quantity does not correlate with clinical parameters. Several functional studies including patch clamp electrophysiology revealed no evidence for KCa2.1 function in EwS cells. Thus, elevated KCNN1 expression is not translated to KCa2.1 channel activity in EwS cells. However, we found that the low K+ conductance of EwS cells renders them susceptible to hypoosmotic solutions. The absence of a relevant K+ conductance in EwS thereby provides an opportunity for hypoosmotic therapy that can be exploited during tumor surgery. [ABSTRACT FROM AUTHOR]

Despite the incredible complexity of our brains' neural networks, theoretical descriptions of neural dynamics have led to profound insights into possible network states and dynamics. It remains challenging to develop theories that apply to spiking networks and thus allow one to characterize the dynamic properties of biologically more realistic networks. Here, we build on recent work by van Meegen and Lindner who have shown that "rotator networks," while considerably simpler than real spiking networks and, therefore, more amenable to mathematical analysis, still allow one to capture dynamical properties of networks of spiking neurons. This framework can be easily extended to the case where individual units receive uncorrelated stochastic input, which can be interpreted as intrinsic noise. However, the assumptions of the theory do not apply anymore when the input received by the single rotators is strongly correlated among units. As we show, in this case, the network fluctuations become significantly non-Gaussian, which calls for reworking of the theory. Using a cumulant expansion, we develop a self-consistent analytical theory that accounts for the observed non-Gaussian statistics. Our theory provides a starting point for further studies of more general network setups and information transmission properties of these networks. [ABSTRACT FROM AUTHOR]

Background: Neonatal stroke remains a rare condition that has not yet been assessed in the field of endovascular treatment. Case: We present the first case report of a successful mechanical thrombectomy in a newborn with a basilar occlusion the treatment was 14 hours after birth. Complete reperfusion of the basilar artery was achieved after the two thrombectomy maneuvers with stent retrievers. Imaging follow-up proved patency of the target vessel and at day 30, the patient showed no neurologic deficits. Conclusions: Mechanical thrombectomy appears to be technically feasible and can be an individual option in selected cases to treat stroke in neonates with proven persistent proximal cerebral artery occlusion. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to integrate research on competitive and cooperative repertoires and to simultaneously assess the direct, indirect and curvilinear effects of competitive and cooperative action repertoires in relation to firm performance. Design/methodology/approach: The analyses are conducted using a longitudinal dual-industry sample of publicly traded firms, including over 6,500 competitive actions and 750 cooperative actions. The authors use fixed effects (FE) regression models to test the diminishing returns of action volume on firm performance as well as the moderating effects of action diversity. Findings: The results suggest that increasing competitive and cooperative actions yields diminishing returns in relation to firm performance. Furthermore, in the context of competitive action repertoire diversity, increased diversity magnifies the diminishing returns of competitive action volume on firm performance. Originality/value: The study provides a firm-level conceptualization of overall competitive and cooperative repertoires to extend the literature on competition and cooperation beyond dyadic interactions or structural determinants of competitive and cooperative actions. [ABSTRACT FROM AUTHOR]

Background: A wide range of mortality rates has been reported in COVID-19 patients on the intensive care unit. We wanted to describe the clinical course and determine the mortality rate in our institution's intensive care units. Methods: To this end, we performed a retrospective cohort study of 50 COVID-19 patients admitted to the ICU at a large German tertiary university hospital. Clinical features are reported with a focus on ICU interventions, such as mechanical ventilation, prone positioning and extracorporeal organ support. Outcome is presented using a 7-point ordinal scale on day 28 and 60 following ICU admission. Results: The median age was 64 years, 78% were male. LDH and D-Dimers were elevated, and patients were low on Vitamin D. ARDS incidence was 75%, and 43/50 patients needed invasive ventilation. 22/50 patients intermittently needed prone positioning, and 7/50 required ECMO. The interval from onset of the first symptoms to admission to the hospital and to the ICU was shorter in non-survivors than in survivors. By day 60 after ICU admission, 52% of the patients had been discharged. 60-day mortality rate was 32%; 37% for ventilated patients, and 42% for those requiring both: ventilation and renal replacement therapy. Conclusions: Early deterioration might be seen as a warning signal for unfavourable outcome. Lung-protective ventilation including prone positioning remain the mainstay of the treatment. [ABSTRACT FROM AUTHOR]

Existing research suggests that peace is more stable after military victories than it is after peace agreements. This article challenges this conventional wisdom. By applying survival analysis, we demonstrate that peace agreements exhibit just as strong of a relationship to enduring peace as military victories do. Moreover, we investigate the assumptions that underpin the aforementioned claim. These assumptions link peace survival to the type of civil war termination and refer to intervening variables. Using time-series data for 48 civil wars that ended between 1990 and 2009, the empirical analysis finds support for only two underpinning assumptions in favour of victories. [ABSTRACT FROM AUTHOR]

Premise: Apomixis (asexual reproduction by seed, spore, or egg) has evolved repeatedly across the tree of life. Studies of animals and angiosperms show that apomictic lineages are often evolutionarily short‐lived and frequently exhibit different distributions than their sexual relatives. However, apomixis is rare in these groups. Less is known about the role of apomixis in the evolution and biogeography of ferns, in which ~10% of species are apomictic. Apomixis is especially common in the fern genus Pteris (34–39% of species); however, because of the limited taxonomic and geographic sampling of previous studies, the true frequency of apomixis and its associations with geography and phylogeny in this lineage remain unclear. Methods: We used spore analyses of herbarium specimens to determine reproductive mode for 127 previously unsampled Pteris species. Then we leveraged biogeographic and phylogenetic analyses to estimate the global distribution and evolution of apomixis in Pteris. Results: Among all Pteris species examined, we found that 21% are exclusively apomictic, 71% are exclusively sexual, and 8% have conflicting reports. Apomixis is unevenly distributed across the range of the genus, with the Paleotropics exhibiting the highest frequency, and has evolved numerous times across the Pteris phylogeny, with predominantly East Asian and South Asian clades containing the most apomictic species. Conclusions: Apomixis arises frequently in Pteris, but apomictic species do not appear to diversify. Species that encompass both apomictic and sexual populations have wider ranges than exclusively sexual or apomictic species, which suggests that sexual and apomictic ferns could occupy separate ecological niches. [ABSTRACT FROM AUTHOR]

Background: Institution-specific guidelines (ISGs) within the framework of antimicrobial stewardship programs offer locally tailored decision support taking into account local pathogen and resistance epidemiology as well as national and international guidelines. Objectives: To assess the impact of ISGs for antimicrobial therapy on antibiotic consumption and subsequent changes in resistance rates and Clostridioides difficile infections (CDIs). Methods: The study was conducted at the Leipzig University Hospital, a 1,451-bed tertiary-care medical center, and covered the years 2012 to 2020. Since 2014, ISGs were provided to optimize empirical therapies, appropriate diagnostics, and antimicrobial prophylaxis. We used interrupted time series analysis (ITSA) and simple linear regression to analyze changes in antimicrobial consumption, resistance and CDIs. Results: Over the study period, 1,672,200 defined daily doses (DDD) of antibiotics were dispensed, and 85,645 bacterial isolates as well as 2,576 positive C. difficile cultures were collected. Total antimicrobial consumption decreased by 14% from 2012 to 2020, without clear impact of the deployment of ISGs. However, implementation of ISGs was associated with significant decreases in the use of substances that were rarely recommended (e.g., fluoroquinolones). Over the whole study period, we observed declining resistance rates to most antibiotic classes of up to 25% in Enterobacterales, staphylococci, and Pseudomonas aeruginosa. Switching from ceftriaxone to cefotaxime was associated with reduced resistance to third-generation cephalosporins. The number of CDI cases fell by 65%, from 501 in 2012 to 174 in 2020. Conclusions: Well-implemented ISGs can have a significant, immediate, and lasting impact on the prescription behavior. ISGs might thereby contribute to reduce resistance rates and CDI incidences in the hospital setting. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia is an important nosocomial pathogen in immunocom-promised individuals and characterized by intrinsic resistance to broad-spectrum antibacterial agents. Limited data exists on its clinical relevance in immunocompromised pediatric patients, particularly those with hematological or oncological disorders. In a retrospective single center cohort study in pediatric patients receiving care at a large european pediatric hematology and oncology department, ten cases of invasive S.maltophilia infections (blood stream infections (BSI), 4; BSI and pneumonia, 3, or soft tissue infection, 2; and pneumonia, 1) were identified between 2010 and 2020. Seven patients had lymphoblastic leukemia and/or were post allogeneic hematopoietic cell transplantation. Invasive S.maltophilia infections occurred in a setting of indwelling central venous catheters, granulocytopenia, defective mucocutaneous barriers, treatment with broad-spectrum antibacterial agents, and admission to the intensive care unit. Whole genome sequencing based typing revealed no genetic relationship among four individual S.maltophilia isolates. The case fatality rate and mortality at 100 days post diagnosis were 40 and 50%, respectively, and three patients died from pulmonary hemorrhage. Invasive S.maltophilia infections are an emerging cause of infectious morbidity in patients receiving care at departments of pediatric hematology and oncology and carry a high case fatality rate. [ABSTRACT FROM AUTHOR]

Chromosomal instability (CIN) is a hallmark of cancer1. Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably 'silent' genomes with minimal CIN2. Here, we show in the EwS model how uncoupling of mitosis and cytokinesis via targeting protein regulator of cytokinesis 1 (PRC1) or its activating polo-like kinase 1 (PLK1) can be employed to induce fatal genomic instability and tumor regression. We find that the EwS-specific oncogenic transcription factor EWSR1-FLI1 hijacks PRC1, which physiologically safeguards controlled cell division, through binding to a proximal enhancer-like GGAA-microsatellite, thereby promoting tumor growth and poor clinical outcome. Via integration of transcriptome-profiling and functional in vitro and in vivo experiments including CRISPR-mediated enhancer editing, we discover that high PRC1 expression creates a therapeutic vulnerability toward PLK1 inhibition that can repress even chemo-resistant EwS cells by triggering mitotic catastrophe. Collectively, our results exemplify how aberrant PRC1 activation by a dominant oncogene can confer malignancy but provide opportunities for targeted therapy, and identify PRC1 expression as an important determinant to predict the efficacy of PLK1 inhibitors being used in clinical trials. In this study, the authors show that that oncogenic hijacking of PRC1 sensitizes genomically stable Ewing sarcoma cells for PLK1 inhibition alone or in synergy with a microtubule-destabilizing drug via induction of cytokinesis defects, rendering PRC1 a promising, broadly applicable predictive biomarker [ABSTRACT FROM AUTHOR]

The neurophysiology of the subjective sensation of being conscious is elusive; therefore, it remains controversial how consciousness can be recognized in patients who are not responsive but seemingly awake. During general anesthesia, a model for the transition between consciousness and unconsciousness, specific covariance matrices between the activity of brain regions that we call patterns of global brain communication reliably disappear when people lose consciousness. This functional magnetic imaging study investigates how patterns of global brain communication relate to consciousness and unconsciousness in a heterogeneous sample during general anesthesia and after brain injury. First, we describe specific patterns of global brain communication during wakefulness that disappear during propofol (n = 11) and sevoflurane (n = 14) general anesthesia. Second, we search for these patterns in a cohort of unresponsive wakeful patients (n = 18) and unmatched healthy controls (n = 20) in order to evaluate their potential use in clinical practice. We found that patterns of global brain communication characterized by high covariance in sensory and motor areas or low overall covariance and their dynamic change were strictly associated with intact consciousness in this cohort. In addition, we show that the occurrence of these two patterns is significantly related to activity within the frontoparietal network of the brain, a network known to play a crucial role in conscious perception. We propose that this approach potentially recognizes consciousness in the clinical routine setting. [ABSTRACT FROM AUTHOR]

Dose-response assays revealed that EwS cells were very sensitive towards triapine compared to osteosarcoma cells and non-transformed EwS patient-derived mesenchymal stem cells (mean IC SB 50 sb values 0.35, 1.63, 101.63 µM, respectively) (Fig. Keywords: Ewing sarcoma; RRM2; Targeted therapy; Prognostic biomarker; Paediatric oncology; Triapine; Chemoresistance EN Ewing sarcoma RRM2 Targeted therapy Prognostic biomarker Paediatric oncology Triapine Chemoresistance 1 7 7 07/30/21 20210727 NES 210727 Supplementary Information The online version contains supplementary material available at https://doi.org/10.1186/s12943-021-01393-9. To gain first insights into the biological function of I RRM2 i in EwS, we carried out gene ontology (GO) enrichment analysis of I RRM2 i co-expressed genes in 166 EwS tumours, which revealed that high I RRM2 i expression is closely correlated with cell proliferation-associated gene signatures (Fig. Pearson correlation coefficients between RRM2 and other genes were determined, of which those with |rPearson|> 0.5 were further analysed by GO enrichment analysis. f Kaplan-Meier survival analysis of 122 EwS patients stratified by RRM2 protein expression (low IRS <= 2, high IRS > 2). [Extracted from the article]

The dynamic interplay of integration and segregation in the brain is at the core of leading theoretical accounts of consciousness. The human brain dynamically alternates between a sub‐state where integration predominates, and a predominantly segregated sub‐state, with different roles in supporting cognition and behaviour. Here, we combine graph theory and dynamic functional connectivity to compare resting‐state functional MRI data from healthy volunteers before, during, and after loss of responsiveness induced with different concentrations of the inhalational anaesthetic, sevoflurane. We show that dynamic states characterised by high brain integration are especially vulnerable to general anaesthesia, exhibiting attenuated complexity and diminished small‐world character. Crucially, these effects are reversed upon recovery, demonstrating their association with consciousness. Higher doses of sevoflurane (3% vol and burst‐suppression) also compromise the temporal balance of integration and segregation in the human brain. Additionally, we demonstrate that reduced anticorrelations between the brain's default mode and executive control networks dynamically reconfigure depending on the brain's state of integration or segregation. Taken together, our results demonstrate that the integrated sub‐state of brain connectivity is especially vulnerable to anaesthesia, in terms of both its complexity and information capacity, whose breakdown represents a generalisable biomarker of loss of consciousness and its recovery. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Oscillations in the beta/low gamma range (10–45 Hz) are recorded in diverse neural structures. They have successfully been modeled as sparsely synchronized oscillations arising from reciprocal interactions between randomly connected excitatory (E) pyramidal cells and local interneurons (I). The synchronization of spatially distant oscillatory spiking E–I modules has been well-studied in the rate model framework but less so for modules of spiking neurons. Here, we first show that previously proposed modifications of rate models provide a quantitative description of spiking E–I modules of Exponential Integrate-and-Fire (EIF) neurons. This allows us to analyze the dynamical regimes of sparsely synchronized oscillatory E–I modules connected by long-range excitatory interactions, for two modules, as well as for a chain of such modules. For modules with a large number of neurons (> 105), we obtain results similar to previously obtained ones based on the classic deterministic Wilson-Cowan rate model, with the added bonus that the results quantitatively describe simulations of spiking EIF neurons. However, for modules with a moderate (~ 104) number of neurons, stochastic variations in the spike emission of neurons are important and need to be taken into account. On the one hand, they modify the oscillations in a way that tends to promote synchronization between different modules. On the other hand, independent fluctuations on different modules tend to disrupt synchronization. The correlations between distant oscillatory modules can be described by stochastic equations for the oscillator phases that have been intensely studied in other contexts. On shorter distances, we develop a description that also takes into account amplitude modes and that quantitatively accounts for our simulation data. Stochastic dephasing of neighboring modules produces transient phase gradients and the transient appearance of phase waves. We propose that these stochastically-induced phase waves provide an explanative framework for the observations of traveling waves in the cortex during beta oscillations. [ABSTRACT FROM AUTHOR]

Objective: As adolescent cancer patients may suffer from infertility following treatment, fertility counselling is essential. Our aim was to explore the current situation in four European countries in terms of (I) education about the risk for infertility, (II) counselling on fertility preservation, (III) patients' knowledge on fertility, (IV) sufficiency of information and (V) uptake of cryopreservation. Methods: In total, 113 patients (13–20 years) at 11 study centres completed a self‐report questionnaire three and six months after cancer diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI). Results: As many as 80.2% of participants reported having received education about the risk for infertility prior to treatment, 73.2% recalled counselling on fertility preservation. Only 52.3% stated they felt sufficiently informed to make a decision. Inability to recall counselling on fertility preservation (OR = 0.03, CI: 0.00–0.47) and female gender (OR = 0.11, CI: 0.03–0.48) was associated with lower use of cryopreservation, whereas older age was associated with higher use. Conclusion: Fertility counselling was available to a relatively high proportion of patients, and it did influence the utilisation of cryopreservation. However, many patients did not feel sufficiently informed. Further improvement is needed to enable adolescent cancer patients to make an informed decision on fertility preservation. [ABSTRACT FROM AUTHOR]

We analyzed Clostridioides difficile infection (CDI) rates and various antimicrobials' application densities from 2013 to 2019 at Leipzig University Hospital, Germany, by using multivariate linear regression. Ceftriaxone application was the only independent predictor of CDI incidence. Thus, antibiotics' specific pharmacokinetic and pharmacodynamic properties such as biliary excretion of ceftriaxone in its active form should be considered when determining their potential to cause CDI. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Local treatment of pelvic Ewing's sarcoma may be challenging, and intergroup studies have focused on improving systemic treatments rather than prospectively evaluating aspects of local tumor control. The Euro-EWING99 trial provided a substantial number of patients with localized pelvic tumors treated with the same chemotherapy protocol. Because local control included surgical resection, radiation therapy, or a combination of both, we wanted to investigate local control and survival with respect to the local modality in this study cohort.Questions/purposes: (1) Do patients with localized sacral tumors have a lower risk of local recurrence and higher survival compared with patients with localized tumors of the innominate bones? (2) Is the local treatment modality associated with local control and survival in patients with sacral and nonsacral tumors? (3) Which local tumor- and treatment-related factors, such as response to neoadjuvant chemotherapy, institution where the biopsy was performed, and surgical complications, are associated with local recurrence and patient survival in nonsacral tumors? (4) Which factors, such as persistent extraosseous tumor growth after chemotherapy or extent of bony resection, are independently associated with overall survival in patients with bone tumors undergoing surgical treatment?Methods: Between 1998 and 2009, 1411 patients with previously untreated, histologically confirmed Ewing's sarcoma were registered in the German Society for Pediatric Oncology and Hematology Ewing's sarcoma database and treated in the Euro-EWING99 trial. In all, 24% (339 of 1411) of these patients presented with a pelvic primary sarcoma, 47% (159 of 339) of which had macroscopic metastases at diagnosis and were excluded from this analysis. The data from the remaining 180 patients were reviewed retrospectively, based on follow-up data as of July 2016. The median (range) follow-up was 54 months (5 to 191) for all patients and 84 months (11 to 191) for surviving patients. The study endpoints were overall survival, local recurrence and event-free survival probability, which were calculated with the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) with their respective 95% CIs were estimated in a multivariate Cox regression model.Results: Sacral tumors were associated with a reduced probability of local recurrence (12% [95% CI 1 to 22] versus 28% [95% CI 20 to 36] at 5 years, p = 0.032), a higher event-free survival probability (66% [95% CI 51 to 81] versus 50% [95% CI 41 to 58] at 5 years, p = 0.026) and a higher overall survival probability (72% [95% CI 57 to 87] versus 56% [95% CI 47 to 64] at 5 years, p = 0.025) compared with nonsacral tumors. With the numbers available, we found no differences between patients with sacral tumors who underwent definitive radiotherapy and those who underwent combined surgery and radiotherapy in terms of local recurrence (17% [95% CI 0 to 34] versus 0% [95% CI 0 to 20] at 5 years, p = 0.125) and overall survival probability (73% [95% CI 52 to 94] versus 78% [95% CI 56 to 99] at 5 years, p = 0.764). In nonsacral tumors, combined local treatment was associated with a lower local recurrence probability (14% [95% CI 5 to 23] versus 33% [95% CI 19 to 47] at 5 years, p = 0.015) and a higher overall survival probability (72% [95% CI 61 to 83] versus 47% [95% CI 33 to 62] at 5 years, p = 0.024) compared with surgery alone. Even in a subgroup of patients with wide surgical margins and a good histologic response to induction treatment, the combined local treatment was associated with a higher overall survival probability (87% [95% CI 74 to 100] versus 51% [95% CI 33 to 69] at 5 years, p = 0.009), compared with surgery alone.A poor histologic response to induction chemotherapy in nonsacral tumors (39% [95% CI 19 to 59] versus 64% [95% CI 52 to 76] at 5 years, p = 0.014) and the development of surgical complications after tumor resection (35% [95% CI 11 to 59] versus 68% [95% CI 58 to 78] at 5 years, p = 0.004) were associated with a lower overall survival probability in nonsacral tumors, while a tumor biopsy performed at the same institution where the tumor resection was performed was associated with lower local recurrence probability (14% [95% CI 4 to 24] versus 32% [95% CI 16 to 48] at 5 years, p = 0.035), respectively.In patients with bone tumors who underwent surgical treatment, we found that after controlling for tumor localization in the pelvis, tumor volume, and surgical margin status, patients who did not undergo complete (defined as a Type I/II resection for iliac bone tumors, a Type II/III resection for pubic bone and ischium tumors and a Type I/II/III resection for tumors involving the acetabulum, according to the Enneking classification) removal of the affected bone (HR 5.04 [95% CI 2.07 to 12.24]; p < 0.001), patients with a poor histologic response to induction chemotherapy (HR 3.72 [95% CI 1.51 to 9.21]; p = 0.004), and patients who did not receive additional radiotherapy (HR 4.34 [95% CI 1.71 to 11.05]; p = 0.002) had a higher risk of death. The analysis suggested that the same might be the case in patients with a persistent extraosseous tumor extension after induction chemotherapy (HR 4.61 [95% CI 1.03 to 20.67]; p = 0.046), although the wide CIs pointing at a possible sparse-data bias precluded any definitive conclusions.Conclusion: Patients with sacral Ewing's sarcoma appear to have a lower probability for local recurrence and a higher overall survival probability compared with patients with tumors of the innominate bones. Our results seem to support a recent recommendation of the Scandinavian Sarcoma Group to locally treat most sacral Ewing's sarcomas with definitive radiotherapy. Combined surgical resection and radiotherapy appear to be associated with a higher overall survival probability in nonsacral tumors compared with surgery alone, even in patients with a wide resection and a good histologic response to neoadjuvant chemotherapy. Complete removal of the involved bone, as defined above, in patients with nonsacral tumors may be associated with a decreased likelihood of local recurrence and improved overall survival. Persistent extraosseous tumor growth after induction treatment in patients with nonsacral bone tumors undergoing surgical treatment might be an important indicator of poorer overall survival probability, but the possibility of sparse-data bias in our cohort means that this factor should first be validated in future studies.Level Of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

A foothold is a small position that a firm intentionally establishes within a market in which it does not yet compete. We extend theory on competitive dynamics to examine relationships between competitor analysis and foothold moves. Whereas it seems logical that an antecedent that is negatively related to the likelihood of foothold attack would be positively related to the likelihood of foothold withdrawal, we theorize and find evidence to the contrary. In a sample of firms with footholds, market commonality,resource similarity, and their interaction are each related in the same direction to both foothold attack and withdrawal. [ABSTRACT FROM AUTHOR]

We examine whether size-specific experience influences performance following large related, domestic acquisitions. Supporting a transfer theory of learning, our results suggest that although prior experience in making large, related acquisitions transfers positively to this focal situation, experience in making small related acquisitions hurts firm performance. We find that bidder-to-target dissimilarity in product offerings and geographic reach exacerbates the negative effects of experience in small related acquisitions. In contrast, perceived dissimilarity in organizational cultures curbs these negative effects. Moreover, retaining acquired top managers and engaging in less integration in large related acquisitions both aid acquirers in better drawing on experiences from smaller related acquisitions. [ABSTRACT FROM AUTHOR]