The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

How do parents perceive their children's epileptic seizures? Experiences of the first seizure and changes during the course of the epilepsy.

PROBLEM: Experiencing a child's seizure can be challenging for parents. METHODS: We investigated parental experiences of their child's first seizure and how their perception and management of seizures changed over time. From September 2020 to March 2021, we invited parents who had witnessed at least two of their child's seizures to take part in a semi-structured interview. Parents whose children experienced solely absence seizures were excluded. RESULTS: Of the parents, 52/74 (70%) did not recognize their child's first epileptic seizure and assumed the event to be due to a different cause, for instance teething. Parents overwhelmingly reported fear (48/74; 65%) and surprise (13/74; 18%) as the predominant emotional responses to the first seizure. In response to the most recently observed seizure parents reported feelings related to fear (33/74; 45%) and happiness (16/74; 22%), with regard to the latter, especially "being calm" or "feeling safe". Asked for thoughts in response to the first seizure, 22/74 (30%) reported concerns about their child's future, with regard to the most recent seizure, 15/74 (20%) expressed such thoughts. Of the parents, 53/74 (72%) did not know how to respond to the first seizure. Concerning the most recent seizure, 48/74 (65%) said they felt confident in managing the seizure. CONCLUSION: Experiencing the child's first seizure was very challenging for parents. During the course of the epilepsy, changes were observed in both parental perception of and confidence in managing the seizures. Physicians should consider these changes when counselling parents in order to better target their evolving needs.

Association between ideal cardiovascular health and depression incidence: a longitudinal analysis of ELSA-Brasil.

OBJECTIVE: We investigated whether ideal cardiovascular health (ICH), a metric proposed by the American Heart Association, predicts depression development. METHODS: Cohort analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Adults with no current depression and other common mental disorders, cardiovascular diseases, and antidepressant drug use at baseline had their ICH (composite score of smoking, dietary habits, body mass index, blood pressure, fasting glucose, cholesterol, and physical activity) assessed and classified into poor, intermediate, and optimal. Depression was assessed using the Clinical Interview Schedule-Revised (CIS-R). Poisson regression models, adjusted for sociodemographic factors and alcohol consumption, were employed. Stratified analyses were performed for age and sex. RESULTS: We included 9214 participants (mean age 52 ± 9 years, 48.6% women). Overall depression incidence at 3.8-year follow-up was 1.5%. Intermediate and poor ICH significantly increased the risk rate (RR) of developing depression (2.48 [95%CI 1.06-5.78] and 3 [1.28-7.03], respectively) at a 3.8-year follow-up. Higher ICH scores decreased the rate of depression development (RR = 0.84 [0.73-0.96] per metric). Stratified analyses were significant for women and adults < 55 years old. CONCLUSIONS: Poor cardiovascular health tripled depression risk at follow-up in otherwise healthy adults. Ameliorating cardiovascular health might decrease depression risk development.

Anti-Inflammatory Substances in Wheat Malt Inducing Antisecretory Factor.

Extensively malted cereals counteract enterotoxic diarrhea and inflammatory bowel diseases. This effect depends on a protein called antisecretory factor (AF), which is secreted into the blood as a larger complex known as the compleasome. In this study, we identified anti-inflammatory substances in malt and assayed their capacity to induce AF. Guaiacol and quercetin inhibited inflammation in a mouse footpad model, while catechin, sinapic acid, ferulic acid, and quercetin inhibited nitric oxide formation in RAW 264.7 cells. The proteasome activity in these cells was inhibited by vanillic acid and quercetin but not by the other tested phenols. As the transient receptor potential vanilloid 1 (TRPV1) might be involved in AF induction, the TRPV1 antagonist capsazepine was tested and shown to inhibit inflammation in mouse paw and nitric oxide formation. Catechin, ferulic acid, and sinapic acid induced AF in rat blood, and these substances were all increased in malt compared to control wheat. These phenols might therefore be of particular importance for the beneficial effect of malted cereals on inflammatory diseases. Our results further suggest that TRPV1 might play a role in the anti-inflammatory activity of phenols via the induction of AF.

Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.

AIM: To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to participate or not. MATERIALS AND METHODS: Between 2011 and 2015, 8,061 women (50-75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent. RESULTS: Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51-59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were "MRI-related inconveniences and/or self-reported contraindications to MRI" (27%) and "anxiety regarding the result of supplemental screening" (21%). "Expected personal health benefit" (68%) and "contribution to science" (43%) were the most frequent reasons for participation. CONCLUSION: Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were "MRI-related inconveniences" and "anxiety regarding the result of supplemental screening". In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.

In-hospital mortality after acute STEMI in patients undergoing primary PCI.

BACKGROUND: Acute myocardial infarction (AMI) is the main cause of global and in-hospital mortality in patients with cardiovascular diseases. We aimed to examine the association between the coronary artery involved and the in-hospital mortality in patients who underwent primary percutaneous coronary intervention (pPCI) after ST segment elevation myocardial infarction (STEMI). METHODS: The in-hospital mortality of STEMI patients who underwent pPCI was assessed at the Department of Cardiology, Harzklinik Goslar, Germany, which has no access to immediate mechanical circulatory support (MCS), between 2013 and 2017. RESULTS: We enrolled 312 STEMI patients, with a mean age of 67.1 ± 13.4 years, of whom 211 (68%) were male. In-hospital mortality was documented in 31 patients (10%). In-hospital mortality was associated with pre-hospital cardiopulmonary resuscitation (CPR; n = 39/12.5%), older age, lower systolic blood pressure, Killip class > 1, triple-vessel disease (each p < 0.0001), female gender (p = 0.0158), and with the localization of the treated culprit lesion in the left main coronary artery (LMCA; p = 0.0083) and in the ramus circumflexus (RCX; p = 0.0141). CONCLUSION: In this monocentric cohort, all-cause in-hospital mortality of STEMI patients after pPCI was significantly higher in those patients with culprit lesions in the LMCA and in the RCX, which may prove to be a substantial novel risk factor for STEMI-related mortality. Increasing age and female gender may be interdependent risk factors for mortality in this patient population. Furthermore, our data highlight the importance of the availability of MCS options in pPCI centers for patients after CPR.

Exercise-induced alterations and loss of sarcomeric M-line organization in the diaphragm muscle of obscurin knockout mice.

We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution of ankyrin B (ankB), disorganization of the subsarcolemmal microtubules, and reduced localization of dystrophin at costameres. In addition, these mice have impaired running endurance and increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach of physiological, morphological, and structural studies in which we further characterize the skeletal muscles of obscurin KO mice. A detailed examination of exercise performance, using different running protocols, revealed that the reduced endurance of obscurin KO animals on the treadmill depends on exercise intensity and age. Indeed, a mild running protocol did not evidence significant differences between control and obscurin KO mice, whereas comparison of running abilities of 2-, 6-, and 11-mo-old mice exercised at exhaustion revealed a progressive age-dependent reduction of the exercise tolerance in KO mice. Histological analysis indicated that heavy exercise induced leukocyte infiltration, fibrotic connective tissue deposition, and hypercontractures in the diaphragm of KO mice. On the same line, electron microscopy revealed that, in the diaphragm of exercised obscurin KO mice, but not in the hindlimb muscles, both M-line and H-zone of sarcomeres appeared wavy and less defined. Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.

Improved clinical trial enrollments for uterine leiomyosarcoma patients after gynecologic oncology partnership with a sarcoma center.

OBJECTIVE: A retrospective chart review was performed to determine patient outcomes before and after partnership by gynecologic oncologists (GYN/ONC) with a sarcoma center (SC) for patients with recurrent unresectable/metastatic (RM) uterine leiomyosarcoma (uLMS). METHODS: 58 RM patients, identified from medical records of uLMS patients cared for by either GYN/ONC service and/or the SC between 1/1/2000-4/1/2014, were audited for patient and tumor characteristics, outcomes, and clinical trials enrollments. RESULTS: Of the 58 patients, 26 patients (48%) were treated by GYN/ONC alone and 32 were treated by a combination of GYN/ONC and SC (52%). Age, race, tumor size, grade, presence of lymphovascular invasion, cervical involvement, and FIGO stage at diagnosis were not statistically different between the two groups. There was a significant difference between the number of clinical trial enrollments (0.07 vs 0.84 trials/patient, p<0.001) and the number of chemotherapy regimens prescribed (2.67 vs 4.29/patient, p=0.03) by GYN/ONC vs SC; the latter was driven by the number of clinical trial enrollments by the SC. Sixty-nine percent of patients referred to the SC were enrolled in at least one clinical trial, while just 8% of patients in the GYN/ONC group were enrolled in at least one clinical trial, a difference that is significant (p<0.0001). CONCLUSIONS: Referral of RM uLMS patients by GYN/ONC to a dedicated clinical trials-based SC resulted in an increase in the number of chemotherapy regimens prescribed and clinical trial enrollments. Partnership between GYN/ONC and a dedicated SC with access to clinical trials should be encouraged for all RM uLMS patients.

Alcohol use and self-perceived mental health status among pregnant and breastfeeding women in Canada: a secondary data analysis.

OBJECTIVE: To estimate the prevalence of alcohol consumption during pregnancy and while breastfeeding in Canada from 2003 to 2010, and to test the relation between self-perceived mental health status and alcohol consumption during pregnancy and while breastfeeding. DESIGN: Secondary analysis of four cycles of the Canadian Community Health Survey, a population-based cross-sectional survey. SETTING: Canada. SAMPLE: A total of 18 612 pregnant and 15 836 breastfeeding women. METHODS: The prevalence of alcohol consumption during pregnancy and while breastfeeding and 95% confidence intervals (CI) were calculated by province and territory, and cycle. The relation between self-perceived mental health status and alcohol consumption during pregnancy and while breastfeeding was explored using quasi-Poisson regression models. MAIN OUTCOME MEASURES: Alcohol consumption during pregnancy and while breastfeeding, and self-perceived mental health status. RESULTS: In Canada, between 2003 and 2010, approximately one in every ten pregnant women (9.9%; 95%CI 9.2-10.5%) and two in every ten breastfeeding women (20.3%; 95%CI 19.4-21.2%) women consumed alcohol. Women with a lower self-perceived mental health status (i.e. 'good') were 1.40 (95%CI 1.18-1.67, P < 0.001) times more likely to have consumed alcohol during pregnancy, compared with women with an 'excellent' self-perceived mental health. There were no notable differences between the categories of mental health status in regard to alcohol consumption while breastfeeding. CONCLUSION: Despite public health efforts in Canada, a significant proportion of pregnant and breastfeeding women consume alcohol. It is imperative that a standard screening protocol be initiated among pregnant and breastfeeding women, especially in high-risk populations (e.g. women utilising substance abuse treatment programs). TWEETABLE ABSTRACT: In Canada in 2003-2010, approximately 10% of pregnant and 20% of breastfeeding women consumed alcohol.

[Antibiotic Consumption and the Development of Antibiotic Resistance in Surgical Units]. / Antibiotikaverbrauch und Resistenzentwicklung in der Chirurgie.

BACKGROUND: Antibiotic resistence is increasing worldwide. AIM: A longitudinal analysis of the influence of the density of antibiotic use on the development of resistance in surgical units was undertaken. MATERIAL AND METHODS: Over five years the incidence of pathogens and the resistance rates of isolates from patients of normal surgical units and those of a surgical ICU at a university hospital were examined. The resistence rates were correlated with the density of antibiotic use - calculated from the antibiotic consumption (in DDD) and the number of patient-days. RESULTS: At both units, Enterobacteriaceae and Enterococci were mostly cultured. Among the Enterobacteriaceae, E. coli, Klebsiella spp., Proteus mirabilis and Enterobacter predominated. In the group of Enterococci, E. faecalis predominated at wards whereas at ICU E. faecium was the most frequent. Anaerobes ranked third at normal wards and Candida spp. at ICU. From 2007 to 2011, there was an increasing resistance against ciprofloxacin in P. mirabilis (r = 0.87; p = 0.054) and against imipenem (r = 0.86; p = 0.06) and piperacillin (r = 0.81; p = 0.09) in P. aeruginosa at normal wards. At ICU, the resistance rates of imipenem in P. aeruginosa rose (r = 0.88; p = 0.049). Resistance against ciprofloxacin in E. coli increased (r = 0.65; p = 0.23). Due to the increasing use of ciprofloxacin and meropenem at normal wards, the density of antibiotic usage rose 1.4 %/year (r = 0.94; p = 0.02). Despite the increase of meropenem use at ICU (r = 0.9; p = 0.035), the total antibiotic uptake rate remained almost constant. The antibiotic usage density was 3-fold higher at ICU than at normal wards. At normal wards, the ciprofloxacin usage correlated with the rate of resistance against ciprofloxacin in P. mirabilis P. m. At ICU, an association was detected between the uptake rate of ceftazidime and the rate of resistance against cefotaxime in the CES group. In P. aeruginosa, the use of piperacillin and the rate of resistance against piperacillin correlated. CONCLUSION: The high uptake rates of fluoroquinolones and carbapenems were accompanied by increases in resistances. The resistance rates are influenced by hygiene management and microbiological diagnostics. The extensive use of carbapenems should be reassessed on both units to counter further development of antibiotic resistance.

Role of vesicular nucleotide transporter VNUT (SLC17A9) in release of ATP from AR42J cells and mouse pancreatic acinar cells.

ATP is released from cells in response to various stimuli. Our previous studies on pancreas indicated that pancreatic acini could be major stores of secreted ATP. In the present study, our aim was to establish the role of the vesicular nucleotide transporter (VNUT), SLC17A9, in storage and release of ATP. Freshly prepared acini from mice and AR42J rat acinar cells were used in this study. We illustrate that in AR42J cells, quinacrine (an ATP store marker) and Bodipy ATP (a fluorescent ATP analog) co-localized with VNUT-mCherry to vesicles/granules. Furthermore, in acini and AR42J cells, a marker of the zymogen granule membranes, Rab3D, and VNUT co-localized. Dexamethasone treatment of AR42J cells promoted formation of acinar structures, paralleled by increased amylase and VNUT expression, and increased ATP release in response to cholinergic stimulation. Mechanical stimulus (pressure) and cell swelling also induced ATP release, but this was not influenced by dexamethasone, most likely indicating different non-zymogen-related release mechanism. In conclusion, we propose that VNUT-dependent ATP release pathway is associated with agonist-induced secretion process and downstream purinergic signalling in pancreatic ducts.

Penetration studies of an extremely lipophilic active model substance from an oil-in-water emulsion: influence of the lipophilicity of the formulation in human skin - part 2.

The effect of the lipophilicity of a carrier on human skin penetration of an extremely lipophilic active model substance was evaluated by using Franz type diffusion cells. Oil-in-water model emulsions containing different amounts of the oily phase were prepared, and Myritol® PC (M-PC) was selected as lipophilic marker component of the oily phase. The penetrated amounts of the lipophilic model substance salicyloyl phytosphingosine (SP) were determined by high-performance liquid chromatography with ultraviolet detection, while M-PC was detected using gas chromatography coupled with mass spectrometry. It has been ascertained that the amount of the lipid phase within the emulsion influenced the penetration profile of the active ingredient SP. The emulsion containing the lowest proportion of the lipid phase provides the best conditions for SP penetration. Surprisingly, the penetration behavior of M-PC was influenced by the oily phase in the same way. Regarding the M-PC and the SP penetration profiles from each emulsion, a solvent drag mechanism can be assumed whereby M-PC acts as penetration enhancer. In conclusion, the penetration rate of the active ingredient SP and the marker component M-PC are in reverse proportion to the oil content of the formulations. The lipophilicity of SP and M-PC, their solubility and their thermodynamic activity within the vehicle could have an effect on their penetration behavior. Additionally, M-PC has the property to enhance the penetration rates of extremely lipophilic substances even at low concentrations.

Global structure of regular tori in a generic 4D symplectic map.

For the case of generic 4d symplectic maps with a mixed phase space, we investigate the global organization of regular tori. For this, we compute elliptic 1-tori of two coupled standard maps and display them in a 3d phase-space slice. This visualizes how all regular 2-tori are organized around a skeleton of elliptic 1-tori in the 4d phase space. The 1-tori occur in two types of one-parameter families: (α) Lyapunov families emanating from elliptic-elliptic periodic orbits, which are observed to exist even far away from them and beyond major resonance gaps, and (ß) families originating from rank-1 resonances. At resonance gaps of both types of families either (i) periodic orbits exist, similar to the Poincaré-Birkhoff theorem for 2d maps, or (ii) the family may form large bends. In combination, these results allow for describing the hierarchical structure of regular tori in the 4d phase space analogously to the islands-around-islands hierarchy in 2d maps.

[Postoperative long-term results in high-grade traumatic ruptures of the spleen in children]. / Postoperative Ergebnisse höhergradiger traumatischer Milzrupturen bei Kindern im Langzeitverlauf.

BACKGROUND: Splenic rupture is the most common injury in blunt abdominal trauma at any age. The grade of rupture, haemodynamic stability and, in the case of operative treatment, the experience of the surgeon all play an important role in preserving the spleen. Due to its important immunological function preservation of the spleen should be the goal. PATIENTS: From January 2000 to August 2009 five children (4 male/1 female) with isolated grade IV or V splenic rupture, according to the Organ Injury Score (OIS), were treated operatively. At the time of the trauma the patients were 8.8 ± 3.8 (mean ± standard deviation; range, 6­15) years old. Four patients with an OIS grade IV rupture were primarily treated with partially spleen-saving surgery: one resection of 2/3 of the spleen including the splenic vessels, one hemisplenectomy and two lower pole resections; in one patient with an OIS grade V rupture splenectomy was performed immediately. RESULTS: In one patient treated with a spleen-preserving approach (hemisplenectomy) the remainder of the spleen had to be removed due to acute bleeding on the first postoperative day. This patient needed two units of blood transfused following the second operation. There were no other complications. The two patients with splenectomy and resection of ⅔ of the spleen developed a transient thrombocytosis indicating impaired clearance of the spleen. In a follow-up involving ultrasonography (median 13, range 1-101 months) all patients managed with partially spleen-saving surgery showed a large remnant spleen with arterial perfusion. CONCLUSION: The majority of primarily partially spleen-preserving operations result from OIS grade IV ruptures of the spleen. Use of a partially spleen-saving surgical approach was successful in ¾ of these patients. Low morbidity and documented perfusion of the remnant spleen at long-term follow-up indicate that a spleen-preserving technique is warranted if an operative approach is required.

Expression and prognostic significance of hsa-miR-142-3p in acute leukemias.

OBJECTIVES: The microRNA 142 (miR-142) is expressed at high levels in mature hematopoietic cells and has a crucial role during T-lymphocyte development. Its role in leukemogenesis is unclear. PATIENTS AND METHODS: Expression of miR-142 was analyzed in acute myeloid and lymphoblastic leukemia cells (de novo, cell lines). Data were compared to expression in CD34+ hematopoietic cells. Based on the miR-142 expression, clinical data such as overall survival was analyzed. RESULTS: MiR-142 expression in all leukemia cell lines and 86 % of the de novo samples was higher than in CD34+ cells. This difference could be detected in both, myeloid and lymphoid neoplastic cells. In AML patients with intermediate cytogenetic risk a high miR-142 expression was associated with a better overall survival. CONCLUSIONS: MiR-142 expression in acute lymphoblastic as well as myeloid leukemia cells is higher than in CD34+ cells. Additionally, miR-142 expression might have prognostic relevance in AML-patients with otherwise an intermediate cytogenetic risk.

Latent pulmonary hypertension in atrial septal defect: Dynamic stress echocardiography reveals unapparent pulmonary hypertension and confirms rapid normalisation after ASD closure.

OBJECTIVE: Closure of atrial septal defects (ASD) prevents pulmonary hypertension, right heart failure and thromboembolic stroke. The exact timing for ASD closure is controversial. METHODS: In a prospective study to address the question whether unapparent pulmonary hypertension can be revealed prior to right ventricular (RV) remodelling, patients were investigated before and 6, 12, and 24 months after ASD closure using exercise stress echocardiography (ESE) and ergospirometry (n = 24). RESULTS: At rest, RV systolic pressure (RVSP) was normal in 58.8 %, slightly elevated in 26.5 %, and moderately elevated in 11.8 %. One patient showed severe pulmonary hypertension. During ESE, all patients with normal RVSP at rest exhibited an increase (25.7 ± 1.2 mmHg vs. 45.3 ± 2.3 mmHg, p < 0.001). After closure the RVSP was lower, both at rest and ESE. RV diameters decreased too. Tricuspid annulus plane systolic excursion (TAPSE) at rest remained lower after closure (24.0 ± 0.9 vs. 22.0 ± 0.9 mm, p < 0.05). TAPSE in ESE was elevated, and stayed stable after closure (30.1 ± 1.8 mm vs. 29.3 ± 1.6 mm). Before closure, RV systolic tissue velocities (s(a)) at rest were normal and decreased after closure (14.0 ± 1.0 cm/s vs. 11.5 ± 0.7 (6 month) vs. 10.6 ± 0.5 cm/s (12 month), p < 0.05). During ESE, s(a) velocity was similar before and after closure (23.0 ± 1.3 cm/s vs. 23.3 ± 1.9 cm/s). Maximal oxygen uptake (VO2/kg) did not differ between baseline and follow-ups. CONCLUSION: Latent pulmonary hypertension may become apparent in ESE. ASD closure leads to a significant reduction in this stress-induced pulmonary hypertension and to a decrease in the right heart diameters indicating reverse RV remodelling. RV functional parameters at rest did not improve. The VO2/kg did not change after ASD closure.

Air pollution accountability research: Moving from a chain to a web.

Air pollution accountability studies examine the relationship(s) between an intervention, regulation, or event and the resulting downstream impacts, if any, on emissions, exposure, and/or health. The sequence of events has been schematically described as an accountability chain. Here, we update the existing framework to capture real-life complexities and to highlight important factors that fall outside the linear chain. This new "accountability web" is intended to convey the intricacies associated with conducting an accountability study to various audiences, including researchers, policy makers, and stakeholders. We also identify data considerations for planning and completing a robust accountability study, including those relevant to novel and innovative air pollution and exposure data. Finally, we present a series of recommendations for the accountability research community that can serve as a guide for the next generation of accountability studies.

Early clinical trial unit tumor board: a real-world experience in a national cancer network.

PURPOSE: Early clinical trials are the first step into clinical therapies for new drugs. Within the six Bavarian university-based hospitals (Augsburg, Erlangen, Regensburg, Munich (LMU and TU), Würzburg) we have enrolled a virtual network platform for patient discussion. METHODS: The virtual Early Clinical Trial Unit Tumor Board (ECTU Tumor Board) is a secured web-based meeting to evaluate early clinical trial options for patients, where representatives from local ECTUs participate. We retrospectively analyzed patient cases discussed between November 2021 and November 2022. RESULTS: From November 2021 to November 2022, a total of 43 patients were discussed in the ECTU Tumor Board. Median age at diagnosis was 44.6 years (range 10-76 years). The median number of previous lines of therapies was 3.7 (range 1-9 therapies) including systemic treatment, surgery, and radiation therapy. A total of 27 different tumor entities were presented and 83.7% (36/43) patients received at least one trial recommendation. In total, 21 different active or shortly recruiting clinical trials were recommended: ten antibody trials, four BiTE (bispecific T cell engager) trials, six CAR (chimeric antigen receptor) T-cell trials, and one chemotherapy trial. Only six trials (28.6%) were recommended on the basis of the previously performed comprehensive genetic profiling (CGP). CONCLUSION: The ECTU Tumor Board is a feasible and successful network, highlighting the force of virtual patient discussions for improving patient care as well as trial recruitment in advanced diseases. It can provide further treatment options after local MTB presentation, aiming to close the gap to access clinical trials.

Influence of paced maternal breathing on fetal-maternal heart rate coordination.

Pregnant mothers often report a special awareness of and bonding with their unborn child. Little is known about this relationship although it may offer potential for the assessment of the fetal condition. Recently we found evidence of short epochs of fetal-maternal heart rate synchronization under uncontrolled conditions with spontaneous maternal breathing. Here, we examine whether the occurrence of such epochs can be influenced by maternal respiratory arrhythmia induced by paced breathing at several different rates (10, 12, 15, and 20 cycles per minute). To test for such weak and nonstationary synchronizations among the fetal-maternal subsystems, we apply a multivariate synchronization analysis technique and test statistics based on twin surrogates. We find a clear increase in synchronization epochs mostly at high maternal respiratory rates in the original but not in the surrogate data. On the other hand, fewer epochs are found at low respiratory rates both in original and surrogate data. The results suggest that the fetal cardiac system seems to possess the capability to adjust its rate of activation in response to external--i.e., maternal--stimulation. Hence, the pregnant mothers' special awareness to the unborn child may also be reflected by fetal-maternal interaction of cardiac activity. Our approach opens up the chance to examine this interaction between independent but closely linked physiological systems.