bluuebunny/crossref_metadata_2025 huggingface dataset:
100 years of inherited metabolic disorders in Austria—A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021
Authors: Ramoser Gabriele , Caferri Federica , Radlinger Bernhard , Brunner‐Krainz Michaela , Herbst Sybille , Huemer Martina , Hufgard‐Leitner Miriam , Kircher Susanne G. , Konstantopoulou Vassiliki , Löscher Wolfgang , Möslinger Dorothea , Plecko Barbara , Spenger Johannes , Stulnig Thomas , Sunder‐Plassmann Gere , Wortmann Saskia , Scholl‐Bürgi Sabine , Karall Daniela ,   Austrian IMD Registry Group
Published: October 2021

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare disorders characterized by disruption of metabolic pathways. To date, data on incidence and prevalence of IMDs are limited. Taking advantage of a functioning network within the Austrian metabolic group, our registry research aimed to update the data of the “Registry for Inherited Metabolic Disorders” started between 1985 and 1995 with retrospectively retrieved data on patients with IMDs according to the Society for the Study of Inborn Errors of Metabolism International Classification of Diseases 11 (SSIEM ICD11) catalogue. Included in this retrospective register were 2631 patients with an IMD according to the SSIEM ICD11 Classification, who were treated in Austria. Thus, a prevalence of 1.8/10 000 for 2020 and a median minimal birth prevalence of 16.9/100 000 (range 0.7/100 000‐113/100 000) were calculated for the period 1921 to February 2021. We detected a male predominance (m:f = 1.2:1) and a mean age of currently alive patients of 17.6 years (range 5.16 months‐100 years). Most common diagnoses were phenylketonuria (17.7%), classical galactosaemia (6.6%), and biotinidase deficiency (4.2%). The most common diagnosis categories were disorders of amino acid and peptide metabolism (819/2631; 31.1%), disorders of energy metabolism (396/2631; 15.1%), and lysosomal disorders (395/2631; 15.0%). In addition to its epidemiological relevance, the “Registry for Inherited Metabolic Disorders” is an important tool for enhancing an exchange between care providers. Moreover, by pooling expertise it prospectively improves patient treatment, similar to pediatric oncology protocols. A substantial requirement for ful filling this goal is to regularly update the registry and provide nationwide coverage with inclusion of all medical specialties.
A General Model to Calculate the Spin–Lattice Relaxation Rate (R1) of Blood, Accounting for Hematocrit, Oxygen Saturation, Oxygen Partial Pressure, and Magnetic Field Strength Under Hyperoxic Conditions
Authors: Bluemke Emma , Stride Eleanor , Bulte Daniel P.
Published: October 2021

Background

Under normal physiological conditions, the spin–lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen‐enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects.

Purpose

To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO2, PO2, and B0 under both normal physiological and hyperoxic conditions.

Study Type

Mathematical modeling.

Population

One hundred and twenty‐six published values of R1 from phantoms and animal models.

Field Strength/Sequence

5–8.45 T.

Assessment

We propose a two‐compartment nonlinear model to calculate R1 as a function of hematocrit, PO2, and B0. The Akaike Information Criterion (AIC) was used to select the best‐performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO2, and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO2 > 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R2), and Bland–Altman analysis. The effect of volume fraction constants and was assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO2, and PO2 of the literature data points.

Statistical Tests

Bland–Altman, AIC, MSE, coefficient of determination (R2), SD.

Results

The model estimates agreed well with the literature values of R1 of blood (R2 = 0.93, MSE = 0.0013 s−2), and its performance was consistent across the range of parameters: B0 = 1.5–8.45 T, SO2 = 0.40–1, PO2 = 30–700 mmHg.

Data Conclusion

Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen‐enhanced MRI and oxygen‐delivery experiments.

Level of Evidence

3

Technical Efficacy

Stage 1
Development of monolith/aminated carbon nanotubes composite‐based solid‐phase microextraction of phenoxycarboxylic acids herbicides in water and soil samples
Authors: Chen Hexun , Luo Siyu , Huang Xiaojia
Published: October 2021

In this study, a new adsorbent based on monolith/aminated carbon nanotubes composite was facilely prepared and employed as the extraction phase of multiple monolithic fibers solid‐phase microextraction for the capture of phenoxycarboxylic acids herbicides. The adsorbent was fabricated by mingling aminated carbon nanotubes in the poly (allylthiourea‐co‐ethylene glycol dimethacrylate) monolith. Various techniques were employed to characterize the morphology, structure, and pore size of the prepared adsorbent. The proposed microextraction method displayed satisfactory capture performance towards studied analytes through multi‐interactions such as hydrogen‐bonding, hydrophobic and π‐π interactions. Under the optimized conditions, a sensitive and reliable method to quantify trace analytes in water and soil samples was developed. The limits of detection were in the ranges of 0.13–0.25 μg/L and 0.20–0.61 μg/kg for water and soil samples, respectively. The practicality of the introduced method was demonstrated by applying it to monitor the contents of studied analytes in environmental water and soil samples. Satisfactory fortified recoveries (76.4–119%) and reproducibility were obtained. The achieved results well demonstrated that the suggested microextraction technique can efficiently extract phenoxycarboxylic acids and the developed method exhibits a promising potential for reliable and sensitive quantification of trace analytes in complex samples.
Two temperate corals are tolerant to low pH regardless of previous exposure to natural CO2 vents
Authors: Carbonne Chloe , Teixidó Núria , Moore Billy , Mirasole Alice , Guttierez Thomas , Gattuso Jean‐Pierre , Comeau Steeve
Published: October 2021

Ocean acidification is perceived to be a major threat for many calcifying organisms, including scleractinian corals. Here, we investigate (1) whether past exposure to low pH environments associated with CO2 vents could increase corals tolerance to low pH and (2) whether zooxanthellate corals are more tolerant to low pH than azooxanthellate corals. To test these hypotheses, two Mediterranean colonial corals Cladocora caespitosa (zooxanthellate) and Astroides calycularis (azooxanthellate) were collected from CO2 vents and reference sites and incubated in the laboratory under present day (pH on the total scale, pHT 8.07) and low pH conditions (pHT 7.70). Rates of net calcification, dark respiration, and photosynthesis were monitored during a 6‐month experiment. Monthly net calcification was assessed every 27–35 d using the buoyant weight technique, whereas light and dark net calcification was estimated using the alkalinity anomaly technique during 1‐h incubations. Neither species showed any change in net calcification rates, respiration, and photosynthesis regardless of their environmental history, pH treatment, and trophic strategy. Our results indicate that C. caespitosa and As. calycularis could tolerate future ocean acidification conditions for at least 6 months. These results will aid in predicting species' future responses to ocean acidification, and thus improve the management and conservation of Mediterranean corals.
CEO overconfidence and corporate tournaments
Authors: Vitanova Ivana
Published: October 2021

Can CEO overconfidence help explain pay inequalities in top management teams? Tournament literature argues that pay gaps between different executive echelons increase competition among executives in the goal to replace the incumbent CEO and by so doing incentivize all top management team members to provide more effort. The increase in incentives can in turn lead to firm‐level performance improvement especially in corporations where agency conflicts are severe. However, entrenchment seeking CEOs can be reluctant to this kind of incentivizing mechanisms. In this paper, we model such a context and show how overconfident CEOs are more likely to administer tournament‐like incentives than realistic CEOs. Hence, we describe a novel and underexplored way in which CEO overconfidence can be beneficial to shareholders.
Modeling and analysis of nonlinear tumor‐immune interaction under chemotherapy and radiotherapy
Authors: Bashkirtseva Irina , Chukhareva Anna , Ryashko Lev
Published: October 2021

This paper examines the effects of treatment on tumor‐immune dynamics based on a conceptual two‐dimensional model. In absence of treatment, this model exhibits regimes of “active” and “dormant” tumor. Increasing intensity of chemotherapy entails a significant complication of tumor‐immune interaction with parameter zones of monostability, bistability, and tristability where “active,” “dormant,” and “zero” tumor states can coexist. A detailed description of bifurcations, attractors, and their basins is given. Based on this mathematical analysis, we discuss efficiency of various programs of treatment combining chemotherapy and radiotherapy.
The Human Dimensions of Recreational Anglers Targeting Freshwater Species in Coastal Ecosystems, with Implications for Management
Authors: Koemle Dieter , Beardmore Ben , Dorow Malte , Arlinghaus Robert
Published: October 2021

Little is known about whether brackish coastal ecosystems attract specific angler types that are characterized by site-specific preferences and behaviors while targeting freshwater fishes living in a low-salinity environment. Using the lagoon (“Bodden”) fisheries in northeastern Germany, we compared the human dimensions among anglers fishing in Bodden sites, anglers fishing primarily in freshwater sites, and other, less-setting-specialized anglers that use both marine and freshwater fisheries. Data were generated from a 1-year telephone–mail–diary study involving over 1,000 study participants. The general characteristics, demographics, specialization level, motives, catch orientation, and catch-and-release behaviors of the three angler groups were rather similar. However, when targeting specific freshwater fish (i.e., Eurasian Perch Perca fluviatilis, Northern Pike Esox lucius, and Zander [also known as Pikeperch] Sander lucioperca), the motives of anglers choosing the Bodden versus freshwater sites differed. Specifically, Bodden anglers targeting freshwater species in brackish waters were more catch oriented, trophy fish oriented, and challenge seeking compared to freshwater anglers. Bodden anglers were also more likely to fish with friends rather than alone compared to the other angler groups, and they were more likely to use motorboats and to take guides compared to freshwater anglers. Correspondingly, a revealed preference choice model showed that anglers expecting high catch outcomes and social experiences with friends and boat fishing were more likely to select the Bodden waters relative to freshwater sites. Additionally, anglers with a stronger orientation toward the noncatch, experience-based aspects of fishing were more likely to fish in the Bodden and coastal sites compared to freshwater, suggesting that coastal sites satisfy both catch- and non-catch-related expectations. We suggest that given their specific preferences and characteristics, Bodden anglers will be particularly sensitive to constraints imposed on using motorboats and to declines in catch rates and trophy sizes in the catch, specifically for Northern Pike.
A computational intelligence based maximum power point tracking for photovoltaic power generation system with small‐signal analysis
Authors: Senapati Manoj Kumar , Pradhan Chittaranjan , Calay Rajnish Kaur
Published: October 2021

There are multiple peak functions in its output power characteristic curve of a photovoltaic (PV) array under partial shading conditions (PSCs), the perturb and observe (P&O) may fail to track the global maximum power point (GMPP). Therefore, a reliable maximum power point tracking (MPPT) technique is essential to track the GMPP within an appropriate time. This article proposes a hybrid technique by combining an evolutionary optimization technique, namely the modified invasive weed optimization (MIWO) with the conventional P&O algorithm to enhance the search performance for the maximum power output of the PV system. MIWO executes in the initial stages of the tracking followed by the P&O at the final stages in the MPPT search process. The combined approach ensures faster convergence and better search to the GMPP under rapid climate change and PSCs. The search performance of the hybrid MIWO+P&O technique is examined on a standalone PV system through both MATLAB/Simulink environment and experimentally using dSPACE (DS1103)‐based real‐time microcontroller hardware setup. The performance of the proposed hybrid MPPT scheme is compared with the recent state‐of‐the‐art MPPPT techniques. In addition, the small‐signal analysis of the PV system is carried out to evaluate the loop robustness of the controller design. For a given set of system parameters, simulations for the small‐signal model and robustness studies are analyzed to verify the results. The overall results justify the efficacy of the proposed hybrid MPPT algorithm.
Biophysical characterization of full‐length oleosin in dodecylphosphocholine micelles
Authors: Julien Jeffrey A. , Mutchek Sarah G. , Wittenberg Nathan J. , Glover Kerney Jebrell
Published: October 2021

Oleosin is a hydrophobic protein that punctuates the surface of plant seed lipid droplets, which are 20 nm–100 μm entities that serve as reservoirs for high‐energy metabolites. Oleosin is purported to stabilize lipid droplets, but its exact mechanism of stabilization has not been established. Probing the structure of oleosin directly in lipid droplets is challenging due to the size of lipid droplets and their high degree of light scattering. Therefore, a medium in which the native structure of oleosin is retained, but is also amenable to spectroscopic studies is needed. Here, we show, using a suite of biophysical techniques, that dodecylphosphocholine micelles appear to support the tertiary structure of the oleosin protein (i.e., hairpin conformation) and render the protein in an oligomeric state that is amenable to more sophisticated biophysical techniques such as NMR.
Overexpression of ATP‐binding cassette transporter Mdr49‐like confers resistance to imidacloprid in the field populations of brown planthopper, Nilaparvata lugens
Authors: Wang Li‐Xiang , Tao Sha , Zhang Yan‐Chao , Pei Xin‐Guo , Gao Yang , Song Xin‐Yu , Yu Zhi‐Tao , Gao Cong‐Fen
Published: October 2021

BACKGROUND

The brown planthopper (BPH), Nilaparvata lugens (Stål), is the most severe pest attacking rice crops using sucking mouthparts. It causes significant damages to rice growth and food production worldwide. With the long‐term and wide use of insecticides, field populations of BPH have developed resistance to many insecticides.

RESULTS

Here, we showed that upregulation of an ATP‐binding cassette transporter gene NlMdr49‐like contributes to imidacloprid resistance in field populations of BPH. A comparative transcriptome analysis was performed to evaluate the gene expression in two field populations (JXSG18 and YNTC18). Compared with a susceptible strain (Sus), 202 upregulated genes and 170 downregulated genes were identified in both field populations. Functional enrichment analysis revealed that the differentially expressed genes (DEGs) are mainly linked to metabolic process and transmembrane transport. Among the candidate DEGs, NlMdr49‐like was significantly upregulated in both field populations. Based on the genome and transcriptome of BPH, the full‐length complementary DNA of NlMdr49‐like was sequenced and its molecular characteristics were analyzed. Expression pattern analysis of various tissues showed that NlMdr49‐like was predominantly expressed in midgut and Malpighian tubules which are important excretion organs. Knocking down NlMdr49‐like reduced BPH resistance to imidacloprid, but did not affect its resistance to the other nine insecticides (chlorpyrifos, thiamethoxam, nitenpyram, dinotefuran, sulfoxaflor, triflumezopyrim, ethiprole, buprofezin and pymetrozine). Furthermore, a transgenic strain of Drosophila melanogaster overexpressing NlMdr49‐like was less susceptible to imidacloprid.

CONCLUSIONS

Our findings indicate that upregulation of NlMdr49‐like is another mechanism contributing to imidacloprid resistance in N. lugens. This result is helpful to further understand the resistance mechanism of N. lugens to imidacloprid. © 2021 Society of Chemical Industry.
A quantitative systems pharmacology approach to predict the safe‐equivalent dose of doxorubicin in patients with cardiovascular comorbidity
Authors: Sang Lan , Yuan Yi , Zhou Ying , Zhou Zhengying , Jiang Muhan , Liu Xiaoquan , Hao Kun , He Hua
Published: October 2021

Patients with cardiovascular comorbidity are less tolerant to cardiotoxic drugs and should be treated with reduced doses to prevent cardiotoxicity. However, the safe‐equivalent dose of antitumor drugs in patients with cardiovascular disease/risk is difficult to predict because they are usually excluded from clinical trials as a result of ethical considerations. In this study, a translational quantitative system pharmacology‐pharmacokinetic‐pharmacodynamic (QSP‐PK‐PD) model was developed based on preclinical study to predict the safe‐equivalence dose of doxorubicin in patients with or without cardiovascular disease. Virtual clinical trials were conducted to validate the translational QSP‐PK‐PD model. The model replicated several experimental and clinical observations: the left ventricular ejection fraction (LVEF) was reduced and the left ventricular end‐diastolic volume (LVEDV) was elevated in systolic dysfunction rats, the LVEF was preserved and LVEDV reduced in diastolic dysfunction rats, and patients with preexisting cardiovascular disease were more vulnerable to doxorubicin‐induced cardiac dysfunction than cardiovascular healthy patients. A parameter sensitivity analysis showed that doxorubicin‐induced cardiovascular dysfunction was mainly determined by the sensitivity of cardiomyocytes to cardiotoxic drugs and the baseline value of LVEDV, reflected in LVEF change percentage from the baseline. Blood pressure was the least sensitive factor affecting doxorubicin‐induced cardiotoxicity.
Growth‐Controllable Triboelectric Nanogenerator Based on Surface‐Attached Metal‐Organic Framework Layer on Living Leaf
Authors: Li Xunjia , Jiang Chengmei , Yao Yao , Zhang Qi , Dai Shufen , Ying Yibin , Ping Jianfeng
Published: October 2021

Plant nanoelectronics aims to achieve specific functions by selecting suitable nanomaterials to connect or implant into plants. In this work, a new cyclic‐spraying method is developed to attain controllable growth of surface‐attached metal‐organic framework (SURMOF) coatings on various complex substrates, including cotton, silk, and plant leaves. The covalent bonds formed between the SURMOF layer and substrate enable them to connect firmly without additional adhesive and do not fall off from the microstructured substrate surface with the change of biological activity or environment. Noteworthily, the triboelectric polarity of SURMOF can be regulated by changing the ligand molecule. As a proof of concept, a growth‐controllable triboelectric nanogenerator (GC‐TENG) based on living leaves and coated SURMOF layer is developed, and the feasibility of using it in the self‐driven agricultural monitoring system is explored. In addition, long‐term monitoring results show that the growth of SURMOF coating will not cause damage to plant leaf tissue, nor will it affect plant photosynthesis.
Genomic prediction modeling of soybean biomass using UAV‐based remote sensing and longitudinal model parameters
Authors: Toda Yusuke , Kaga Akito , Kajiya‐Kanegae Hiromi , Hattori Tomohiro , Yamaoka Shuhei , Okamoto Masanori , Tsujimoto Hisashi , Iwata Hiroyoshi
Published: October 2021

The application of remote sensing in plant breeding can provide rich information about the growth processes of plants, which leads to better understanding concerning crop yield. It has been shown that traits measured by remote sensing were also beneficial for genomic prediction (GP) because the inclusion of remote sensing data in multitrait models improved prediction accuracies of target traits. However, the present multitrait GP model cannot incorporate high‐dimensional remote sensing data due to the difficulty in the estimation of a covariance matrix among the traits, which leads to failure in improving its prediction accuracy. In this study, we focused on growth models to express growth patterns using remote sensing data with a few parameters and investigated whether a multitrait GP model using these parameters could derive better prediction accuracy of soybean [Glycine max (L.) Merr.] biomass. A total of 198 genotypes of soybean germplasm were cultivated in experimental fields, and longitudinal changes of their canopy height and area were measured continuously via remote sensing with an unmanned aerial vehicle. Growth parameters were estimated by applying simple growth models and incorporated into the GP of biomass. By evaluating heritability and correlation, we showed that the estimated growth parameters appropriately represented the observed growth curves. Also, the use of these growth parameters in the multitrait GP model contributed to successful biomass prediction. We conclude that the growth models could describe the genetic variation of soybean growth curves based on several growth parameters. These dimension‐reduction growth models will be indispensable for extracting useful information from remote sensing data and using this data in GP and plant breeding.
GenoRisk: A polygenic risk score for Alzheimer's disease
Authors: Dickson Samuel P. , Hendrix Suzanne B. , Brown Bruce L. , Ridge Perry G. , Nicodemus‐Johnson Jessie , Hardy Marci L. , McKeany Allison M. , Booth Steven B. , Fortna Ryan R. , Kauwe John S.K. ,   NIAGADS
Published: October 2021

Introduction

Recent clinical trials are considering inclusion of more than just apolipoprotein E (APOE) ε4 genotype as a way of reducing variability in analysis of outcomes.

Methods

Case‐control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)–associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross‐validation. Genotype and sex × age estimates from the best performing model were combined with age and intercept estimates from the general population to develop a personalized genetic risk score, termed age, and sex‐adjusted GenoRisk.

Results

The elastic net model that included age, age x sex interaction, allelic APOE terms, and 29 additional SNPs performed the best. This model explained an additional 19% of the heritable risk compared to APOE genotype alone and achieved an area under the curve of 0.747.

Discussion

GenoRisk could improve the risk assessment of individuals identified for prevention studies.
‘Spoken from the Impulse of the Moment’: Epistolarity, Sensibility, and Breath in Frances Burney’s Evelina
Authors: Skinner Gillian
Published: October 2021

Skinner explores the neglected role of breath in the mapping and understanding of eighteenth-century sensibility. Thematically rich in their associations with body and spirit, life and death, breath and breathlessness are also woven into the stylistic particularities of both sentimental and epistolary fiction. Examination of the epistolarity of Evelina, and the dramatic use of dialogue Burney became known for, reveals breathlessness as the signifier of intense and instinctive moral discernment of the kind described by eighteenth-century philosophers such as Frances Hutcheson, complicating the view that the heroine of epistolary fiction more generally, and Evelina in particular, is purely passive. Instead, she emerges as actively involved in numerous scenarios that at once challenge her capacity for moral conduct and allow her to demonstrate her power to act.
Romantic Consumption: The Paradox of Fashionable Breath
Authors: Lawlor Clark
Published: October 2021

The tragic disease of consumption/tuberculosis is, perhaps notoriously, a central disease of literary and artistic international Romanticism, as well as having a profound influence in wider society. Lawlor’s essay analyses the role that breath played in this phenomenon: how could breath and breathlessness possibly contribute to the valorisation of such a horrible illness? Using literary and medical works, this analysis demonstrates that the ‘reality’ (albeit variable) of consumptive breath was often overridden, overwritten, or reframed, by cultural discourses which included religious and classical concepts of breath, new and old medical models, gender and social rank.
The Forgotten Obvious: Breathing in Psychoanalysis
Authors: Walker Oriana , Rose Arthur
Published: October 2021

This essay traces the role of breathing in the literature and history of psychoanalysis from Josef Breuer and Sigmund Freud through Otto Fenichel and Wilhelm Reich. It uncovers interesting discontinuities in the significance granted to breathing as the psychoanalytic tradition develops. These observations of the breath shed new light on major theoretical divisions of psychoanalysis from its founding through its arrival in the US with the émigré analysts. This history offers views both into the changing imagination of the breath itself and into the role of the body in an evolving psychoanalytic practice more generally.
Mobile Edge Computing
Authors: Zhang Yan
Published: October 2021

Mobile edge computing is a promising paradigm that brings computing resources to mobile users at the network edge, allowing computing-intensive and delay-sensitive applications to be quickly processed by edge servers to satisfy the requirements of mobile users. In this chapter, we first introduce a hierarchical architecture of mobile edge computing that consists of a cloud plane, an edge plane, and a user plane. We then introduce three typical computation offloading decisions. Finally, we review state-of-the-art works on computation offloading and present the use case of joint computation offloading.
Thermalization in large-N CFTs
Authors: Karlsson Robin , Parnachev Andrei , Tadić Petar
Published: October 2021

In d-dimensional CFTs with a large number of degrees of freedom an important set of operators consists of the stress tensor and its products, multi stress tensors. Thermalization of such operators, the equality between their expectation values in heavy states and at finite temperature, is equivalent to a universal behavior of their OPE coefficients with a pair of identical heavy operators. We verify this behavior in a number of examples which include holographic and free CFTs and provide a bootstrap argument for the general case. In a free CFT we check the thermalization of multi stress tensor operators directly and also confirm the equality between the contributions of multi stress tensors to heavy-heavy-light-light correlators and to the corresponding thermal light-light two-point functions by disentangling the contributions of other light operators. Unlike multi stress tensors, these light operators violate the Eigenstate Thermalization Hypothesis and do not thermalize.
A dynamic model for viscoelasticity in domains with time-dependent cracks
Authors: Sapio Francesco
Published: October 2021

In this paper, we prove the existence of solutions for a class of viscoelastic dynamic systems on time-dependent cracking domains.
Verlorene Lebensjahre: Bekanntes und Neues zur Methodik am Beispiel der häufigsten Todesursachen in Deutschland
Authors: Hübner Joachim , Mattutat Johann , Katalinic Alexander
Published: October 2021

Hintergrund

Verlorene Lebensjahre (Years of Life Lost, YLL) sind ein aussagekräftiger, in Deutschland jedoch wenig verwendeter Indikator für die Relevanz von Todesursachen. Es existieren zahlreiche Methoden, mit denen YLL berechnet werden können.

Ziel der Arbeit

Es werden prototypische Methoden zur Berechnung von YLL vorgestellt und kritisch eingeordnet. Auf dieser Basis wird eine verbesserte Methode vorgeschlagen, die auf der Nutzung von todesursachenbereinigten Sterbetafeln (Cause-Elimination Life Tables, CELT) beruht.

Methoden

Etablierte Methoden und die hier vorgeschlagene Modifikation werden auf die Sterblichkeit in Deutschland 2018 angewandt. Veränderungen gegenüber 1998 werden anhand der modifizierten Methode dargestellt.

Ergebnisse

Während nach der Zahl der Sterbefälle Herz-Kreislauf-Erkrankungen im Jahr 2018 die bedeutendste Todesursache waren, war Krebs für die meisten YLL verantwortlich. Unterschiedliche Methoden zur Berechnung der YLL führen zu deutlich abweichenden Rängen bei den weniger bedeutsamen Todesursachen. YLL auf Basis von allgemeinen Sterbetafeln unterschätzen die YLL auf Basis der todesursachenbereinigten Sterbetafeln um bis zu 18,4 % (Herz-Kreislauf-Erkrankungen). Gemessen an den CELT-basierten YLL waren im Jahr 1998 Herz-Kreislauf-Erkrankungen die bedeutsamste Todesursache.

Diskussion

Die Berechnung von YLL auf der Basis von todesursachenbereinigten Sterbetafeln vermeidet Inkonsistenzen etablierter Methoden und führt zu relevant abweichenden Ergebnissen. Besonderheiten der vorgeschlagenen Methode (Verstoß gegen das Egalitätsprinzip, fehlende Additivität) beeinträchtigen ihren Nutzen als Instrument zur Steuerung der Gesundheitsversorgung nicht.
Population pharmacokinetics of cefotaxime in intensive care patients
Authors: Swartling Maria , Smekal Anna-Karin , Furebring Mia , Lipcsey Miklos , Jönsson Siv , Nielsen Elisabet I.
Published: October 2021

Purpose

To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates.

Methods

This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000–3000 mg given 2–6 times daily), were collected from the first day of treatment for up to three consecutive days. In total, 263 cefotaxime samples were included in the population pharmacokinetic analysis.

Results

A two-compartment model with linear elimination, proportional residual error and inter-individual variability (IIV) on clearance and central volume of distribution best described the data. The typical individual was 64 years, with body weight at ICU admission of 92 kg and estimated creatinine clearance of 94 mL/min. The resulting typical value of clearance was 11.1 L/h, central volume of distribution 5.1 L, peripheral volume of distribution 18.2 L and inter-compartmental clearance 14.5 L/h. The estimated creatinine clearance proved to be a significant covariate on clearance (p < 0.001), reducing IIV from 68 to 49%.

Conclusion

A population pharmacokinetic model was developed to describe cefotaxime pharmacokinetics and associated variability in adult ICU patients. The estimated creatinine clearance partly explained the IIV in cefotaxime clearance. However, the remaining unexplained IIV is high and suggests a need for dose individualisation using therapeutic drug monitoring where the developed model, after evaluation of predictive performance, may provide support.
Anthropometry of the proximal femur and femoral head in children/adolescents using three-dimensional computed tomography-based measurements
Authors: Darwich Ali , Geiselhardt Christiane , Bdeir Mohamad , Janssen Sonja , Schoenberg Stefan O. , Gravius Sascha , Jawhar Ahmed
Published: October 2021

Purpose

Defining normal anthropometric ranges of proximal femur and femoral head for each age group in children/adolescents is a necessity when differentiating normal anatomical variants from pathological deformities. Aim of this study is to define a set of normal anthropometric parameters based on 3D-CT measurements in normal asymptomatic children/adolescents and analyse the variations arising depending on age, side, and/or gender.

Methods

Morphology of the proximal femur was retrospectively assessed in 170 hips (85 children, < 15 years). Measurements included covered femoral head volume (CFHV), femoral head diameter (FHD), femoral head extrusion index (FHEI), coronal alpha angle (CAA), lateral centre-edge angle (LCEA), anterior (AOS) and posterior head-neck offset (POS) and femoral neck-shaft angle (FNSA). Correlation analyses as well as inter- and intra-rater reliability were performed.

Results

CFHV, LCEA, FHD and AOS/POS increased with age and FHEI, CAA, and FNSA decreased with age. None of the measurements correlated with the side. AOS showed a poor correlation with gender. Rapid growth phases were observed at the age of 1, 7 and 11. The inter- and intra-rater reliability was high (range ICC 0.8–0.99 Cronbach alpha 0.86–0.99).

Conclusion

This data delivers a description of growth phases as well as gender and age-correlated reference values of the proximal femoral morphology that could be used by paediatricians and orthopaedic/paediatric surgeons to early diagnose proximal femur deformities and provide guidance in the planning of possible operations.
Experimental investigation of the transonic buffet cycle on a supercritical airfoil
Authors: D’Aguanno A. , Schrijer F. F. J. , van Oudheusden B. W.
Published: October 2021

Transonic buffet behaviour of the supercritical airfoil OAT15A was investigated experimentally at flow conditions$$Ma=0.7$$Ma=0.7and$$\alpha =3.5^\circ $$α=3.5∘, using schlieren and particle image velocimetry (PIV). The general behaviour of the buffet cycle was characterised with short-exposure schlieren visualisation and phase-averaged PIV measurements. A spectral analysis showed that the shock oscillation occurs with a dominant contribution at 160 Hz (St = 0.07, in good agreement with the literature) and between 25 and 55 % of the chord of the airfoil. Proper Orthogonal Decomposition (POD) was applied to the PIV data to extract the main modes connected with buffet. It is found that the first three most energetic modes capture around 65 % of the total fluctuating kinetic energy. The first and the third modes have a main frequency peak at 160 Hz and are well representing the separated area and the shock oscillation. The second mode was, instead, associated with an asymmetrical behaviour of the separated area and of the shear layer and displays a main peak at 320 Hz, being double the main buffet cycle frequency. Finally, it was shown that by using the 11 most energetic POD modes, an accurate reduced-order model (ROM) is obtained, which when subtracted from the instantaneous velocity fields allows the visualisation of the small-scale structures present in the flow, such as the upstream travelling waves (UTWs) and the vortex shedding in the separated area near the trailing edge. The analysis allowed to estimate the velocity of the UTWs, obtaining values in good agreement with the literature. In contrast, the analysis of the vortex dynamics in the trailing edge area revealed that vortices shed at the shock foot, which convect downstream in an area detached from the airfoil surface, cannot be considered responsible for the creation of UTWs in view of the mismatch in frequency of the two phenomena.

Graphic abstract
Cardiac acoustic biomarkers as surrogate markers to diagnose the phenotypes of pulmonary hypertension: an exploratory study
Authors: Yamakawa Nobuhide , Kotooka Norihiko , Kato Tomoyuki , Kuroda Tatsuhiko , Node Koichi
Published: October 2021

Pulmonary hypertension (PH) is commonly associated with left heart disease. In this retrospective study, using the database of a clinical study conducted between January 2008 and July 2008, the phenotypes of PH were classified using non-invasive cardiac acoustic biomarkers (CABs) and compared with classification by echocardiography. Records with same-day measurement of acoustic cardiography and right heart catheterization (RHC) parameters were included; cases with congenital heart disease were excluded. Using the RHC measurements, PH was classified as pre-capillary PH (Prec-PH), isolated post-capillary PH (Ipc-PH), and combined pre-capillary and post-capillary PH (Cpc-PH). The first, second, third, and fourth heart sounds (S1, S2, S3, and S4) were quantified as CABs (intensity, complexity, and strength). Forty subjects were selected: 5 had Prec-PH, 5 had Ipc-PH, 8 had Cpc-PH, and 22 had No-PH. CABs were significantly correlated with RHC measurements, with significant differences among phenotypes. Phenotype classification was performed using various CABs, and the diagnostic performance as assessed by the area under the receiver operating characteristic curve was 0.674–0.720 for Prec-PH, 0.657–0.807 for Ipc-PH, and 0.742 for Cpc-PH. High negative and low positive predictive values for phenotype identification were observed. CABs may provide an ambulatory measurement method with home-monitoring friendliness which is more convenient than standard examinations to identify presence of PH and its phenotypes.
Surgery due to mechanical bowel obstruction in relapsed ovarian cancer: clinical and surgical results of a bicentric analysis of 87 patients
Authors: Armbrust R. , Chekerov R. , Sander S. , Biebl M. , Chopra S. , Krell Jonathan , Rinne Natasha , Nixon Katherine , Fotopoulou C. , Sehouli J.
Published: October 2021

Introduction

Mechanical bowel obstruction is a frequent acute and life-threatening event in relapsed ovarian cancer. Salvage surgery after failure of all conservative approaches, resulting in short bowel syndrome (SBS) constitutes a therapeutic dilemma. Our aim was to evaluate patients’ surgical and clinical outcome in these highly palliative situations. Previous, limited, data reported a high morbidity and mortality. However, recent surgical and therapeutical improvements in relapsed ovarian cancer (ROC) offer better identification of patients who might benefit from surgery in an effort to extend the window of opportunity to subsequently offer these patients novel systemic therapeutic approaches.

Material and methods

All subsequent ROC patients between 2012 and 2017 with acute mechanical bowel obstruction who underwent salvage extraperitoneal en bloc intestinal resection were retrospectively identified. Data were collected from two ESGO certified Ovarian Cancer Centers of Excellence (Charité Berlin and Imperial College London) and systematically evaluated regarding surgical and clinical outcomes.

Results

Overall, 87 ROC patients were included in the analysis (median age 56 years, range 24–88), 47% were platinum resistant. High grade serous was the most common histology (76%) while most of the patients (67%) had at least two previous lines of treatment. Mean observed OS was 7.8 months. After salvage surgery, 46% of the patients had a residual small bowel length < 180 cm and 18% > 180 cm resulting in 41% in need of total parental nutrition. In 80% of the patients a permanent stoma was necessary. 30d morbidity and mortality was 74% and 10%, respectively. More than half of the patients were able to receive further courses of chemotherapy after surgery.

Discussion

Salvage surgery for bowel obstruction in ROC patients needs careful consideration and identification of optimal surgical candidates to have the maximal therapeutic benefit. Despite the challenging morbidity profile, most patients managed to proceed to subsequent novel and conventional systemic treatment and so have their window of therapeutic opportunity extended.
Ischemic preconditioning of the muscle reduces the metaboreflex response of the knee extensors
Authors: Angius Luca , Pageaux Benjamin , Crisafulli Antonio , Hopker James , Marcora Samuele Maria
Published: October 2021

Purpose

This study investigated the effect of ischemic preconditioning (IP) on metaboreflex activation following dynamic leg extension exercise in a group of healthy participants.

Method

Seventeen healthy participants were recruited. IP and SHAM treatments (3 × 5 min cuff occlusion at 220 mmHg or 20 mmHg, respectively) were administered in a randomized order to the upper part of exercising leg’s thigh only. Muscle pain intensity (MP) and pain pressure threshold (PPT) were monitored while administrating IP and SHAM treatments. After 3 min of leg extension exercise at 70% of the maximal workload, a post-exercise muscle ischemia (PEMI) was performed to monitor the discharge group III/IV muscle afferents via metaboreflex activation. Hemodynamics were continuously recorded. MP was monitored during exercise and PEMI.

Results

IP significantly reduced mean arterial pressure compared to SHAM during metaboreflex activation (mean ± SD, 109.52 ± 7.25 vs. 102.36 ± 7.89 mmHg) which was probably the consequence of a reduced end diastolic volume (mean ± SD, 113.09 ± 14.25 vs. 102.42 ± 9.38 ml). MP was significantly higher during the IP compared to SHAM treatment, while no significant differences in PPT were found. MP did not change during exercise, but it was significantly lower during the PEMI following IP (5.10 ± 1.29 vs. 4.00 ± 1.54).

Conclusion

Our study demonstrated that IP reduces hemodynamic response during metaboreflex activation, while no effect on MP and PPT were found. The reduction in hemodynamic response was likely the consequence of a blunted venous return.
Novel gene discovery for hearing loss and other routes to increased diagnostic rates
Authors: Kremer Hannie
Published: October 2021

Despite decades of research, there is much to be learned about the genetic landscape of sensorineural hearing loss. Novel genes for hearing loss remain to be identified while ‘secrets’ of the known genes need to be uncovered. These ‘secrets’ include regulatory mechanisms of gene activity and novel aspects of gene structure. To obtain a more complete picture of the genetics of hearing loss, the available experimental and bioinformatic tools need to be fully exploited. This is also true for data resources such as ENCODE. For the inner ear, however, such data resources and analytical tools need to be developed or extended. Collaborative studies provide opportunities to achieve this and to optimally use those tools and resources that are already available. This will accelerate the discoveries that are necessary for improving molecular genetic diagnostics and genetic counselling and for the development of therapeutic strategies.
Skeleton-based human activity recognition using ConvLSTM and guided feature learning
Authors: Yadav Santosh Kumar , Tiwari Kamlesh , Pandey Hari Mohan , Akbar Shaik Ali
Published: October 2021

Human activity recognition aims to determine actions performed by a human in an image or video. Examples of human activity include standing, running, sitting, sleeping,etc. These activities may involve intricate motion patterns and undesired events such as falling. This paper proposes a novel deep convolutional long short-term memory (ConvLSTM) network for skeletal-based activity recognition and fall detection. The proposed ConvLSTM network is a sequential fusion of convolutional neural networks (CNNs), long short-term memory (LSTM) networks, and fully connected layers. The acquisition system applies human detection and pose estimation to pre-calculate skeleton coordinates from the image/video sequence. The ConvLSTM model uses the raw skeleton coordinates along with their characteristic geometrical and kinematic features to construct the novel guided features. The geometrical and kinematic features are built upon raw skeleton coordinates using relative joint position values, differences between joints, spherical joint angles between selected joints, and their angular velocities. The novel spatiotemporal-guided features are obtained using a trained multi-player CNN-LSTM combination. Classification head including fully connected layers is subsequently applied. The proposed model has been evaluated on the KinectHAR dataset having 130,000 samples with 81 attribute values, collected with the help of a Kinect (v2) sensor. Experimental results are compared against the performance of isolated CNNs and LSTM networks. Proposed ConvLSTM have achieved an accuracy of 98.89% that is better than CNNs and LSTMs having an accuracy of 93.89 and 92.75%, respectively. The proposed system has been tested in realtime and is found to be independent of the pose, facing of the camera, individuals, clothing,etc. The code and dataset will be made publicly available.
Konzepte zur Integration von Flexibilitäten in Wohn- und Nichtwohngebäuden in ein dynamisches Lastmanagement
Authors: Becker Michael , Müller Tobias , Forchheim Maximilian Hendrik , Cano-Tirado David , Zdrallek Markus
Published: October 2021

Dieser Artikel stellt die Konzepte zweier Add-on-Systeme für Verteilnetzautomatisierungssysteme vor, deren Ziel die Nutzung neuer Netzaktoren, wie die Ladeinfrastruktur für Elektrofahrzeuge, elektrische Wärmepumpen und Batteriespeicher, als Flexibilitäten für ein dynamisches und marktorientiertes Netzengpassmanagement ist.

Die entwickelten Konzepte legen dabei jeweils den Fokus auf den regulierten Bereich des Netzbetreibers (Fokus des Projektes ElCiN) und den freien Marktbereich der Anschlussnehmer (Fokus des Projektes InFleX), ohne die jeweiligen Anforderungen des anderen Bereichs außer Acht zu lassen.

Das im ElCiN-Projekt entwickelte Gesamtkonzept, welches den zellularen Ansatz des VDE umsetzt (VDE Verband der Elektrotechnik Elektronik Informationstechnik e.V., Zellulares Energiesystem: Ein Beitrag zur Konkretisierung des zellularen Ansatzes mit Handlungsempfehlungen, https://www.vde.com/resource/blob/1884494/98f96973fcdba70777654d0f40c179e5/studie---zellulares-energiesystem-data.pdf2019), ermöglicht ein vollautomatisiertes und marktorientiertes Netzengpassmanagement. Dabei wurde ein Datenaustausch zwischen reguliertem Bereich und Marktbereich definiert, der einzelne neue Netzaktoren, aber auch in Zellen zusammengefasste und ggf. optimierte Netzaktoren, in das Netzengpassmanagement integrieren kann.

Das InFleX-Projekt beschäftigt sich mit der Hebung der Flexibilitäten für (Nicht-) Wohngebäude und deren energetischen Optimierung und Flexibilitätsbereitstellung für Verteilnetzautomatisierungssysteme.

Beide entwickelten Konzepte sowie die daraus entstandenen Systeme können grundsätzlich zu einem Gesamtsystem zusammengefasst werden. Ein solches Gesamtsystem setzt dann nicht nur den zellularen Ansatz des VDE um, sondern tut dies unter Berücksichtigung der Anforderungen und Interessen des Netzbetreibers sowie des Anschlussnehmers.