bluuebunny/crossref_metadata_2025 huggingface dataset:
A risk evaluation method for deformation monitoring systems
Authors: Zaminpardaz S. , Teunissen P. J. G. , Tiberius C. C. J. M.
Published: February 2020

In this contribution, we propose a method for statistically evaluating the risk in a deformation monitoring system. When the structure under monitoring moves beyond tolerance, the monitor system should issue an alert. Only a very small probability is acceptable of the system telling us that no change beyond a critical threshold has taken place, while in reality it has. This probability is referred to asintegrity risk. We provide a formulation of integrity risk where the interaction between estimation and testing is taken into account, implying the use of conditional probabilities. In doing so, we assumed different scenarios with the alerts being dependent on both the identified hypothesis and the threat that the estimated size of deformations entails. It is hereby highlighted that a correct risk evaluation requires estimation and testing being considered together, as they are typically intimately linked. In practice, one may, however, find it simpler computation-wise to neglect the estimation–testing link. For this case, we provide an approximation of the integrity risk. This approximation may provide a too optimistic or pessimistic description of the integrity risk depending on the testing procedure and tolerances of the structure at hand. Monitoring systems, besides issuing timely alerts, are also required to provide threat estimates together with their corresponding probabilistic properties. As the testing outcome determines how the threat gets estimated, the threat estimator will then inherit the statistical properties of both estimation and testing. We derive the threat estimator$$\bar{b}_{j}$$b¯jand its probability density function, taking the contributions from combined estimation and testing into account. It is highlighted that although the threat estimator under the identified hypothesis$${\mathcal {H}}_{j}$$Hj, i.e.,$$\hat{b}_{j}$$b^j, is normally distributed, the estimator$$\bar{b}_{j}$$b¯jis not. It is explained that working with$$\hat{b}_{j}$$b^jinstead of$$\bar{b}_{j}$$b¯j, thus ignoring the estimation–testing link, may provide a too optimistic description of the threat estimator’s quality. The presented method is illustrated by means of two simple deformation examples.
Current and future requirements to industrial analytical infrastructure—part 1: process analytical laboratories
Authors: Eisen Kristina , Eifert Tobias , Herwig Christoph , Maiwald Michael
Published: February 2020

The competitiveness of the chemical and pharmaceutical industry is based on ensuring the required product quality while making optimum use of plants, raw materials, and energy. In this context, effective process control using reliable chemical process analytics secures global competitiveness. The setup of those control strategies often originate in process development but need to be transferable along the whole product life cycle. In this series of two contributions, we want to present a combined view on the future of PAT (process analytical technology), which is projected in smart labs (part 1) and smart sensors (part 2). In laboratories and pilot plants, offline chemical analytical methods are frequently used, where inline methods are also used in production. Here, a transferability from process development to the process in operation would be desirable. This can be obtained by establishing PAT methods for production already during process development or scale-up. However, the current PAT (Bakeev 2005, Org Process Res 19:3–62; Simon et al. 2015, Org Process Res Dev 19:3–62) must become more flexible and smarter. This can be achieved by introducing digitalization-based knowledge management, so that knowledge from product development enables and accelerates the integration of PAT. Conversely, knowledge from the production process will also contribute to product and process development. This contribution describes the future role of the laboratory and develops requirements therefrom. In part 2, we examine the future functionality as well as the ingredients of a smart sensor aiming to eventually fuel full PAT functionality—also within process development or scale-up facilities (Eifert et al. 2020, Anal Bioanal Chem).
Revisiting the estimation of cutting power with different energetic methods while sawing soft and hard woods on the circular sawing machine: a Central European case
Authors: Orlowski Kazimierz A. , Ochrymiuk Tomasz , Hlaskova Ludka , Chuchala Daniel , Kopecky Zdenek
Published: February 2020

In the classical approaches, used in Central Europe in practice, cutting forces and cutting power in sawing processes of timber are commonly computed by means of the specific cutting resistancekc. It needs to be highlighted that accessible sources in handbooks and the scientific literature do not provide any data about wood provenance, nor about cutting conditions, in which cutting resistance has been empirically determined. In the analyses of sawing processes, the use of a model with elements of fracture mechanics involved is an alternative way. In this work, predictions of the newly developed model (FRAC_MOD) for the circular sawing machine are presented. Thanks to this modern approach, it was possible to reveal the usefulness of the FRAC_MOD, using experimental results data on fracture toughness and shear yield stresses of both Polish pine (Pinus sylvestrisL.) and Czech beech wood (Fagus sylvaticaL.). The achieved results were compared to the forecasted values obtained with classical models (CLAS_PL and CLAS_CZ), which are commonly applied in Central European sawmills. The carried out analyses allowed us to discover undesired effects in the form of underestimation of cutting power when applying the CLAS_PL and CLAS_CZ models. For that reason, the FRAC_MOD cutting model could be suggested for the prediction of energetic effects in cases of dynamical analyses and even unsteady cases.
The splenium of the corpus callosum: embryology, anatomy, function and imaging with pathophysiological hypothesis
Authors: Blaauw J. , Meiners L. C.
Published: February 2020

Background and purpose

The splenium of the corpus callosum is the most posterior part of the corpus callosum. Its embryological development, anatomy, vascularization, function, imaging of pathology, possible pathophysiological mechanisms by which pathology may develop and the clinical consequences are discussed.

Methods

A literature-based description is provided on development, anatomy and function. MR and CT images are used to demonstrate pathology. The majority of pathology, known to affect the splenium, and the clinical effects are described in three subsections: (A) limited to the splenium, with elaboration on pathophysiology of reversible splenial lesions, (B) pathology in the cerebral white matter extending into or deriving from the splenium, with special emphasis on tumors, and (C) splenial involvement in generalized conditions affecting the entire brain, with a hypothesis for pathophysiological mechanisms for the different diseases.

Results

The development of the splenium is preceded by the formation of the hippocampal commissure. It is bordered by the falx and the tentorium and is perfused by the anterior and posterior circulation. It contains different caliber axonal fibers and the most compact area of callosal glial cells. These findings may explain the affinity of specific forms of pathology for this region. The fibers interconnect the temporal and occipital regions of both hemispheres reciprocally and are important in language, visuospatial information transfer and behavior. Acquired pathology may lead to changes in consciousness.

Conclusion

The development, location, fiber composition and vascularization of the splenium make it vulnerable to specific pathological processes. It appears to play an important role in consciousness.
Imaging of cerebral complications of extracorporeal membrane oxygenation in infants with congenital heart disease — ultrasound with multimodality correlation
Authors: Svrckova Patricia , Meshaka Riwa , Holtrup Melanie , Aramburo Angela , Mankad Kshitij , Kazmi Farhat , Owens Catherine M. , Gala-Peralta Sandra , Semple Thomas
Published: February 2020

Cranial ultrasound on neonatal intensive care units is generally performed by intensive care physicians, but radiologists often provide this crucial bedside test to children on specialist paediatric cardiac intensive care units. On a paediatric cardiac intensive care unit, complex congenital cardiac conditions are commonly encountered in both pre- and postoperative scenarios, often with the use of extracorporeal membrane oxygenation (ECMO), which both increases the risks of a number of neurologic complications and results in significant changes in vascular physiology. The aim of this pictorial essay is to discuss cranial ultrasound technique, demonstrate the changes in Doppler flow profiles resulting from veno-arterial extracorporeal membrane oxygenation and congenital cardiac conditions, and illustrate commonly encountered intracranial complications of extracorporeal membrane oxygenation support in congenital cardiac care.
Noninvasive evaluation of renal oxygenation in children with chronic kidney disease using blood-oxygen-level-dependent magnetic resonance imaging
Authors: Luo Fenglan , Liao Yi , Cui Kunhua , Tao Yuhong
Published: February 2020

Background

Renal hypoxia is considered a final pathway in the progression of chronic kidney disease (CKD). Blood-oxygen-level-dependent magnetic resonance imaging (BOLD-MRI) has shown merit for evaluating renal oxygenation in adults.

Objective

To investigate renal cortical and medullary R2* values by CKD stage and by renal function index in children with chronic kidney disease.

Materials and methods

Twenty-one children with CKD Stage 1–3, 16 children with CKD Stage 4–5, and 6 healthy volunteers underwent a renal MRI using multigradient recalled-echo sequence with 16 echoes. We measured the R2* values of the renal cortex and medulla on BOLD-MRI.

Results

The cortical R2* value was ranked as CKD Stage 4–5 > CKD Stage 1–3 > healthy controls, and the medullary R2* value was ranked as CKD Stage 4–5 > CKD Stage 1–3. There was no significant difference in the medullary R2* value between CKD Stage 1–3 patients and the healthy controls. There was a positive correlation between the R2* values in the renal cortex (r=0.73) and medulla (r=0.89), and the serum creatinine level (P<0.001), and the renal cortical and medullary R2* values were negatively correlated with the estimated glomerular filtration rate (r=–0.71 and r=–0.89, respectively; P<0.001).

Conclusion

BOLD-MRI might contribute to noninvasive assessment of renal oxygenation in children with CKD in vivo but it did not reflect renal function in our sample.
Lessons from a multicentre retrospective study of peptide receptor radionuclide therapy combined with lanreotide for neuroendocrine tumours: a need for standardised practice
Authors: Prasad Vikas , Srirajaskanthan Raj , Toumpanakis Christos , Grana Chiara Maria , Baldari Sergio , Shah Tahir , Lamarca Angela , Courbon Frédéric , Scheidhauer Klemens , Baudin Eric , Truong Thanh Xuan-Mai , Houchard Aude , Dromain Clarisse , Bodei Lisa
Published: February 2020

Purpose

PRELUDE aimed to assess use and effectiveness/safety of lanreotide autogel/depot (LAN) combined with 177Lu-DOTATOC or 177Lu-DOTATATE (LAN–peptide receptor radionuclide therapy [PRRT]) in patients with progressive neuroendocrine tumours (NETs).

Methods

International, non-interventional, retrospective, non-comparative analysis of medical records from patients with progressive metastatic or locally advanced grade 1 or 2 gastroenteropancreatic (GEP)- or lung-NETs. The primary endpoint was progression-free survival (PFS) at end of last LAN–PRRT cycle. Secondary endpoints included PFS at last available follow-up, best overall response, objective response rate (ORR), presence and severity of diarrhoea and flushing, and safety. Post-hoc analyses were conducted to determine pre-treatment tumour growth rate (TGR) cutoffs that best predicted the ORR during treatment.

Results

Forty patients were enrolled (GEP-NETs, n = 39; lung-NETs, n = 1). PFS rates were 91.7% at end of last LAN–PRRT cycle and 95.0% at last available follow-up. In the full analysis set, best overall response among patients with GEP-NETs (n = 23) was stable disease (n = 14, 60.9%), partial response (n = 8, 34.8%) and progressive disease (n = 1, 4.3%). The ORR was 27.3% at end of last LAN–PRRT cycle and 36.8% at last available follow-up. Optimal baseline TGR cutoffs for predicting ORR at these time points were 1.18% and 0.33%, respectively. At baseline, 81.0% of patients had diarrhoea or flushing; both remained stable or improved in most cases. No increased adverse drug reactions were reported.

Conclusion

Despite the major recruitment shortfall for the PRELUDE study, effectiveness data were encouraging in this selected population, highlighting the potential usefulness and feasibility of LAN combined with and after PRRT in patients with GEP-NETs. The study also identified challenges associated with evaluating clinical practice in a rare-disease setting and highlighted the need for standardisation of PRRT procedures.

Trial registration

Trial number: NCT02788578; URL: https://clinicaltrials.gov/ct2/show/NCT02788578
Serum immunoglobulin G4 in Sjögren’s syndrome: a pilot study
Authors: Maślińska Maria , Wojciechowska Bożena , Mańczak Małgorzata , Kwiatkowska Brygida
Published: February 2020

Immunoglobulin IgG4 plays a role in the pathogenesis of the Mikulicz disease previously considered a form of primary Sjögren's syndrome (pSS). We investigated serum levels of IgG4, total IgG, C3, and C4 serum complementary components in patients suspected of Sjögren’s syndrome. Basic laboratory and immunological tests, including IgG4 and IgG concentration, were performed on 20 healthy and 68 suspected of pSS individuals. We distinguished: group I: 48 pSS patients; group II (sicca): 20 patients with dryness without pSS. We revealed: statistical differences between groups I and II concerning hypergammaglobulinemia, ESR, RF, ANA, Ro, and La antibodies; lower IgG4 levels and IgG4/IgG ratio in group I compared to healthy individuals (p < 0.0435; 0.0035, respectively); no significant differences in the concentrations of IgG4 and IgG4/IgG ratio between sicca and control groups. significantly lower (p < 0.0002) C4 levels in group I compared to other groups; significant differences in C4 concentration and IgG4/IgG ratio between three groups (p = 0.0002 and p = 0.0090, respectively); a weak negative correlation between C4 and IgG (r =− 0.274) in the whole database; weak positive correlation between C4 and IgG4/IgG ratio (r = 0.237); a negative correlation of IgG4, IgG4/Ig ratio and C4 with focus score (r = − 0.281; r = − 0.327; r = − 0.406, respectively). IgG4 serum levels were significantly decreased compared to healthy subjects. IgG4 and C4 levels correlated with infiltrations in minor salivary glands. Hypergammaglobulinemia and decreased serum C4 component levels are typical for pSS.
A simplified ICA-based local similarity stereo matching
Authors: Chen Suting , Zhang Jinglin , Jin Meng
Published: February 2020

Since the existing stereo matching methods may fail in the regions of non-textures, boundaries and tiny details, a simplified independent component correlation algorithm (ICA)-based local similarity stereo matching algorithm is proposed. In order to improve the DispNetC, the proposed algorithm first offers the simplified independent component correlation algorithm (SICA) cost aggregation. Then, the algorithm introduces the matching cost volume pyramid, which simplifies the pre-processing process for the ICA. Also, the SICA loss function is defined. Next, the region-wise loss function combined with the pixel-wise loss function is defined as a local similarity loss function to improve the spatial structure of the disparity map. Finally, the SICA loss function is combined with the local similarity loss function, which is defined to estimate the disparity map and to compensate the edge information of the disparity map. Experimental results on KITTI dataset show that the average absolute error of the proposed algorithm is about 37% lower than that of the DispNetC, and its runtime consuming is about 0.6 s lower than that of GC-Net.
Lateralization of increased density of Iba1-immunopositive microglial cells in the anterior midcingulate cortex of schizophrenia and bipolar disorder
Authors: Petrasch-Parwez Elisabeth , Schöbel Andreas , Benali Alia , Moinfar Zahra , Förster Eckart , Brüne Martin , Juckel Georg
Published: February 2020

There is increasing evidence from genetic, biochemical, pharmacological, neuroimaging and post-mortem studies that immunological dysregulation plays a crucial role in the pathogenesis of psychoses. The involvement of microglia in schizophrenia and bipolar disorder (BD) has remained controversial, however, since results from various post-mortem studies are still inconclusive. Here, we analyzed the estimated density of microglia of age-matched individuals with schizophrenia (n = 17), BD (n = 13), and non-psychiatric control subjects (n = 17) in the anterior midcingulate cortex (aMCC), a brain area putatively involved in the pathogenesis of psychoses, using ionized calcium binding adaptor molecule 1 (Iba1)—immunohistochemistry. The microglial cells displayed a homogenously distributed Iba1—staining pattern in the aMCC with slightly varying activation states in all three groups. The estimated microglial densities did not differ significantly between individuals with schizophrenia, BD and control subjects. Remarkably, when both hemispheres were investigated separately within the three groups, the density was significantly lateralized towards the right aMCC in schizophrenia (p = 0.01) and—even more evident—in BD subjects (p = 0.008). This left–right lateralization was not observed in the control group (p = 0.52). Of note, microglial density was significantly lower in BD individuals who did not commit suicide compared with BD individuals who died from suicide (p = 0.002). This difference was not observed between individuals with BD who committed suicide and controls. The results, tentatively interpreted, suggest a hitherto unknown increased lateralization of microglial density to the right hemisphere in both psychiatric groups. If confirmed in independent samples, lateralization should be considered in all post-mortem studies on microglia. Density differences between suicide and non-suicide individuals needs further elucidation.
Functional connectivity correlates of infant and early childhood cognitive development
Authors: Bruchhage Muriel M. K. , Ngo Giang-Chau , Schneider Nora , D’Sa Viren , Deoni Sean C. L.
Published: February 2020

Childhood is defined by the development of cognitive abilities as well as brain growth and function. While prior neuroimaging studies have investigated early development fragmentally, we studied the typical development of functional network connectivity continuously from infancy to childhood (average of 24 months) in 196 singleton term born children, as well as their emergence with age and visual, motor, and language abilities as assessed using the Mullen Scales of Early Learning. We demonstrate a cross-age shift to networks linked to higher-order cognitive processes, paralleling previous findings about developmental courses of functional connectivity networks. When investigating skill associations with functional connectivity independent of age, we revealed distinct network connectivity patterns for visual, motor, and language skills as each of them become more and more refined along childhood development. Specifically, the amount of functional networks recruited increases with skill complexity, with an exceeding involvement of higher order networks enabling daily maintenance and coordination of cognitive functions. Further, both motor and language network connectivity patterns overlapped in network connectivity patterns for the default mode, visual, salience, and dorsal attention networks, possibly implicating their overarching contribution to each other’s and higher cognitive development.
Neuroanatomical tract-tracing techniques that did go viral
Authors: Lanciego Jose L. , Wouterlood Floris G.
Published: February 2020

Neuroanatomical tracing methods remain fundamental for elucidating the complexity of brain circuits. During the past decades, the technical arsenal at our disposal has been greatly enriched, with a steady supply of fresh arrivals. This paper provides a landscape view of classical and modern tools for tract-tracing purposes. Focus is placed on methods that have gone viral, i.e., became most widespread used and fully reliable. To keep an historical perspective, we start by reviewing one-dimensional, standalone transport-tracing tools; these including today’s two most favorite anterograde neuroanatomical tracers such asPhaseolus vulgaris-leucoagglutinin and biotinylated dextran amine. Next, emphasis is placed on several classical tools widely used for retrograde neuroanatomical tracing purposes, where Fluoro-Gold in our opinion represents the best example. Furthermore, it is worth noting that multi-dimensional paradigms can be designed by combining different tracers or by applying a given tracer together with detecting one or more neurochemical substances, as illustrated here with several examples. Finally, it is without any doubt that we are currently witnessing the unstoppable and spectacular rise of modern molecular-genetic techniques based on the use of modified viruses as delivery vehicles for genetic material, therefore, pushing the tract-tracing field forward into a new era. In summary, here, we aim to provide neuroscientists with the advice and background required when facing a choice on which neuroanatomical tracer—or combination thereof—might be best suited for addressing a given experimental design.
A rigorous derivation of mean-field models describing 2D micro phase separation
Authors: Niethammer Barbara , Oshita Yoshihito
Published: February 2020

We study the free boundary problem describing the micro phase separation of diblock copolymer melts in the regime that one component has small volume fraction$$\rho $$ρsuch that the micro phase separation results in an ensemble of small disks of one component. We consider the two dimensional case in this paper, whereas the three dimensional case was already considered in Niethammer and Oshita (Calc Var PDE 39:273–305, 2010). Starting from the free boundary problem restricted to disks we rigorously derive the heterogeneous mean-field equations on a time scale of the order of$${\mathcal {R}}^{3}\ln (1/\rho )$$R3ln(1/ρ), where$${\mathcal {R}}$$Ris the mean radius of disks. On this time scale, the evolution is dominated by coarsening and stabilization of the radii of the disks, whereas migration of disks becomes only relevant on a larger time scale.
Smell and taste in cervical dystonia
Authors: Herr Thorsten , Hummel Thomas , Vollmer Marcus , Willert Carsten , Veit Birgitt , Gamain Julie , Fleischmann Robert , Lehnert Bernhard , Mueller Jan-Uwe , Stenner Andrea , Kronenbuerger Martin
Published: February 2020

The pathophysiology of cervical dystonia is not completely understood. Current concepts of the pathophysiology propose that it is a network disorder involving the basal ganglia, cerebellum and sensorimotor cortex. These structures are primarily concerned with sensorimotor control but are also involved in non-motor functioning such as the processing of information related to the chemical senses. This overlap lets us hypothesize a link between cervical dystonia and altered sense of smell and taste. To prove this hypothesis and to contribute to the better understanding of cervical dystonia, we assessed olfactory and gustatory functioning in 40 adults with idiopathic cervical dystonia and 40 healthy controls. The Sniffin Sticks were used to assess odor threshold, discrimination and identification. Furthermore, the Taste Strips were applied to assess the combined taste score. Motor and non-motor deficits of cervical dystonia including neuropsychological and psychiatric alterations were assessed as cofactors for regression analyses. We found that cervical dystonia subjects had lower scores than healthy controls for odor threshold (5.8 ± 2.4 versus 8.0 ± 3.2; p = 0.001), odor identification (11.7 ± 2.3 versus 13.1 ± 1.3; p = 0.001) and the combined taste score (9.5 ± 2.2 versus 11.7 ± 2.7; p < 0.001), while no difference was found in odor discrimination (12.0 ± 2.5 versus 12.9 ± 1.8; p = 0.097). Regression analysis suggests that age is the main predictor for olfactory decline in subjects with cervical dystonia. Moreover, performance in the Montreal Cognitive Assessment is a predictor for gustatory decline in cervical dystonia subjects. Findings propose that cervical dystonia is associated with diminished olfactory and gustatory functioning.
Novel mutation of SCN9A gene causing generalized epilepsy with febrile seizures plus in a Chinese family
Authors: Zhang Tian , Chen Mingwu , Zhu Angang , Zhang Xiaoguang , Fang Tao
Published: February 2020

Generalized epilepsy with febrile seizures plus (GEFS+) is a complex familial epilepsy syndrome. It is mainly caused by mutations in SCN1A gene, encoding type 1 voltage-gated sodium channel α-subunit (NaV1.1), and GABRA1 gene, encoding the α1 subunit of the γ-aminobutyric acid type A (GABAA) receptor, while seldom related with SCN9A gene, encoding the voltage-gated sodium channel NaV1.7. In this study, we investigated a Chinese family with an autosomal dominant form of GEFS+. DNA sequencing of the whole coding region revealed a novel heterozygous nucleotide substitution (c.5873A>G) causing a missense mutation (p.Y1958C). This mutation was predicted to be deleterious by three different bioinformatics programs (The polyphen2, SIFT, and MutationTaster). Our finding reports a novel likely pathogenic SCN9A Y1958C heterozygous mutation in a Chinese family with GEFS+ and provides additional supports that SCN9A variants may be associated with human epilepsies.
Functional characterization and fitness cost of spinosad-resistant alleles in Ceratitis capitata
Authors: Guillem-Amat Ana , Ureña Enric , López-Errasquín Elena , Navarro-Llopis Vicente , Batterham Philip , Sánchez Lucas , Perry Trent , Hernández-Crespo Pedro , Ortego Félix
Published: February 2020

The sustainability of control programs for the Mediterranean fruit fly, Ceratitis capitata, for citrus crops in Spain has been threatened by the development of resistance to malathion and lambda-cyhalothrin in recent years. Spinosad is widely used without apparent loss of efficacy. However, a highly resistant strain, JW-100s, has been obtained after laboratory selection. Spinosad resistance in JW-100s has been associated with different mutant alleles of the α6 subunit of the nicotinic acetylcholine receptor (Ccα6) including an isoform-specific truncation allele, Ccα63aQ68*. Using the GAL4 > UAS system in Drosophila melanogaster to demonstrate expression of this truncated α6 subunit, in a dα6 loss-of-function genetic background, does not rescue susceptibility to spinosad, while the expression of Ccα6 wild-type isoforms does. We have also generated C. capitata isolines from JW-100s homozygous for: (1) the Ccα63aQ68*Δ3b-4 allele, which contains the mutation 3aQ68*, and (2) the Ccα63aQ68*–K352* allele, which contains the mutations 3aQ68* and K352*. Neither of these produce complete Ccα6 transcripts. The frequency of resistant alleles declined when in competition with individuals carrying the wild-type allele. Through extensive testing of both biological and behavioral fitness traits, we identified a reduced ability of Ccα63aQ68*Δ3b-4 males to detect the parapheromone and to mate with females carrying the Ccα63aQ68*–K352* allele in competition experiments. Thus, not only the potential for spontaneous resistant mutations to arise in Ccα6 but also their fitness costs must be considered when planning resistance management strategies for C. capitata.
Ticagrelor Inhibits Toll-Like and Protease-Activated Receptor Mediated Platelet Activation in Acute Coronary Syndromes
Authors: Wadowski Patricia P. , Weikert Constantin , Pultar Joseph , Lee Silvia , Eichelberger Beate , Koppensteiner Renate , Lang Irene M. , Panzer Simon , Gremmel Thomas
Published: February 2020

Purpose

Since ticagrelor inhibits the cellular uptake of adenosine, thereby increasing extracellular adenosine concentration and biological activity, we hypothesized that ticagrelor has adenosine-dependent antiplatelet properties. In the current study, we compared the effects of ticagrelor and prasugrel on platelet activation in acute coronary syndrome (ACS).

Methods

Platelet surface expression of P-selectin and activated glycoprotein (GP) IIb/IIIa in response to adenosine diphosphate (ADP), the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, the TLR-4 agonist lipopolysaccharide (LPS), the protease-activated receptor (PAR)-1 agonist SFLLRN, and the PAR-4 agonist AYPGKF were measured by flow cytometry in blood from 80 ticagrelor- and 80 prasugrel-treated ACS patients on day 3 after percutaneous coronary intervention. Residual platelet aggregation to arachidonic acid (AA) and ADP were assessed by multiple electrode aggregometry and light transmission aggregometry.

Results

ADP-induced platelet activation and aggregation, and AA-induced platelet aggregation were similar in patients on ticagrelor and prasugrel, respectively (all p ≥ 0.3). Further, LPS-induced platelet surface expression of P-selectin and activated GPIIb/IIIa did not differ significantly between ticagrelor- and prasugrel-treated patients (both p > 0.4). In contrast, Pam3CSK4-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly lower in ticagrelor-treated patients (both p ≤ 0.005). Moreover, SFLLRN-induced platelet surface expression of P-selectin and activated GPIIb/IIIa were significantly less pronounced in patients on ticagrelor therapy compared to prasugrel-treated patients (both p < 0.03). Finally, PAR-4 mediated platelet activation as assessed by platelet surface expression of activated GPIIb/IIIa following stimulation with AYPGKF was significantly lower in patients receiving ticagrelor (p = 0.02).

Conclusion

Ticagrelor inhibits TLR-1/2 and PAR mediated platelet activation in ACS patients more strongly than prasugrel.
Enforcement Intensity in Danish Drug Control, 1996–2017
Authors: Moeller Kim
Published: February 2020

Enforcement intensity towards drug law offences in Denmark has increased since 2004, making Denmark one of the few Western countries that is heading towards a more repressive drug control approach. The aim of this study is to examine patterns and correlates of drug enforcement intensity over time. Policy documents and criminal statistics on drug law offences, from 1996 to 2017, are analysed in the context of the rationality perspective and the theory of policy coherence. Time series analyses and bivariate tests of statistical significance are used to examine enforcement intensity over time, between seasons, and in the gender and ethnic composition of convictions. Three periods are identified, delineated by documents that set forth drug policy aims. From 1996 to 2003, a series of qualitative changes to the legal framework was introduced, followed by a quantitative increase in enforcement pressure from 2004 to 2010 with a focus on Copenhagen. From 2011 to 2017, other regions of the country also increased enforcement. The increased intensity in drug control followed a period of increasing cannabis prevalence rates. The increase in reported minor drug law offences correlated with increased seasonal variations and increased disparity in the gender and ethnicity of convicted individuals.
The star product in interacting quantum field theory
Authors: Hawkins Eli , Rejzner Kasia
Published: February 2020

We propose a new formula for the star product in deformation quantization of Poisson structures related in a specific way to a variational problem for a functionS, interpreted as the action functional. Our approach is motivated by perturbative algebraic quantum field theory (pAQFT). We provide a direct combinatorial formula for the star product, and we show that it can be applied to a certain class of infinite-dimensional manifolds (e.g. regular observables in pAQFT). This is the first step towards understanding how pAQFT can be formulated such that the only formal parameter is$$\hbar $$ħ, while the coupling constant can be treated as a number. In the introductory part of the paper, apart from reviewing the framework, we make precise several statements present in the pAQFT literature and recast these in the language of (formal) deformation quantization. Finally, we use our formalism to streamline the proof of perturbative agreement provided by Drago, Hack, and Pinamonti and to generalize some of the results obtained in that work to the case of a nonlinear interaction.
Winter habitat selection of Corvids in an urban ecosystem
Authors: Szala Klaudia , Dylewski Łukasz , Tobolka Marcin
Published: February 2020

Urban areas attract birds during the winter when cities provide a predictable source of food and relatively stable weather conditions. However, many other factors determine the occurrence of birds in cities. This study analysed the relationship between corvids wintering in the city of Poznań, in western Poland and habitat features. Each of 32 research site was investigated three times. The most abundant species was the rook (mean = 17.4 individuals/site); the most frequent was the Eurasian magpie (88% of all sites). To determine variables that influence the abundance of birds, a set of generalised linear models was created, with model averaging being selected for each species. The abundance of hooded crows was positively influenced by surface of parks, water and by the length of tram tracks. The number of rooks was positively linked with the number of walnut trees, garbage cans and the surface of the water and negatively linked with the length of watercourses. Jackdaw was affected positively by the number of garbage cans, the surface of the water and negatively by the cover of trees. The number of magpies was associated with the number of walnut trees, garbage cans and negatively influenced by the surface of trees. None of the investigated habitat variables significantly affected the abundance of European jay. We also found a positive correlation between the abundances of hooded crow, rook, jackdaw and magpie. The results indicate that corvids wintering in urban ecosystems exhibit selectivity toward specific habitat features and that preferences differ among the studied species.
Mathematical Modelling of Alternative Pathway of Complement System
Authors: Bakshi Suruchi , Cunningham Fraser , Nichols Eva-Maria , Biedzka-Sarek Marta , Neisen Jessica , Petit-Frere Sebastien , Bessant Christina , Bansal Loveleena , Peletier Lambertus A. , Zamuner Stefano , van der Graaf Piet H.
Published: February 2020

The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.
Automated White Matter Hyperintensity Segmentation Using Bayesian Model Selection: Assessment and Correlations with Cognitive Change
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Fiford Cassidy M. , Sudre Carole H. , Pemberton Hugh , Walsh Phoebe , Manning Emily , Malone Ian B. , Nicholas Jennifer , Bouvy Willem H , Carmichael Owen T. , Biessels Geert Jan , Cardoso M. Jorge , Barnes Josephine
Published: February 2020

Accurate, automated white matter hyperintensity (WMH) segmentations are needed for large-scale studies to understand contributions of WMH to neurological diseases. We evaluated Bayesian Model Selection (BaMoS), a hierarchical fully-unsupervised model selection framework for WMH segmentation. We compared BaMoS segmentations to semi-automated segmentations, and assessed whether they predicted longitudinal cognitive change in control, early Mild Cognitive Impairment (EMCI), late Mild Cognitive Impairment (LMCI), subjective/significant memory concern (SMC) and Alzheimer’s (AD) participants. Data were downloaded from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Magnetic resonance images from 30 control and 30 AD participants were selected to incorporate multiple scanners, and were semi-automatically segmented by 4 raters and BaMoS. Segmentations were assessed using volume correlation, Dice score, and other spatial metrics. Linear mixed-effect models were fitted to 180 control, 107 SMC, 320 EMCI, 171 LMCI and 151 AD participants separately in each group, with the outcomes being cognitive change (e.g. mini-mental state examination; MMSE), and BaMoS WMH, age, sex, race and education used as predictors. There was a high level of agreement between BaMoS’ WMH segmentation volumes and a consensus of rater segmentations, with a median Dice score of 0.74 and correlation coefficient of 0.96. BaMoS WMH predicted cognitive change in: control, EMCI, and SMC groups using MMSE; LMCI using clinical dementia rating scale; and EMCI using Alzheimer’s disease assessment scale-cognitive subscale (p < 0.05, all tests). BaMoS compares well to semi-automated segmentation, is robust to different WMH loads and scanners, and can generate volumes which predict decline. BaMoS can be applicable to further large-scale studies.
Optimal Regularity for Two-Dimensional Pfaffian Systems and the Fundamental Theorem of Surface Theory
Authors: Litzinger Florian
Published: February 2020

We prove that a Pfaffian system with coefficients in the critical space $$L^2_\mathrm {loc}$$

L
loc
2

on a simply connected open subset of $$\mathbb {R}^2$$

R

2

has a non-trivial solution in $$W^{1,2}_\mathrm {loc}$$

W
loc

1
,
2

if the coefficients are antisymmetric and satisfy a compatibility condition. As an application of this result, we show that the fundamental theorem of surface theory holds for prescribed first and second fundamental forms of optimal regularity in the classes $$W^{1,2}_\mathrm {loc}$$

W
loc

1
,
2

and $$L^2_\mathrm {loc}$$

L
loc
2

, respectively, that satisfy a compatibility condition equivalent to the Gauss–Codazzi–Mainardi equations. Finally, we give a weak compactness theorem for surface immersions in the class $$W^{2,2}_\mathrm {loc}$$

W
loc

2
,
2

.
Überlebenskünstler mit sozialen und kommunikativen Fähigkeiten
Authors: Treuner-Lange Anke , Søgaard-Andersen Lotte
Published: February 2020

Myxobacteria display complex social behaviours including formation of multicellular, spore-filled fruiting bodies. Recent research provided fascinating insights into the processes underlying these social behaviours, including intra- and intercellular signalling, motility and its regulation, and cell cycle control. These analyses also show that Myxobacteria are a rich source for the discovery of novel molecular and cellular mechanisms. VAAM (Association for General and Applied Microbiology) therefore chose Myxococcus xanthus as the Microbe of the year 2020.
RNA-Live-Imaging in Mikroorganismen
Authors: Müntjes Kira , Feldbrügge Michael
Published: February 2020

RNA live imaging is a powerful technique to visualize the subcellular localization as well as highly dynamic transport of mRNAs in vivo. Established in eukaryotic microorganisms, it is now a wide-spread system used in bacteria, animals, and plants. The method is based on the binding of heterologous RNA-binding proteins to their cognate binding sites that are integrated into the mRNA of interest. Recent advances enable the visualization of transcriptional or translational sites as well as mRNA decay.
Stop and go: Oocyten auf ihrem Weg zu einer befruchtungsfähigen Eizelle
Authors: Heim Andreas , Mayer Thomas U.
Published: February 2020

Fertilization, the fusion of the female and male gamete, is the initiating event for the development of any sexually-reproducing organism. The production of haploid gametes involves two consecutive meiotic divisions during which the diploid genome is reduced to half, creating four haploid cells. Here, we discuss how the interplay of dynamic protein phosphorylation and irreversible protein degradation drives meiotic cell cycle regulation in vertebrate oocytes.
Sexualdimorphismen adulter Stammzellen
Authors: Merten Madlen , Greiner Johannes F. W. , Kaltschmidt Christian , Kaltschmidt Barbara
Published: February 2020

Neurodegenerative diseases like Parkinson’s disease differ between the sexes in severity and occurrence. Next to hormons, increasing evidence suggests stem cell-intrinsic mechanisms to account for pathologic sex-specific differences. Here, we discuss such sex-related intrinsic mechanisms and sex-specific differences in adult stem cells, neuronal development and neuroprotection. The reviewed observations emphazise the importance of considering sexual dimorphisms for medical treatment strategies.
Ex vivo-Expansion von roten Blutzellen aus humanen Stammzellen
Authors: Dorn Isabel , Bernecker Claudia
Published: February 2020

The growing demand of blood products in modern medicine causes chronic limitations in blood supply. Current research focuses on the ex vivo production of red blood cells (RBCs) from different sources including induced pluripotent stem cells (iPSCs). RBC generation from iPSCs is limited by low effciency so far. Our group established a protocol that enables for higher cellular output and improved enucleation based on closer mimicking of the physiological microenvironment in which erythropoiesis occurs.
Unspezifische Peroxygenasen — Oxyfunktionalisierung außerhalb der Pilzhyphe
Authors: Scheibner Katrin , Ullrich René , Kiebist Jan , Kellner Harald , Hofrichter Martin
Published: February 2020

Unspecific peroxygenases (UPOs) secreted by fungi represent an intriguing enzyme type that selectively transfers peroxide-borne oxygen with high efficiency to diverse substrates including unactivated hydrocarbons. They contain a cysteine-ligated heme and catalyze hydroxylation, epoxidation, dealkylation, deacylation as well as hetero atom, halide and one-electron oxidations. Substrate spectra of UPOs resemble both those of P450 monooxygenases and heme peroxidases.
Preparedness to Implement Physical Activity and Rehabilitation Guidelines in Routine Primary Care Cancer Rehabilitation: Focus Group Interviews Exploring Rehabilitation Professionals’ Perceptions
Authors: Neher Margit , Landén Ludvigsson Maria , Enblom Anna
Published: February 2020

To explore primary care professionals’ perceptions of physical activity and other cancer rehabilitation practice in cancer survivors, investigating the preparedness to implement guidelines regarding cancer rehabilitation. We collected qualitative data through seven semi-structured focus group interviews with 48 rehabilitation professionals, with mean 9 years of experience in primary care rehabilitation (32 physiotherapists, 15 occupational therapists, and 1 rehabilitation assistant) in a primary care setting. Data was analyzed using content analysis. Primary care rehabilitation professionals expressed limited experience of cancer survivors, experienced lack of knowledge of cancer-related disability, and had doubts concerning how to treat cancer survivors. They also experienced uncertainty about where to find collaboration and support in the healthcare system outside their own rehabilitation clinic. There is a need to combine different implementation strategies to tackle multiple barriers for effective cancer survivor rehabilitation in primary care, to boost individual rehabilitation professionals’ knowledge and self-efficacy, to clarify roles and responsibilities for cancer rehabilitation across levels of care, and to develop and strengthen organizational bridges to provide adequate access to rehabilitation for cancer survivors.
Transplantable Liver Organoids, Too Many Cell Types to Choose: a Need for Scientific Self-Organization
Authors: Baptista Pedro M. , Penning Louis C.
Published: February 2020

Purpose of Review

Liver stem cells have been proposed as alternatives or additions for whole liver transplantations to accommodate the donor liver shortage. Various sources of liver stem cells have been described in experimental animal studies. Here we aim to compare the various studies.

Recent Findings

Irrespective of the experimental design, the percentage of long-lasting survival and functional recovery of transplanted cells is generally very low. An exception to this are the proliferating hepatocytes transplanted into Fah(-/-) Rag2−/−IL2rg−/− mice; here 4-month post-transplantation around 65% repopulation was observed, and 11/14 mice survived in contrast to zero survival in sham-treated animals.

Taking the different cellular sources for the organoids, the different maturation status of the transplanted cells, and the variable animal models into account, a paper-to-paper comparison is compromised. This lack of objective comparison restricts the translation of these model studies into clinical practice.
Energy potential of a single-fracture, robust, engineered geothermal system
Authors: Danko G. , Jobbik A. , Baracza M. K. , Varga G. , Kovacs I. , Wittig V.
Published: February 2020

Engineered Geothermal Systems (EGS) are promising, but high-risk targets for baseline energy generation. Technology breakthrough is needed to lower the high risks from largely unknown geologic variables and the limited control of the coolant flow field underground. A new, robust EGS (REGS) arrangement and creation technology is reviewed featuring innovative fracture opening, stabilization and permeability control. The geometry, aperture support technique and coolant fluid flow isolation system are all robustly planned and created according the inventive concept. The new elements of the REGS technology are (1) the step-by-step creation, control, and tests of hydraulic fracturing to achieve a planar wing fracture or fractures osculating along the well trajectory; (2) fracture stabilization by hardening grouting injection to create a central support island in each planar wing fracture for zonal isolation; and (3) well-fracture-well fluid circulation for geothermal energy extraction from single, or clustered planar fractures as geothermal heat exchangers. The paper reviews ongoing tests to prove the key components of the REGS geologic heat exchanger with stabilized, large fracture aperture and controlled flow zones for minimized opening pressure loss, seismicity and maximized energy extraction. Flow fields and heat transport are reviewed around zonal isolation of fracture flow by a grouted, blocking island for heat exchange. The robustness is reviewed for the step-by-step construction of a REGS. The paper reports new results from using numerical, coolant flow and heat exchange models to demonstrate the geothermal energy potential of a single REGS well drilled in hot, dry rock.