Optimizing the Analytical Value of Oncology-Related Data Based on an In-Memory Analysis Layer: Development and Assessment of the Munich Online Comprehensive Cancer Analysis Platform.

BACKGROUND: Many comprehensive cancer centers incorporate tumor documentation software supplying structured information from the associated centers' oncology patients for internal and external audit purposes. However, much of the documentation data included in these systems often remain unused and unknown by most of the clinicians at the sites. OBJECTIVE: To improve access to such data for analytical purposes, a prerollout of an analysis layer based on the business intelligence software QlikView was implemented. This software allows for the real-time analysis and inspection of oncology-related data. The system is meant to increase access to the data while simultaneously providing tools for user-friendly real-time analytics. METHODS: The system combines in-memory capabilities (based on QlikView software) with innovative techniques that compress the complexity of the data, consequently improving its readability as well as its accessibility for designated end users. Aside from the technical and conceptual components, the software's implementation necessitated a complex system of permission and governance. RESULTS: A continuously running system including daily updates with a user-friendly Web interface and real-time usage was established. This paper introduces its main components and major design ideas. A commented video summarizing and presenting the work can be found within the Multimedia Appendix. CONCLUSIONS: The system has been well-received by a focus group of physicians within an initial prerollout. Aside from improving data transparency, the system's main benefits are its quality and process control capabilities, knowledge discovery, and hypothesis generation. Limitations such as run time, governance, or misinterpretation of data are considered.

Long-Term Monitoring of the Internal Energy Distribution of Isolated Cluster Systems.

A method is presented to monitor the internal energy distribution of cluster anions via delayed electron detachment by pulsed photoexcitation and demonstrated on Co_{4}^{-} in an electrostatic ion beam trap. In a cryogenic operation, we calibrate the detachment delay to internal energy. By laser frequency scans, at room temperature, we reconstruct the time-dependent internal energy distribution of the clusters. The mean energies of ensembles from a cold and a hot ion source both approach thermal equilibrium. Our data yield a radiative emission law and the absorptivity of the cluster for thermal radiation.

Innovative in Situ Ball Mill for X-ray Diffraction.

The renewed interest of mechanochemistry as an ecofriendly synthetic route has inspired original methodologies to probe reactions, with the aim to rationalize unknown mechanisms. Recently, Friscic et al. ( Nat. Chem. 2013 , 5 , 66 - 73 , DOI: 10.1038/nchem.1505 ) monitored the progress of milling reactions by synchrotron X-ray powder diffraction (XRPD). For the first time, it was possible to acquire directly information during a mechanochemical process. This new methodology is still in its early stages, and its development will definitively transform the fundamental understanding of mechanochemistry. A new type of in situ ball mill setup has been developed at the Materials Science beamline (Swiss Light Source, Paul Scherrer Institute, Switzerland). Its particular geometry, described here in detail, results in XRPD data displaying significantly lower background and much sharper Bragg peaks, which in turn allow more sophisticated analysis of mechanochemical processes, extending the limits of the technique.

[The first KiGGS follow-up (KiGGS Wave 1): study conduct, sample design, and response]. / Die erste KiGGS-Folgebefragung (KiGGS Welle 1): Studiendurchführung, Stichprobendesign und Response.

The "German Health Interview and Examination Survey for Children and Adolescents" (KiGGS) is part of the health monitoring system of the Robert Koch Institute (RKI). Following the KiGGS baseline study (2003 - 06), which comprised interviews and physical examinations of 0- to 17-year-old participants, KiGGS Wave 1 (2009 - 2012) was carried out as a telephone-based survey. In addition to providing longitudinal data, a second essential aim of KiGGS is to regularly provide population-based cross-sectional data on the health situation of children and adolescents aged 0-17 years living in Germany. Therefore, the study population of KiGGS Wave 1 consists of re-invited participants from the baseline study (KiGGS cohort), supplemented by newly invited children aged 0-6 years. The newly invited participants were randomly chosen from local population registries in the 167 baseline sample points. This method was chosen to supplement the sample with younger age groups. This article focuses on the age groups from 0 to 17 years, which are relevant for prevalence estimations among children and adolescents. In total 12,368 children and adolescents took part; among them 4,455 newly invited and 7,913 re-invited participants (response 38.8 and 72.9%, respectively). A comparison of the net sample with the resident German population (0-17 years) regarding particular population characteristics and an analysis of the relationship between the re-participation rate and certain characteristics collected in the baseline study (7-17 years) suggest a mostly unbiased sample. To account for certain aspects of the population and nonresponse, cross-sectional and trend analyses were partially corrected by weighting factors.

German health interview and examination survey for adults (DEGS) - design, objectives and implementation of the first data collection wave.

BACKGROUND: The German Health Interview and Examination Survey for Adults (DEGS) is part of the recently established national health monitoring conducted by the Robert Koch Institute. DEGS combines a nationally representative periodic health survey and a longitudinal study based on follow-up of survey participants. Funding is provided by the German Ministry of Health and supplemented for specific research topics from other sources. METHODS/DESIGN: The first DEGS wave of data collection (DEGS1) extended from November 2008 to December 2011. Overall, 8152 men and women participated. Of these, 3959 persons already participated in the German National Health Interview and Examination Survey 1998 (GNHIES98) at which time they were 18-79 years of age. Another 4193 persons 18-79 years of age were recruited for DEGS1 in 2008-2011 based on two-stage stratified random sampling from local population registries. Health data and context variables were collected using standardized computer assisted personal interviews, self-administered questionnaires, and standardized measurements and tests. In order to keep survey results representative for the population aged 18-79 years, results will be weighted by survey-specific weighting factors considering sampling and drop-out probabilities as well as deviations between the design-weighted net sample and German population statistics 2010. DISCUSSION: DEGS aims to establish a nationally representative data base on health of adults in Germany. This health data platform will be used for continuous health reporting and health care research. The results will help to support health policy planning and evaluation. Repeated cross-sectional surveys will permit analyses of time trends in morbidity, functional capacity levels, disability, and health risks and resources. Follow-up of study participants will provide the opportunity to study trajectories of health and disability. A special focus lies on chronic diseases including asthma, allergies, cardiovascular conditions, diabetes mellitus, and musculoskeletal diseases. Other core topics include vaccine-preventable diseases and immunization status, nutritional deficiencies, health in older age, and the association between health-related behavior and mental health.

Specifically Increased Rate of Infections in Children Post Measles in a High Resource Setting.

Objectives: Post-measles increased susceptibility to subsequent infections seems particularly relevant in low-resource settings. We tested the hypothesis that measles causes a specifically increased rate of infections in children, also in a high-resource setting. Methods: We conducted a retrospective cohort study on a large measles outbreak in Berlin, Germany. All children with measles who presented to hospitals in Berlin were included as cases, children with non-infectious and children with non-measles infectious diseases as controls. Repeat visits within 3 years after the outbreak were recorded. Results: We included 250 cases, 502 non-infectious, and 498 infectious disease controls. The relative risk for cases for the diagnosis of an infectious disease upon a repeat visit was 1.6 (95% CI 1.4-2.0, p < 0.001) vs. non-infectious and 1.3 (95% CI 1.1-1.6, p = 0.002) vs. infectious disease controls. 33 cases (27%), 35 non-infectious (12%) and 57 (18%) infectious disease controls presented more than three times due to an infectious disease (p = 0.01, and p = 0.02, respectively). This results in a relative risk of more than three repeat visits due to an infection for measles cases of 1.8 (95% CI 1.3-2.4, p = 0.01), and 1.4 (95% CI 1.0-1.9, p = 0.04), respectively. Conclusion: Our study demonstrates for the first time in a high-resource setting, that increased post-measles susceptibility to subsequent infections in children is measles-specific-even compared to controls with previous non-measles infections.

Corrigendum: Specifically increased rate of infections in children post measles in a high resource setting.

[This corrects the article DOI: 10.3389/fped.2022.896086.].

Fragmentation channels in dissociative electron recombination with hydronium and other astrophysically important species.

We report on our recent studies of dissociative recombination (DR) employing two different fragment imaging detection techniques at the TSR storage ring in Heidelberg, Germany. Principles of an upgraded 3D optical system and the new energy-sensitive multistrip detector (EMU) are explained together with possible applications in reaction dynamics studies. With the EMU imaging detector we succeeded to observe the branching ratios after DR of deuterated hydronium ions D(3)O(+) at energies of 0-0.5 and 4-21 eV. The branching ratios are almost constant at low energies while above 6 eV both oxygen-producing channels O + D + D + D and O + D(2) + D strongly increase and dominate by about 85% at 11 eV. To demonstrate further capabilities of our fragment imaging detectors, we also summarize some of our additional recent studies on DR of molecular ions important for astrophysics as well as for fundamental unimolecular dynamics.

Phytoplankton thermal responses adapt in the absence of hard thermodynamic constraints.

To better predict how populations and communities respond to climatic temperature variation, it is necessary to understand how the shape of the response of fitness-related rates to temperature evolves (the thermal performance curve). Currently, there is disagreement about the extent to which the evolution of thermal performance curves is constrained. One school of thought has argued for the prevalence of thermodynamic constraints through enzyme kinetics, whereas another argues that adaptation can-at least partly-overcome such constraints. To shed further light on this debate, we perform a phylogenetic meta-analysis of the thermal performance curves of growth rate of phytoplankton-a globally important functional group-controlling for environmental effects (habitat type and thermal regime). We find that thermodynamic constraints have a minor influence on the shape of the curve. In particular, we detect a very weak increase of maximum performance with the temperature at which the curve peaks, suggesting a weak "hotter-is-better" constraint. Also, instead of a constant thermal sensitivity of growth across species, as might be expected from strong constraints, we find that all aspects of the thermal performance curve evolve along the phylogeny. Our results suggest that phytoplankton thermal performance curves adapt to thermal environments largely in the absence of hard thermodynamic constraints.

Hypoxio: a simple solution to preventing pericellular hypoxia in cell monolayers growing at physiological oxygen levels.

Culturing cells as adherent monolayers is a common approach in cell biology. For cell culture experiments to yield reliable results it is important to replicate in vivo conditions as faithfully as possible. Increasingly, researchers appreciate the importance of oxygen in cell physiology and the corresponding need to maintain physiologically relevant oxygen levels during experiments. However, although oxygen levels are sometimes monitored over the course of an experiment, this is virtually always in the incubator gas phase and not in the media bathing cells. When incubator oxygen levels are set to a physiologically appropriate level, typically 2-6%, the pericellular oxygen levels experienced by cells may be substantially lower, particularly under conditions where cells are respiring rapidly. We have developed a simple approach to prevent this problem. 'Hypoxio' is a software application that uses real time measurements of pericellular oxygen to coordinate media mixing via a tilt table. Hypoxio allows the user to set a threshold below which it initiates a mixing cycle of user-adjustable duration to abolish standing gradients associated with pericellular hypoxia. Here we describe Hypoxio, demonstrate its efficacy, and direct the reader to our GitHub site for downloadabale software and a description of hardware.

Health inequalities among children and adolescents in Germany. Developments over time and trends from the KiGGS study.

This study examines the extent to which health inequalities among children and adolescents in Germany have developed over the past decade. The analyses are based on data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), which are representative of the 0- to 17-year-old population in Germany. The KiGGS data were collected in three waves: the KiGGS baseline study (2003-2006), KiGGS Wave 1 (2009-2012) and KiGGS Wave 2 (2014-2017). Prevalences of five health outcomes are considered: general health, mental health problems, physical activity, the consumption of sugary soft drinks, and smoking. Moreover, it defines health inequalities in relation to differences in the socioeconomic status of the family (SES), an index derived from the parents' level of education, occupation and income, and considers both absolute and relative health inequalities. In order to do so, the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII) were calculated using linear probability or log-binomial models. Significant inequalities were identified to the detriment of young people from families with a low SES. These inequalities were particularly pronounced in the KiGGS Wave 2 data with regard to general health and the consumption of sugary soft drinks. Additionally, evidence from trend analyses for these two outcomes suggests that relative inequalities have increased. However, absolute inequalities decreased during the same period, and this also applies to smoking. The persistently high and, in some cases, widened levels of health inequalities indicate that adolescents from families with a low SES do not benefit to the same extent from disease prevention and health promotion measures for children and adolescents as young people from families with a higher SES.

The challenge of comprehensively mapping children's health in a nation-wide health survey: design of the German KiGGS-Study.

BACKGROUND: From May 2003 to May 2006, the Robert Koch Institute conducted the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Aim of this first nationwide interview and examination survey was to collect comprehensive data on the health status of children and adolescents aged 0 to 17 years. METHODS/DESIGN: Participants were enrolled in two steps: first, 167 study locations (sample points) were chosen; second, subjects were randomly selected from the official registers of local residents. The survey involved questionnaires filled in by parents and parallel questionnaires for children aged 11 years and older, physical examinations and tests, and a computer assisted personal interview performed by study physicians. A wide range of blood and urine testing was carried out at central laboratories. A total of 17 641 children and adolescents were surveyed - 8985 boys and 8656 girls. The proportion of sample neutral drop-outs was 5.3%. The response rate was 66.6%. DISCUSSION: The response rate showed little variation between age groups and sexes, but marked variation between resident aliens and Germans, between inhabitants of cities with a population of 100 000 or more and sample points with fewer inhabitants, as well as between the old West German states and the former East German states. By analysing the short non-responder questionnaires it was proven that the collected data give comprehensive and nationally representative evidence on the health status of children and adolescents aged 0 to 17 years.

KiGGS Wave 2 cross-sectional study - participant acquisition, response rates and representativeness.

For the third time, wave 2 of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), which is conducted in the context of health monitoring at the Robert Koch Institute, now provides representative cross-sectional data for Germany. Completed in 2017, data for the cross-sectional component of KiGGS Wave 2 was collected in the form of an interview and examination survey. Interview survey data was collected from 15,023 participants, meaning that the required number of participants has been reached. A randomly selected subgroup of 3,567 participants was also examined. The overall response rate was 40.1%. Differences in response rates were registered regarding certain sociodemographic characteristics. Weighting was applied to compensate for differences in willingness to participate related to age, gender, geographic region, nationality and education factors. Weighting ensures that assessments of the health of children and adolescents in Germany are representative for the population. The data serves to estimate prevalence rates and, through comparison with the results from previous survey waves, to analyse trends. A set of measures were taken to recruit a sufficiently large group of participants and ensure that the net sample reflects the composition of the overall population to the highest degree. For future surveys, further measures ought to be taken in order to improve the integration of hard-to-reach subgroups.

KiGGS Wave 2 longitudinal component - data collection design and developments in the numbers of participants in the KiGGS cohort.

The German Health Interview and Examination Survey for Children and Adolescents (KiGGS) is conducted within the health monitoring framework that has been established at the Robert Koch Institute (RKI). In addition to regular cross-sectional studies of the current health of children and adolescents living in Germany, KiGGS also includes a longitudinal component - the KiGGS cohort. The longitudinal data, which can be linked individually throughout the various waves of the study, enables developments in health and their associated influencing factors to be analysed during the life course. Participants from the KiGGS baseline study form the baseline of the KiGGS cohort. The baseline study was carried out between 2003 and 2006 as a nationwide interview and examination survey of children and adolescents aged between 0 and 17 years. The KiGGS cohort comprises the 17,641 participants who, after taking part in the baseline study, also agreed to participate in recurring follow-ups that are to continue through adolescence into adulthood. Until now, two follow-up studies have been conducted: KiGGS Wave 1 (2009-2012, n=11,992) and KiGGS Wave 2 (2014-2017), which, in line with the baseline study, was conducted as an interview and examination survey. A total of 10,853 repeat participants were interviewed for KiGGS Wave 2; 6,465 people also took part in an examination. As such, 61.3% of the people who originally participated in the baseline study also provided data from interviews for KiGGS Wave 2. In addition, 50.8% have provided various forms of data for all three of the survey's waves. This data pool can help answer numerous questions from the epidemiological life course discipline regarding the population living in Germany; at the time of the baseline study, these participants were children and adolescents. In order to exploit the full potential of the study for life course research and to be able to trace the health and social development of different generations in the future, the concepts on which the study is based are to be further developed, and innovative strategies for participant retention are to be drawn up.

New data for action. Data collection for KiGGS Wave 2 has been completed.

The fieldwork of the second follow-up to the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) was completed in August 2017. KiGGS is part of the Robert Koch Institute's Federal Health Monitoring. The study consists of the KiGGS cross-sectional component (a nationally representative, periodic cross-sectional survey of children and adolescents aged between 0 and 17) and the KiGGS cohort (the follow-up into adulthood of participants who took part in the KiGGS baseline study). KiGGS collects data on health status, health-related behaviour, psychosocial risk and protective factors, health care and the living conditions of children and adolescents in Germany. The first interview and examination survey (the KiGGS baseline study; undertaken between 2003 and 2006; n=17,641; age range: 0-17) was carried out in a total of 167 sample points in Germany. Physical examinations, laboratory analyses of blood and urine samples and various physical tests were conducted with the participants and, in addition, all parents and participants aged 11 or above were interviewed. The first follow-up was conducted via telephone-based interviews (KiGGS Wave 1 2009-2012; n=11,992; age range: 6-24) and an additional sample was included (n=4,455; age range: 0-6). KiGGS Wave 2 (2014-2017) was conducted as an interview and examination survey and consisted of a new, nationwide, representative cross-sectional sample of 0- to 17-year-old children and adolescents in Germany, and the second KiGGS cohort follow-up. The completion of the cross-sectional component of KiGGS Wave 2 means that the health of children and adolescents in Germany can now be assessed using representative data gained from three study waves. Trends can therefore be analysed over a period stretching to over ten years now. As the data collected from participants of the KiGGS cohort can be individually linked across the various surveys, in-depth analyses can be conducted for a period ranging from childhood to young adulthood and developmental processes associated with physical and mental health and the associated risk and protective factors can be explored. As such, KiGGS Wave 2 expands the resources available to health reporting, as well as policy planning and research, with regard to assessing the health of children and adolescents in Germany.

Systemic inflammatory response syndrome after acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: The role of inflammation in patients with coronary artery disease is emerging. We sought to assess the profile and outcomes of patients with a clinical syndrome of severe systemic inflammation that led to a diagnosis of suspected sepsis in the setting of acute myocardial infarction complicated by cardiogenic shock (CS). METHODS: Patients enrolled in the randomized SHOCK (SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK) trial (n = 302) were divided into those with clinical signs of severe systemic inflammation (eg, fever [94%] or leukocytosis [72%]) that led to a diagnosis of suspected sepsis (n = 54 [18%]) and those without suspected sepsis (controls; n = 243 [80%]). The patients with suspected sepsis were then further subdivided into those who were considered to be potentially infectious (positive culture result ["culture-positive"]; n = 40) and those who were not (negative culture result ["culture-negative"]; n = 14). RESULTS: Severe systemic inflammation was diagnosed 4 and 2 days after the onset of CS in culture-positive and culture-negative patients, respectively. Patients who developed systemic inflammation tended to be younger (P = .05) and to have lower systemic vascular resistance (SVR) near the onset of CS (P = .006). Many culture-positive patients (40%) had undergone coronary artery bypass graft surgery. However, the lower the initial SVR, the higher the risk of developing culture-positive systemic inflammation (P = .01), even after controlling for age and coronary artery bypass graft surgery. A time-dependent model, adjusted for age, showed that culture-positive patients were at significantly higher risk for death than were controls (hazard ratio, 2.22; 95% confidence interval, 1.32-3.76; P = .008). CONCLUSIONS: Almost one fifth of patients with acute myocardial infarction complicated by CS showed clinical signs of severe systemic inflammation, and those who were culture-positive for sepsis had twice the risk of death. The observation of lower SVR at the onset of shock in patients who subsequently had culture-positive systemic inflammation suggests that inappropriate vasodilation may play an important role in the pathogenesis and persistence of shock and in the risk of infection.

Pneumococcal Vertebral Osteomyelitis after Epidural Injection: A Rare Event.

Streptococcus pneumoniae vertebral infections have rarely been reported. Herein, we report a case of pneumococcal vertebral osteomyelitis with paraspinal and epidural abscesses as well as concomitant bacteremia following epidural injection. This will be the second case in the literature reporting pneumococcal vertebral osteomyelitis related to epidural manipulation.

Ambovex(®) as a novel immunological modulator drug for the treatment of hepatocellular carcinoma (HCC) in the liver: a Phase II clinical trial.

Hepatocellular carcinoma (HCC) is a global public health problem, based on it being the fifth most common cancer and third leading cause of cancer-related mortality worldwide. The approved conventional treatment methods for HCC have shown life-threatening side effects with limited or negligible success, especially in multifocal HCC. As a consequence, new therapeutic approaches are being explored, including immunoregulatory molecules that may have the potential to treat or delay the progression of HCC. A novel pharmaceutical botanical drug - Ambovex(®), an immune-modulator molecule - was tested to treat or delay the progress of HCC. We conducted a 6-month randomized clinical trial with an additional 3-month washing period (no treatment) to evaluate the safety and efficacy of low-dose Ambovex oral spray in treating patients with HCC. The clinical study involved a total of 40 patients, with 33 in the treatment group and seven in the control group. The α-fetoprotein (AFP) levels were measured every month and ultrasound scans were performed at time zero and every 2 months thereafter. Computed tomography (CT) scans were performed for patients in the treatment group. Ambovex proved to be safe, as there were no significant side effects although some patients found that the drug has unpleasant taste. AFP analysis showed a significant decrease in its level (α=0.05; 95% confidence interval) in the treatment group when compared to the control group at 3 months (P=0.0031) and at 6 months (P=0.007). The ultrasound results showed improvement in the treated group, as evidenced by a significant decrease in the lesion numbers and sizes. The lesions in 38% of treated patients decreased from multiple to single with major improvements; 35% of patients exhibited a decrease from multiple lesions to multiple lesions with minor improvements, whereas 27% had stabilized lesions. CT scans in the treated group showed significant improvement, as there was complete disappearance of the lesions after 6 months of treatment with Ambovex in two patients. This clinical study showed the effective and promising results of Ambovex as an immunological modulator in treating HCC. Further exploration of Ambovex is recommended.