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Zusammenfassung Ziel der Studie Erhebung von Perspektiven palliativversorgender Hausärzte (HÄ)1 an der Schnittstelle zur SAPV und Verbesserungsvorschläge. Methodik Querschnittliche Befragung von HÄ aus acht Kassenärztlichen Vereinigungen (KV). Quantitative Analyse von 1144 Fragebögen zu Verbesserungsvorschlägen und qualitative Analyse von 187 Freitextkommentaren. Ergebnisse Eine bessere Qualifikation ambulanter Pflegedienste wurde am häufigsten (91,7 %) als wichtige Rahmenbedingung für die hausärztliche Palliativversorgung (PV) genannt. Die 187 Freitextkommentare adressierten vielschichtige Dimensionen hausärztlich erlebter PV: HÄ betonen ihre zentrale Rolle; die Beurteilung der SAPV-Einbindung variiert von Ressource bis zur hausärztlichen Ausgrenzung aus der Versorgung und Kompetenzabschreibung. Schlussfolgerung Geäußerte Lösungsansätze für empfundene Defizite sollten Gehör finden, wenn sie zu einer effizienten Deckung des PV-Bedarfs beitragen: bessere Qualifizierung der Pflegedienste; Vermeidung von Ausgrenzung von HÄ aus der Versorgung bei SAPV-Einbindung; bessere Vernetzung aller Akteure.

BackgroundMutation of thePRDM16gene has been associated with human cardiomyopathy. The PRDM16 protein is a transcriptional regulator affecting cardiac development via Tbx5 and Hand1 regulating myocardial structure. BiallelicPrdm16inactivation induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. Early pathological events uponPrdm16inactivation have not been explored.MethodsThis study performed in depth pathophysiological and molecular analysis of male and femalePrdm16csp1/wtmice carrying systemic, monoallelicPrdm16gene inactivation. We systematically assessed early molecular changes with transcriptomics, proteomics, and metabolomics. Kinetic modelling of the cardiac metabolism was undertakenin silicowith CARDIOKIN.ResultsPrdm16csp1/wtmice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice.Prdm16csp1/wthearts demonstrate moderate alterations of specific transcripts and protein levels with consistent upregulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre B-cell leukemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional upregulation was detected forPrdm16itself probably by an autoregulatory mechanism.Prdm16csp1/wtcardiac tissue showed reduction of metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and tricarboxylic acid cycle. Global lipid metabolism was also affected with accumulation of triacylglycerides detected in malePrdm16csp1/wthearts. In addition,Prdm16csp1/wtcardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. Metabolic modellingin silicosuggested lowered fatty acid utilization in male and reduced glucose utilization in femalePrdm16csp1/wtcardiac tissue.ConclusionsMonoallelicPrdm16mutation restricts cardiac performance inPrdm16csp1/wtmice. Metabolic alterations precede transcriptional dysregulation inPrdm16csp1/wtcardiac tissue. FemalePrdm16csp1/wtmice develop a more pronounced phenotype indicating a sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event inPRDM16associated cardiac pathology.Novelty and SignificanceWhat Is Known?- Mutation of thePRDM16gene has been associated with human cardiomyopathy.- Biallelic inactivation ofPrdm16in mice induces severe cardiac dysfunction with early postnatal lethality.- Prdm16 cooperates with transcription factors such as Tbx5 and Hand1 to activate transcriptional programs that define the development of the compacted myocardium.What New Information Does This Article Contribute?- Systemic, monoallelic inactivation inPrdm16csp1/wtmice induces cardiac dysfunction with normal survival.- Metabolic alterations are the leading pathophysiological consequences and induce cardiac hypoplasia. On the molecular level this is associated with upregulation of metabolic regulators Pyroxd2 and Pbxip1.- Metabolic response afterPrdm16inactivation occurs in a sex specific manner.

The COVID-19 pandemic represents a major public health threat. Risk of death from the infection is associated with age and pre-existing comorbidities such as diabetes, dementia, cancer, and impairment of immunological, hepatic or renal function. It remains incompletely understood why some patients survive the disease, while others do not. As such, we sought to identify novel prognostic factors for COVID-19 mortality. We performed an unbiased, observational retrospective analysis of real world data. Our multivariable and univariable analyses make use of U.S. electronic health records from 122,250 COVID-19 patients in the early stages of the pandemic. Here we show that a priori diagnoses of fluid, pH and electrolyte imbalance during the year preceding the infection are associated with an increased risk of death independently of age and prior renal comorbidities. We propose that future interventional studies should investigate whether the risk of death can be alleviated by diligent and personalized management of the fluid and electrolyte balance of at-risk individuals during and before COVID-19. Nahkuri et al. evaluate potential prognostic factors for COVID-19 mortality in a large US database of electronic health records. They find that fluid, pH and electrolyte imbalances – diagnosed at least one month prior to COVID-19 diagnosis – are associated with mortality. The clinical course of patients with COVID-19 is highly variable, with some patients barely affected and others dying. We wanted to better understand why this is the case and identify markers of COVID-19-associated mortality. To this end, we looked into the entire available medical history of more than 100,000 COVID-19 patients from the United States. We found that patients who had experienced a disturbance of electrolyte or fluid levels in the year before they contracted SARS-CoV-2 were more likely to die than patients without such a history. This observation suggests that careful monitoring and balancing of the hydration and electrolyte status during and even before a SARS-CoV-2 infection may be beneficial and possibly reduce the risk of death with COVID-19.

BACKGROUND: Sickle cell disease (SCD), an inherited red blood cell disorder, primarily affects African Americans in the United States. Adolescents and young adults with SCD (AYA-SCD) are at risk of high morbidity and mortality when transitioning from pediatric to adult care. The goal of this qualitative study was to understand factors associated with optimal implementation of the AYA-SCD transition. METHODS: Participants were recruited from a large hospital system and the community. Interview guides included topics on access to primary and specialized care, beliefs and practices related to pain control, transition from pediatric to adult care, and patient experiences in the emergency department (ED). Data were coded and analyzed using an inductive thematic coding approach in combination with a deductive coding approach using domains from the Consolidated Framework for Implementation Research (CFIR). RESULTS: Fifty-nine participants, including twenty-one AYA-SCD from both the pediatric and adult clinics, seventeen caregivers, nine pediatric SCD providers, six adult SCD providers, and six ED providers, completed 11 focus groups and 5 semi-structured interviews. Results identified multiple factors within the domains of CFIR including the outer setting, inner setting, individual characteristics, and intervention characteristics. Results were incorporated into a transition framework to inform local practice improvement. CONCLUSION: Our study highlights the importance of multi-level barriers and facilitators for AYA-SCD transition from pediatric to adult care. Future studies could use implementation science frameworks to understand local context and identify strategies and intervention characteristics to improve transition programming. These efforts will ultimately reduce health disparities and ensure health equity.

Objective: The objective was to evaluate the effect of a short physician training in smoking cessation on the physicians’ performance of smoking cessation interventions. The effects on patients’ cessation rates were analyzed as well. A further aim was to identify barriers for providing cessation interventions. The study was conducted in an acute care pulmonology department of a German university hospital. Methods: 24 physicians of the pulmonology department of a German university hospital received a two-hour training in smoking cessation. 109 pre- and 89 post-training group patients were compared with regard to the frequencies of received smoking cessation interventions (Ask, Advise, Assist) and three- and six-month abstinence rates. Physicians estimated their intervention frequencies and gave reasons for not providing cessation interventions. Results: In a multivariable analysis (p, Ziel: Das Ziel war die Evaluation der Effekte einer Ärzte-Kurzschulung zur Raucherentwöhnung auf die Anwendungshäufigkeit der Entwöhnungsstrategien durch die Ärzte. Ebenso wurden die Effekte auf die Abstinenzraten der Patienten untersucht. Außerdem sollten die Barrieren für die Durchführung von Raucherentwöhnungsmaßnahmen ermittelt werden. Die Studie wurde in einer pneumologischen Akutklinik eines deutschen Universitätsklinikums durchgeführt. Methoden: 24 Ärzte erhielten eine zweistündige Schulung zur Raucherentwöhnung. 109 Kontrollgruppenpatienten, die vor der Schulung in der Klinik behandelt wurden, wurden mit 89 nach der Schulung behandelten Studiengruppenpatienten hinsichtlich der Häufigkeit der ärztlichen Raucherentwöhnungsinterventionen (Ask, Advise, Assist) und ihrer Abstinenzraten drei und sechs Monate nach Klinikaufenthalt verglichen. Die Ärzte schätzten ihre Interventionshäufigkeiten und gaben Gründe an, warum sie in manchen Fällen keine Entwöhnungsinterventionen durchführten. Ergebnisse: Die Anwendung von „Ask“ (OR 3.28, 95% KI 1.13–9.53) durch die Ärzte und die Sechsmonats-Abstinenzraten (OR 2.70, 95% KI 1.24–5.84) waren in der Studiengruppe im multivariablen Modell signifikant höher (p, GMS German Medical Science; 18:Doc06

Material models are required to solve continuum mechanical problems. These models contain parameters that are usually determined by application-specific test setups. In general, the theoretically developed models and, thus, the parameters to be determined become increasingly complex, e.g., incorporating higher-order motion derivatives, such as the strain or strain rate. Therefore, the strain rate behaviour needs to be extracted from experimental data. Using image data, the most-common way in solid experimental mechanics to do so is digital image correlation. Alternatively, optical flow methods, which allow an adaption to the underlying motion estimation problem, can be applied. In order to robustly estimate the strain rate fields, an optical flow approach implementing higher-order spatial and trajectorial regularisation is proposed. Compared to using a purely spatial variational approach of higher order, the proposed approach is capable of calculating more accurate displacement and strain rate fields. The procedure is finally demonstrated on experimental data of a shear cutting experiment, which exhibited complex deformation patterns under difficult optical conditions.

National identity definitions determine who belongs to the national ingroup (e.g., “us Germans”) versus the “foreign” outgroup prone to hostile outgroup bias. We conducted five studies in two countries investigating if viewing the ingroup's national identity as fixed exacerbates the perceived divide between ingroup and outgroup and thus increases anti‐immigrant hostility, while a malleable view blurs the divide and reduces anti‐immigrant hostility. In a Prestudy (58 participants), an Implicit Theory of National Identity Scale was developed. In Studies 1 (154 participants) and 2 (390 participants), our scale predicted individuals’ prejudice and participation rates in a hypothetical referendum and a real petition against immigrants. In Studies 3 (225 participants) and 4 (225 participants), experimental evidence was obtained. Leading participants to believe that the definition of “a true compatriot” changes over time (rather than remaining the same) resulted in lower levels of prejudice and participation rates in an anti‐immigrant petition.

Using manual derivatization in gas chromatography-mass spectrometry samples have varying equilibration times before analysis which increases technical variability and limits the number of potential samples analyzed. By contrast, automated derivatization methods can derivatize and inject each sample in an identical manner. We present a fully automated (on-line) derivatization method used for targeted analysis of different matrices. We describe method optimization and compare results from using off-line and on-line derivatization protocols, including the robustness and reproducibility of the methods. Our final parameters for the derivatization process were 20 µL of methoxyamine (MeOx) in pyridine for 60 min at 30 °C followed by 80 µL N-Methyl-N-trimethylsilyltrifluoracetamide (MSTFA) for 30 min at 30 °C combined with 4 h of equilibration time. The repeatability test in plasma and liver revealed a median relative standard deviation (RSD) of 16% and 10%, respectively. Serum samples showed a consistent intra-batch median RSD of 20% with an inter-batch variability of 27% across three batches. The direct comparison of on-line versus off-line demonstrated that on-line was fit for purpose and improves repeatability with a measured median RSD of 11% compared to 17% using the same method off-line. In summary, we recommend that optimized on-line methods may improve results for metabolomics and should be used where available.

Background: Non-invasive ventilation (NIV) has been shown to be the most appropriate therapy for COPD patients with chronic respiratory failure. While physiological parameters and long-term outcome frequently serve as primary outcomes, very few studies have primarily addressed the impact of NIV initiation on sleep quality in COPD. Methods: This single-center prospective cohort study comprised NIV-naïve patients with COPD. All patients underwent polysomnographic evaluation both at baseline and at 3 months follow-up, accompanied by the assessment of health-related quality of life (HRQL) using the Severe Respiratory Insufficiency Questionnaire (SRI) and the Epworth Sleepiness Scale (ESS). A subgroup evaluation was performed to address the impact of comorbid obstructive sleep apnea syndrome (OSAS). Results: Forty-six patients were enrolled and twenty-five patients completed the follow-up period (66.7 ± 7.4 years). NIV resulted in an increase in slow-wave sleep (+2% (−3.5/7.5), p = 0.465) and rapid eye movement sleep (+2.2% (−1.0/5.4), p = 0.174), although no statistical significance could be detected. ESS (−1.7(−3.6/0.1), p = 0.066) also showed a positive trend. Significant improvements in the Respiratory Disturbance Index (RDI) (−12.6(−23.7/−1.5), p = 0.027), lung function parameters, transcutaneous PCO2 and the SRI summary scale (4.5(0.9/8), p = 0.016) were observed. Conclusion: NIV therapy does not decrease sleep quality and is even capable of improving HRQL, transcutaneous PaCO2, daytime sleepiness and RDI, and the latter especially holds true for patients with comorbid OSAS.

Increasingly complex numerical analyses require more and more precise, accurate and varied input parameters in order to achieve results that are as realistic and reliable as possible. Therefore, experimental analyses for material parameter identification are of high importance and a driving force for further developments. In this work, opportunities by applying fractal analysis to optical measurement data of a shear cutting process are investigated. The fractal analysis is based on a modification of the concept of scale-space filtering. Scale exponent fields are calculated for the image sequences of the shear cutting process that are taken by a mobile microscope. A least-square approximation is used for the automated evaluation of the local scale exponent values. In order to determine the change of the scale exponent of individual material points, a digital image correlation is applied.

Since 2007, patients receiving palliative care have been entitled to specialised outpatient palliative care (SAPV). Until now, the quality of care of the SAPV was only regionally focussed or in relation to individual SAPV teams. A nationwide analysis of outcome quality is still awaited. The organisation and design of structures and processes vary greatly from region to region, which complicates a comparative assessment of implementation. One way to measure the quality of the heterogeneous structures and processes is to collect patient-reported outcomes. Here, it is possible to use symptom burden, quality of care and patient satisfaction with SAPV care, since patients' quality of life is a central focus of SAPV care. This article is part of the research project SAVOIR, which is funded by the G-BA Innovation Fund.For this prospective longitudinal survey of the outcome quality of SAPV, structured data were collected at two measurement points (t42 SAPV teams agreed to participate in the study. They recruited a total of 964 patients at measurement time tThe SAPV patients recruited from a total of nine KV regions reported a reduced symptom burden and a high level of satisfaction with SAPV and rated the quality of care provided by SAPV as high.

Introduction: Prognostic scores are important tools in oncology to facilitate clinical decision-making based on patient characteristics. To date, classic survival analysis using Cox proportional hazards regression has been employed in the development of these prognostic scores. With the advance of analytical models, this study aimed to determine if more complex machine-learning algorithms could outperform classical survival analysis methods.Methods: In this benchmarking study, two datasets were used to develop and compare different prognostic models for overall survival in pan-cancer populations: a nationwide EHR-derived de-identified database for training and in-sample testing and the OAK (phase III clinical trial) dataset for out-of-sample testing. A real-world database comprised 136K first-line treated cancer patients across multiple cancer types and was split into a 90% training and 10% testing dataset, respectively. The OAK dataset comprised 1,187 patients diagnosed with non-small cell lung cancer. To assess the effect of the covariate number on prognostic performance, we formed three feature sets with 27, 44 and 88 covariates. In terms of methods, we benchmarked ROPRO, a prognostic score based on the Cox model, against eight complex machine-learning models: regularized Cox, Random Survival Forests (RSF), Gradient Boosting (GB), DeepSurv (DS), Autoencoder (AE) and Super Learner (SL). The C-index was used as the performance metric to compare different models.Results: For in-sample testing on the real-world database the resulting C-index [95% CI] values for RSF 0.720 [0.716, 0.725], GB 0.722 [0.718, 0.727], DS 0.721 [0.717, 0.726] and lastly, SL 0.723 [0.718, 0.728] showed significantly better performance as compared to ROPRO 0.701 [0.696, 0.706]. Similar results were derived across all feature sets. However, for the out-of-sample validation on OAK, the stronger performance of the more complex models was not apparent anymore. Consistently, the increase in the number of prognostic covariates did not lead to an increase in model performance.Discussion: The stronger performance of the more complex models did not generalize when applied to an out-of-sample dataset. We hypothesize that future research may benefit by adding multimodal data to exploit advantages of more complex models.

Classic galactosemia (OMIM #230400) is an autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the galactose-1-phosphate uridylyltransferase gene (GALT; 606999) on chromosome 9p13. Its diagnosis is established by detecting elevated erythrocyte galactose-1-phosphate concentration, reduced erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity. Biallelic pathogenic variants in the GALT gene is confirmed by DNA analysis. Our paper presents molecular characteristics of 195 Polish patients diagnosed with galactosemia I, intending to expand the current knowledge of this rare disease's molecular etiology. To the best of our knowledge, the described cohort of galactosemia patients is the largest single-center cohort presented so far. Supplementary Information The online version contains supplementary material available at 10.1186/s13023-021-01869-3.

The threat of COVID-19 has harried the world since early 2020. Risk of death from the infection is associated with age and pre-existing comorbidities such as diabetes, dementia, cancer, and impairment of immunological, hepatic or renal function. It still remains incompletely understood why some patients survive the disease, while others perish. Our univariate and multivariate analyses of real world data from U.S. electronic health records indicate that a priori diagnoses of fluid, pH and electrolyte imbalance are highly and independently associated with COVID-19 mortality. We propose that pre-existing homeostatic aberrations are magnified upon the loss of ACE2, which is a core component of the electrolyte management system as well as the entry point of internalizing SARS-CoV-2 viruses. Moreover, we also suggest such fragility of electrolyte homeostasis may increase the risk of plasma volume disturbances during the infection. Future interventional studies should investigate whether the risk of death can be alleviated by personalized management of the fluid and electrolyte balance of at-risk individuals before and during COVID-19.

BACKGROUND Due to the non-randomized nature of real-world data, prognostic factors need to be balanced, which is often done by propensity scores (PSs). This study aimed to investigate whether autoencoders, which are unsupervised deep learning architectures, might be leveraged to compute PS. METHODS We selected patient-level data of 128,368 first-line treated cancer patients from the Flatiron Health EHR-derived de-identified database. We trained an autoencoder architecture to learn a lower-dimensional patient representation, which we used to compute PS. To compare the performance of an autoencoder-based PS with established methods, we performed a simulation study. We assessed the balancing and adjustment performance using standardized mean differences, root mean square errors (RMSE), percent bias, and confidence interval coverage. To illustrate the application of the autoencoder-based PS, we emulated the PRONOUNCE trial by applying the trial's protocol elements within an observational database setting, comparing two chemotherapy regimens. RESULTS All methods but the manual variable selection approach led to well-balanced cohorts with average standardized mean differences

BackgroundDevelopment is rapid in the first years of life. Developmental delays appearing during this critical period have the potential to persist throughout the child’s life. Available standardized assessments for this age record a child’s ability to successfully complete discrete skills but fail to capture whether the child incorporates those skills into daily routines that are meaningful to the child and family. The Infant Toddler Activity Card Sort (ITACS) is a newly developed photograph-based early intervention tool to measure the participation-related concept of activity competence using caregiver report. The purpose of the present study was to use Rasch analysis to determine if ITACS items comprehensively measure the construct of child activity competence.ResultsA total of 60 child/caregiver dyads participated. The dichotomous caregiver-reported responses (present vs. absent) on the 40 individual ITACS items were used in Rasch analysis, and three iterations of the model were completed. The final model included 51 child/caregiver dyads and 67 ITACS assessments with a good spread of individual ability measure (6.47 logits). All items demonstrated adequate infit except for “sleeping” (range 0.68–1.54). Five items (sleeping, eating at restaurants, brushing teeth, crawling, and interact with pets) demonstrated high Mean Square (MNSQ) outfit statistics and one (take a bath) demonstrated low MNSQ outfit. ITACS items demonstrated a good spread of item difficulty measures (6.27 logits), and a clear ceiling was observed. Three activity items (smiling, breastfeeding, and playing with adults) were rarely endorsed as concerns. The activities most likely to be reported as challenging were “crying/communicating” and “going to school”. Person and item reliability statistics were adequate (0.79 and 0.80, respectively). The separation between individuals and between items were adequate to good (1.96 and 1.99, respectively).ConclusionsFindings indicate that ITACS items are measuring a unidimensional construct--activity competence in early childhood. The Rasch analysis of caregiver responses suggest that some activities are more likely to be considered challenging and may be important targets for intervention. These results provide evidence to further validate the ITACS as a caregiver report measure and support its use in the early intervention setting to facilitate caregiver driven goal development.

Abstract. The social integration of the ever-growing number of refugees in receiving societies is of major importance. Perceived discrimination has been found to predict fewer friendships with natives over time. But what short-term mechanisms explain this effect? In a sample of 115 refugees living in Germany we (i) replicated the long-term discrimination-social-integration relationship, (ii) found short-term associations between discrimination and affective, motivational, and behavioral tendencies not to befriend natives, and (iii) showed authenticity to mediate this short-term relationship: with increasing discrimination, refugees felt less like they could show their authentic selves around natives, which in turn impaired tendencies to befriend natives. Discrimination may impede the formation of interethnic friendships by instilling feelings of inauthenticity. Implications for prevention measures are discussed.

A new mass spectrometric method for evaluating metabolite formation of the pesticides thiacloprid, azoxystrobin, and difenoconazole was developed for the Brassica species pak choi and broccoli. Both, distribution and transformation kinetics of the active compounds and their metabolites were analyzed by UPLC-TWIMS-QTOF-MS. Additionally, HR-MS analysis and structure elucidation tools such as diagnostic ions, isotopic matches, and collision cross sections were applied for metabolites identification. Following the application of two plant protection products (containing the above-mentioned active compounds) in a greenhouse study plant material was cryo-milled and extracted with water/methanol. The residual levels of active compounds were identified at certain timepoints during pre-harvest intervals and in the final products. Different phase I and phase II metabolites of the pesticides were identified in different plant organs such as leaves, stems, (broccoli) heads, and roots. Three individual degradation pathways and distribution profiles are suggested including eight thiacloprid, eleven azoxystrobin and three difenoconazole metabolites.

A new sensitive, fast, and robust analytical method based on a QuPPe (Quick Polar Pesticides) extraction procedure coupled to ion chromatography-tandem mass spectrometry (IC-MS/MS) was developed. The study aimed at the determination of the highly polar pesticides chlorate, perchlorate, ethephon, and 2-hydroxyethylphosphonic acid (HEPA) in different plant food commodities. For achieving an acceptable dynamic range for chlorate and perchlorate and to compensate for matrix effects, the isotopically-labelled internal standards 18O3-chlorate and 18O4-perchlorate and ethephon D4 were applied for calibration. The optimized method was fully validated at levels of 0.010 and 0.100 mg kg−1 for all compounds in the matrices tomato, apple, lemon, sultana, avocado, and wheat according to the actual EU guidance document SANTE/11945/2015. For HEPA and the commodity sultana levels for validation were chosen at 0.050 mg kg−1 and 0.100 mg kg−1. The precision and accuracy of the validation results were determined at hand of five replicates with recovery rates between 93 and 119% and RSDs between 1 and 14%. The use of internal standards for chlorate, perchlorate and ethephon allows the determination in a wide working range between 0.01 and 1 mg kg−1 without interference by matrix effects. The developed analytical methodology is able to meet the strict requirements for the analysis of baby food.

An optimized method for the determination of residues of the plant growth regulators chlormequat, mepiquat, paraquat, and diquat in plant-derived commodities using LC-MS/MS was developed. As an exemplary, but very challenging commodity, the focus was set on the oil seed chia and the coverage of incurred residues of these quaternary ammonium compounds. The study describes the evaluation of optimum extraction conditions, particularly of the extraction solvent and a potential thermal treatment. The final procedure was accomplished by the extraction solvent methanol/hydrochloric acid at room temperature without the application of an extra heating step. The LC-MS/MS measurement was performed on an Obelisc R column (SIELC) within 16 min of separation time. For compensating matrix effects and differences in recovery rates, the isotopically labeled internal standards (ILIS) diquat d4, paraquat d6, mepiquat d3, and chlormequat d4 were added to the samples prior to the extraction. The validation of the method for the matrices tomato, lemon, sultana, wheat, and chia seed was carried out according to the actual guidance document SANTE/11945/2015 by the European Commission. The precision and accuracy were determined in five replicates at residual levels of 0.010 and 0.100 mg/kg obtaining recovery rates between 77 and 120% and RSDs between 1 and 13%. By means of the analytical method developed, it is possible to meet the strict requirements for the analysis of organic and baby food.

A multi-pesticide metabolite screening method using liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-Tof-MS) was developed for the detection of pesticide metabolites in fruit and vegetable samples. Based on a retrospectively created accurate mass compound database, a suspect screening approach was established for pesticides of high concern applied to a wide scope of plant-derived commodities. For each matrix, an individual scope of characteristic pesticides was selected and a scientific library of corresponding metabolites generated. The metabolite database contained a total of 648 pesticide metabolites originating from 58 active compounds. In 500 samples from daily routine analysis, 96 samples with positive detects for a total of 26 pesticides were re-analyzed for the occurrence of corresponding metabolites. Forty-seven different phase-I and phase-II metabolites were identified, respectively. The developed metabolite database can be applied for a suspect screening approach for pesticide metabolites identification in all kinds of fruits and vegetables. By the means of the results of the suspect screening workflow, a targeted screening method by UHPLC-MS/MS was established for individual pesticide metabolites. Positive detects for metabolites may give an unequivocal evidence for an illegal application of plant protection products, even if the active compound is not detectable anymore.

Background: The tumor microenvironment is an important factor in cancer immunotherapy response. To further understand how a tumor affects the local immune system, we analyzed immune gene expression differences between matching normal and tumor tissue. Methods: We analyzed public and new gene expression data from solid cancers and isolated immune cell populations. We also determined the correlation between CD8, FoxP3 IHC, and our gene signatures. Results: We observed that regulatory T cells (Tregs) were one of the main drivers of immune gene expression differences between normal and tumor tissue. A tumor-specific CD8 signature was slightly lower in tumor tissue compared with normal of most (12 of 16) cancers, whereas a Treg signature was higher in tumor tissue of all cancers except liver. Clustering by Treg signature found two groups in colorectal cancer datasets. The high Treg cluster had more samples that were consensus molecular subtype 1/4, right-sided, and microsatellite-instable, compared with the low Treg cluster. Finally, we found that the correlation between signature and IHC was low in our small dataset, but samples in the high Treg cluster had significantly more CD8+ and FoxP3+ cells compared with the low Treg cluster. Conclusions: Treg gene expression is highly indicative of the overall tumor immune environment. Impact: In comparison with the consensus molecular subtype and microsatellite status, the Treg signature identifies more colorectal tumors with high immune activation that may benefit from cancer immunotherapy. Cancer Epidemiol Biomarkers Prev; 27(1); 103–12. ©2017 AACR.

Date Presented 04/9/21 Development in the first years of life is often characterized by a child’s aptitude to complete discrete tasks, such as walking or stacking blocks. True participation requires the child to incorporate skills into everyday activities. This presentation will provide an overview of the Infant Toddler Activity Card Sort, the initial psychometrics, and a Rasch analysis. Primary Author and Speaker: Catherine R. Hoyt Contributing Authors: Ching-Fan Sheu

Background Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery. Methods We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care (n = 15) or CytoSorb® HA (n = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors’ activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII). Results Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors’ adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes. Conclusions CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts. Trial registration ClinicalTrials.gov NCT02775123. Registered 17 May 2016. Electronic supplementary material The online version of this article (10.1186/s13054-019-2399-4) contains supplementary material, which is available to authorized users.

Heart failure (HF) is usually defined by the dominantly affected heart chamber; therefore, termed right or left HF (RHF or LHF). Pulmonologists understand RHF as a complex syndrome characterized by insufficient delivery of blood from the right ventricle associated with elevated systemic venous pressure at rest or exercise. Cardiologists specify LHF by its clinical functional class and the relation to a reduced (HFrEF), preserved (HFpEF) or mid-range ejection fraction (HFmrEF). Pediatric cardiologist, dealing also with patients with a failing single ventricle, define HF as a condition of insufficient systemic oxygen delivery (DO(2)). Certainly, pediatricians do not think of the right and left heart, or even a single ventricle as an isolated, independently acting entity. Because of the importance of cardiac interactions, the creation of a restrictive atrial communication aims at a palliative approach with the goal to diminish the congestive consequences of a dysfunctional ventricle; further to serve as a pop-off valve in order to prevent syncope and cardiovascular collapse. This review covers the background, the particular indications, the techniques and preliminary results achieved following the creation of a restrictive atrial septum defect (rASD) in different pathophysiological settings. Based on the institutional experience, percutaneous trans-catheter perforation of the atrial septum, followed by gradual balloon dilatation can be performed at any age and location worldwide. Medical institutions in low resource countries can make use of such palliating procedures in the setting of right as well as LHF independent of their pharmacological facilities.

Objective The goal of the present study was to investigate lines of therapy with biological drugs in patients followed in dermatology, gastroenterology, and rheumatology practices in Germany. Materials and methods The study included patients aged 18 years or over who had received a biological therapy in dermatology, gastroenterology, or rheumatology practices in Germany in 2017 (index date). The primary outcome of the study was the prevalence of different lines of therapy (first-, second-, third-, and at least fourth-line therapies) by type of practice, age, and gender. The second outcome was the association between basic characteristics (type of practice, age, and gender) and lines of therapy with biological drugs. Results The present study included 27,816 individuals. The mean age (SD) at index date was 50.7 years (15.4 years). Biological drugs were prescribed as first-line therapies in 60% of patients (dermatology 73%, gastroenterology 61%, and rheumatology 56%). The prevalence of first-line therapies ranged from 57% in individuals aged 41 - 50 years to 65% in those aged 18 - 30 years. Furthermore, 56% of women and 61% of men were prescribed biological drugs as first-line therapies. Finally, the likelihood of being prescribed biological drugs as second-, third-, or at least fourth-line therapies was significantly associated with being followed in a rheumatology or gastroenterology practice, older age, and female gender. Conclusion Biological drugs were prescribed as first-line therapies in most cases. The type of practice as well as the patient's age and gender had a significant impact on lines of therapy with biological drugs. .

BackgroundLeft atrial congestion results from backward failure in dilated cardiomyopathy. We aimed to evaluate feasibility and efficacy of percutaneous atrioseptostomy to create a restrictive atrial septum defect in management of dilated cardiomyopathy.Methods and resultsFrom June 2009 to December 2016, 27 interventions comprised left atria decompressions in 22 dilated cardiomyopathy patients; 9 females; age: 24 days to 36.9 years; weight: 3–50 kg; NYHA-/Ross class IV (n=16). Mean left ventricular ejection fraction was 21.5±9.7% and brain natriuretic peptide was 2291±1992 pg/ml. Dilated cardiomyopathy was classified as chronic (n=9); acute (n=1) myocarditis; idiopathic (n=5); left ventricular non-compaction (n=4); mitochondriopathy, pacemaker induced, and arrhythmogenic (n=3). Atrioseptostomy was concomitantly performed with myocardial biopsies 6.5 days (±11.7) after admission (n=11). Trans-septal puncture was used in 18 patients; foramen ovale dilatation was done in four patients. Mean balloon size was 11 mm (range 7–14 mm); total procedure time was 133±38 minutes. No procedural complications were observed. Mean left atrial pressure decreased from 15.8±6.8 to 12.2±4.8 mmHg (p=0.005), left/right atrial pressure gradient from 9.6±5.6 to 5±3.5 mmHg; brain natriuretic peptide (n=18) decreased from 1968±1606 to 830±1083 pg/ml (p=0.01). One patient unsuitable for heart transplantation died at home despite additionally performed pulmonary artery banding and three further left atrial decompressions; five patients were bridged to transplantation, two died afterwards. Functional recovery occurred in the remaining 14 patients and in six after additional pulmonary artery banding. No patient required assist device.ConclusionsPercutaneous left atrial decompression is an age-independent, effective palliation treating patients with dilated cardiomyopathy.