bluuebunny/crossref_metadata_2025 huggingface dataset:
Mode‐dependent intermediate variable‐based fault estimation for Markovian jump systems with multiple faults
Authors: Kaviarasan Boomipalagan , Kwon Oh‐Min , Jin Park Myeong , Sakthivel Rathinasamy
Published: February 2021

This article investigates the problem of mode‐dependent intermediate variable‐based fault estimation for Markovian jump systems subject to time‐varying delay, exogenous disturbance, process, and sensor faults. The advantages of the proposed design method are: (i) it estimates not only the unknown fault signals, but also the immeasurable states of the system; and (ii) it relaxes the observer matching condition that should be essential for most of the existing fault estimation strategies. In order to facilitate the analysis, the actual system is transformed into an augmented system by including the sensor fault as an auxiliary state. On the basis of which, the intermediate variable and the corresponding observers are established. Following this, two error dynamics are formulated in such a way that a new mode‐ and delay‐dependent boundedness criterion in the probability sense is developed in accordance with the traditional Lyapunov method. Then the theoretical results obtained are validated by using an example based on the F‐404 aircraft engine system. In addition, a comparative study is carried out in the deduced form of the actual system as a special case, where it is shown that the proposed method widens the delay interval compared with some of the recently existing works.
Estimation and modeling of the restricted mean time lost in the presence of competing risks
Authors: Conner Sarah C. , Trinquart Ludovic
Published: February 2021

Survival data with competing or semi‐competing risks are common in observational studies. As an alternative to cause‐specific and subdistribution hazard ratios, the between‐group difference in cause‐specific restricted mean times lost (RMTL) gives the mean difference in life expectancy lost to a specific cause of death or in disease‐free time lost, in the case of a nonfatal outcome, over a prespecified period. To adjust for covariates, we introduce an inverse probability weighted estimator and its variance for the marginal difference in RMTL. We also introduce an inverse probability of censoring weighted regression model for the RMTL. In simulation studies, we examined the finite sample performance of the proposed methods under proportional and nonproportional subdistribution hazards scenarios. We illustrated both methods with competing risks data from the Framingham Heart Study. We estimated sex differences in atrial fibrillation (AF)‐free times lost over 40 years. We also estimated sex differences in mean lifetime lost to cardiovascular disease (CVD) and non‐CVD death over 10 years among individuals with AF.
A novel estimand to adjust for rescue treatment in randomized clinical trials
Authors: Michiels Hege , Sotto Cristina , Vandebosch An , Vansteelandt Stijn
Published: February 2021

The interpretation of randomized clinical trial results is often complicated by intercurrent events. For instance, rescue medication is sometimes given to patients in response to worsening of their disease, either in addition to the randomized treatment or in its place. The use of such medication complicates the interpretation of the intention‐to‐treat analysis. In view of this, we propose a novel estimand defined as the intention‐to‐treat effect that would have been observed, had patients on the active arm been switched to rescue medication if and only if they would have been switched when randomized to control. This enables us to disentangle the treatment effect from the effect of rescue medication on a patient's outcome, while tempering the strong extrapolations that are typically needed when inferring what the intention‐to‐treat effect would have been in the absence of rescue medication. We propose a novel inverse probability weighting method for estimating this effect in settings where the decision to initiate rescue medication is made at one prespecified time point. This estimator relies on specific untestable assumptions, in view of which we propose a sensitivity analysis. We use the method for the analysis of a clinical trial conducted by Janssen Pharmaceuticals, in which patients with type 2 diabetes mellitus can switch to rescue medication for ethical reasons. Monte Carlo simulations confirm that the proposed estimator is unbiased in moderate sample sizes.
Stratified 3D Microtumors as Organotypic Testing Platforms for Screening Pancreatic Cancer Therapies
Authors: Monteiro Maria V. , Gaspar Vítor M. , Mendes Luís , Duarte Iola F. , Mano João F.
Published: February 2021

Cancer‐associated pancreatic stellate cells installed in periacinar/periductal regions are master players in generating the characteristic biophysical shield found in pancreatic ductal adenocarcinoma (PDAC). Recreating this unique PDAC stromal architecture and its desmoplastic microenvironment in vitro is key to discover innovative treatments. However, this still remains highly challenging to realize. Herein, organotypic 3D microtumors that recapitulate PDAC‐stroma spatial bioarchitecture, as well as its biomolecular, metabolic, and desmoplastic signatures, are bioengineered. Such newly engineered platforms, termed stratified microenvironment spheroid models – STAMS – mimic the spatial stratification of cancer‐stromal cells, exhibit a reproducible morphology and sub‐millimeter size. In culture, 3D STAMS secrete the key molecular biomarkers found in human pancreatic cancer, namely TGF‐β, FGF‐2, IL‐1β, and MMP‐9, among others. This is accompanied by an extensive desmoplastic reaction where collagen and glycosaminoglycans (GAGs) de novo deposition is observed. These stratified models also recapitulate the resistance to various chemotherapeutics when compared to standard cancer–stroma random 3D models. Therapeutics resistance is further evidenced upon STAMS inclusion in a tumor extracellular matrix (ECM)‐mimetic hydrogel matrix, reinforcing the importance of mimicking PDAC‐stroma bioarchitectural features in vitro. The 3D STAMS technology represents a next generation of biomimetic testing platforms with improved potential for advancing high‐throughput screening and preclinical validation of innovative pancreatic cancer therapies.
Structural Design for Efficient Perovskite Solar Modules
Authors: Xu Yibo , Wang Shubo , Gu Leilei , Yuan Ningyi , Ding Jianning
Published: February 2021

The fabrication of large area perovskite solar modules (PSMs) is attracting increasing attention. Traditionally, thin film solar modules are prepared by laser‐engraving several isolated lines to create a series of subcells. This process inevitably leads to an increase in series resistance when combining the subcells. Herein, a facile structure combining series and parallel cell connections is designed and developed for constructing PSMs. A champion power conversion efficiency (PCE) of 18.82% is achieved for perovskite composite modules with a designated area of 21.06 cm2. Furthermore, the PSMs can continue to operate even when parts of the device are shaded or broken. Because of the repeated structural arrangement, these modules may be suitable for fabrication on a broader scale for commercial applications.
Transition Metal Exchanged Hydroxyapatite/Fluorapatite Catalysts for C−C and C−N Bond Forming Reactions
Authors: Gadipelly Chandrakanth , Deshmukh Gunjan , Mannepalli Lakshmi Kantam
Published: February 2021

Transition metal (Cu, Zn, Rh, Pd) exchanged hydroxyapatite (HAP)/fluorapatite (FAP) materials have been synthesized by ion‐exchange method resulting in incorporation of the metal ions in the HAP/FAP structure. C−C and C−N bond forming reactions are important in synthetic organic chemistry as these organic transformations are very critical. Transition metal exchanged FAP provides an efficient catalytic system for N‐arylation of haloarenes and Suzuki and Heck coupling of haloarenes. By designing such catalytic materials, our group has developed synthetic methods which allow higher product yields and easy separation with the use of a small amount of catalyst in a shorter reaction time. This account addresses the work carried out in last two decades in the area of C−C and C−N bond forming reactions using transition metal exchanged fluorapatite.
Teaching new tricks to old dogs: A review of drug repositioning of disulfiram for cancer nanomedicine
Authors: Zhao Pengfei , Tang Xueping , Huang Yongzhuo
Published: February 2021

The increasing incidence and mortality of malignant tumors have required the development of diversified innovative therapies. Compared with the new therapeutic molecule invention, it is a more economical and efficient way to reposition old drugs that have been marketed or in clinical trials for tumor treatment. Studies have been carried out for repositioning the old approval drugs that are widely applied clinically with reliable biosafety and effectiveness evidence, including aspirin, artemisinin (and its derivatives, eg, dihydroartemisinin), metformin, and disulfiram (DSF). In addition to the approved pharmacological activity, these old drugs exhibited broad tumor‐suppressive effects. This review summarizes the drug repositioning strategy of DSF through nanotechnology and outlines the DSF nano‐formulations for cancer targeting delivery and therapy.
Combined cancer therapeutics—Tackling the complexity of the tumor microenvironment
Authors: Roma‐Rodrigues Catarina , Raposo Luís R. , Valente Rúben , Fernandes Alexandra R. , Baptista Pedro V.
Published: February 2021

Cancer treatment has yet to find a “silver bullet” capable of selectively and effectively kill tumor cells without damaging healthy cells. Nanomedicine is a promising field that can combine several moieties in one system to produce a multifaceted nanoplatform. The tumor microenvironment (TME) is considered responsible for the ineffectiveness of cancer therapeutics and the difficulty in the translation from the bench to bed side of novel nanomedicines. A promising approach is the use of combinatorial therapies targeting the TME with the use of stimuli‐responsive nanomaterials which would increase tumor targeting. Contemporary combined strategies for TME‐targeting nanoformulations are based on the application of external stimuli therapies, such as photothermy, hyperthermia or ultrasounds, in combination with stimuli‐responsive nanoparticles containing a core, usually composed by metal oxides or graphene, and a biocompatible stimuli‐responsive coating layer that could also contain tumor targeting moieties and a chemotherapeutic agent to enhance the therapeutic efficacy. The obstacles that nanotherapeutics must overcome in the TME to accomplish an effective therapeutic cargo delivery and the proposed strategies for improved nanotherapeutics will be reviewed.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Therapeutic promise of engineered nonsense suppressor tRNAs
Authors: Porter Joseph J. , Heil Christina S. , Lueck John D.
Published: February 2021

Nonsense mutations change an amino acid codon to a premature termination codon (PTC) generally through a single‐nucleotide substitution. The generation of a PTC results in a defective truncated protein and often in severe forms of disease. Because of the exceedingly high prevalence of nonsense‐associated diseases and a unifying mechanism, there has been a concerted effort to identify PTC therapeutics. Most clinical trials for PTC therapeutics have been conducted with small molecules that promote PTC read through and incorporation of a near‐cognate amino acid. However, there is a need for PTC suppression agents that recode PTCs with the correct amino acid while being applicable to PTC mutations in many different genomic landscapes. With these characteristics, a single therapeutic will be able to treat several disease‐causing PTCs. In this review, we will focus on the use of nonsense suppression technologies, in particular, suppressor tRNAs (sup‐tRNAs), as possible therapeutics for correcting PTCs. Sup‐tRNAs have many attractive qualities as possible therapeutic agents although there are knowledge gaps on their function in mammalian cells and technical hurdles that need to be overcome before their promise is realized.

This article is categorized under:

RNA Processing > tRNA Processing

Translation > Translation Regulation
Splicing alterations in healthy aging and disease
Authors: Angarola Brittany Lynn , Anczuków Olga
Published: February 2021

Alternative RNA splicing is a key step in gene expression that allows generation of numerous messenger RNA transcripts encoding proteins of varied functions from the same gene. It is thus a rich source of proteomic and functional diversity. Alterations in alternative RNA splicing are observed both during healthy aging and in a number of human diseases, several of which display premature aging phenotypes or increased incidence with age. Age‐associated splicing alterations include differential splicing of genes associated with hallmarks of aging, as well as changes in the levels of core spliceosomal genes and regulatory splicing factors. Here, we review the current known links between alternative RNA splicing, its regulators, healthy biological aging, and diseases associated with aging or aging‐like phenotypes.

This article is categorized under:

RNA in Disease and Development > RNA in Disease

RNA Processing > Splicing Regulation/Alternative Splicing
Riemann-DTI Geodesic Tractography Revisited
Authors: Florack Luc , Sengers Rick , Meesters Stephan , Smolders Lars , Fuster Andrea
Published: February 2021

Clinical tractography is a challenging problem in diffusion tensor imaging (DTI) due to persistent validation issues. Geodesic tractography, based on a shortest path principle, is conceptually appealing, but has not produced convincing results so far. A major weakness is its rigidity with respect to candidate tracts it is capable of producing given a pair of endpoints, showing a tendency to produce false positives (such as shortcuts) and false negatives (e.g. if a shortcut supplants the correct solution). We propose a new geodesic paradigm that appears to overcome these problems, making a step towards semi-automatic clinical use. To this end we couple the DTI tensor field to afamilyof Riemannian metrics, governed by control parameters. In practice these parameters may allow for edits by an expert through manual selection among multiple tract suggestions, or for bringing in a priori knowledge. In this paper, however, we consider an automatic, evidence-driven procedure to determine optimal controls and corresponding tentative tracts, and illustrate the role of edits to remediate erroneous defaults.
Integration und Öffentliche Mobilität: Die Rolle der Planung
Authors: Schwedes Oliver
Published: February 2021

Nachdem der öffentliche Verkehr in den ersten Nachkriegsjahrzehnten im Zuge der wirtschaftlichen Prosperität stetig an Bedeutung zugunsten des privaten Autoverkehrs verloren hatte, wurde er in den 1970er Jahren wiederentdeckt. Allerdings war das wiedererwachte Interesse der Verkehrsplaner*innen am öffentlichen Verkehr mehrheitlich dadurch motiviert, den rasant wachsenden Autoverkehr zu entlasten, um die Stauanfälligkeit zu reduzieren und damit die ‚freie Fahrt für freie Bürger‘ zu gewährleisten. Damals etabliert sich der verkehrspolitische Konsens, dass der öffentliche Verkehr auch zukünftig als Teil der Daseinsvorsorge, ein Mindestmaß an Mobilität für diejenigen erbringen soll, die sich kein Auto leisten können.
Teilhabe und Öffentliche Mobilität: Die Rolle der Politik
Authors: Daubitz Stephan
Published: February 2021

Waren Verkehrspolitik und -planung in der Vergangenheit zumeist beschränkt auf die Verringerung von Raumwiderständen zur Herstellung von reibungslosen automobilen ‚Verkehrsflüssen‘, hat sich durch die Einbeziehung von Gerechtigkeitskonzeptionen und die präzise Unterscheidung zwischen den Begriffen Verkehr und Mobilität sowie den Einbezug des Individuums mit seinen subjektiven Wahrnehmungen die Möglichkeit eröffnet, eine innovative Form von Verkehrsplanung bzw. Mobilitätspolitik zu gestalten.
Öffentliche Mobilität und neue Formen der Governance: das Beispiel Volksentscheid Fahrrad
Authors: von Schneidemesser Dirk
Published: February 2021

Der Anstoß für Deutschlands erstes Fahrradgesetz kam aus der Zivilgesellschaft. Der Impuls entstand aus dem weiterhin ungeklärten Konflikt zwischen der Autofixierung der konservativen deutschen Verkehrspolitik und dem progressiven Wunsch nach einer nachhaltigen Mobilität, die sich an den Bedürfnissen der Bürger*innen orientieren soll und eine Umverteilung des Straßenraumes zugunsten des Radverkehrs erforderte. Dass Verkehr nachhaltiger gestaltet werden muss, war Konsens. Über das Wie gingen die Meinungen stark auseinander.
BPS invariants for 3-manifolds at rational level K
Authors: Chung Hee-Joong
Published: February 2021

Abstract

We consider the Witten-Reshetikhin-Turaev invariants or Chern-Simons partition functions at or around roots of unity $$ q={e}^{\frac{2\pi i}{K}} $$
q
=

e

2
πi

K

with a rational level K = $$ \frac{r}{s} $$

r
s

where r and s are coprime integers. From the exact expression for the G = SU(2) Witten-Reshetikhin-Turaev invariants of the Seifert manifolds at a rational level obtained by Lawrence and Rozansky, we provide an expected form of the structure of the Witten-Reshetikhin-Turaev invariants in terms of the homological blocks at a rational level. Also, we discuss the asymptotic expansion of knot invariants around roots of unity where we take a limit different from the limit in the standard volume conjecture.
Opacity from Loops in AdS
Authors: Costantino Alexandria , Fichet Sylvain
Published: February 2021

Abstract

We investigate how quantum dynamics affects the propagation of a scalar field in Lorentzian AdS. We work in momentum space, in which the propagator admits two spectral representations (denoted “conformal” and “momentum”) in addition to a closed-form one, and all have a simple split structure. Focusing on scalar bubbles, we compute the imaginary part of the self-energy ImΠ in the three representations, which involves the evaluation of seemingly very different objects. We explicitly prove their equivalence in any dimension, and derive some elementary and asymptotic properties of ImΠ.

Using a WKB-like approach in the timelike region, we evaluate the propagator dressed with the imaginary part of the self-energy. We find that the dressing from loops exponentially dampens the propagator when one of the endpoints is in the IR region, rendering this region opaque to propagation. This suppression may have implications for field-theoretical model-building in AdS. We argue that in the effective theory (EFT) paradigm, opacity of the IR region induced by higher dimensional operators censors the region of EFT breakdown. This confirms earlier expectations from the literature. Specializing to AdS5, we determine a universal contribution to opacity from gravity.
Non-relativistic three-dimensional supergravity theories and semigroup expansion method
Authors: Concha Patrick , Ipinza Marcelo , Ravera Lucrezia , Rodríguez Evelyn
Published: February 2021

Abstract

In this work we present an alternative method to construct diverse non-relativistic Chern-Simons supergravity theories in three spacetime dimensions. To this end, we apply the Lie algebra expansion method based on semigroups to a supersymmetric extension of the Nappi-Witten algebra. Two different families of non-relativistic superalgebras are obtained, corresponding to generalizations of the extended Bargmann superalgebra and extended Newton-Hooke superalgebra, respectively. The expansion method considered here allows to obtain known and new non-relativistic supergravity models in a systematic way. In particular, it immediately provides an invariant tensor for the expanded superalgebra, which is essential to construct the corresponding Chern-Simons supergravity action. We show that the extended Bargmann supergravity and its Maxwellian generalization appear as particular subcases of a generalized extended Bargmann supergravity theory. In addition, we demonstrate that the generalized extended Bargmann and generalized extended Newton-Hooke supergravity families are related through a contraction process.
Delinquentes Verhalten im Rahmen frontotemporaler Demenzen und der Alzheimer-Erkrankung
Authors: Haußmann R. , Krug C. , Noppes F. , Brandt M. , Lange J. , Donix M.
Published: February 2021

Seniorenkriminalität ist insgesamt ein seltenes Phänomen. Bei älteren Straftätern hat es die Justiz in hohem Maß mit Ersttätern zu tun, die mehrheitlich männlichen Geschlechts sind. Eine mögliche Ursache von Erstkriminalität im höheren Lebensalter stellen Demenzerkrankungen dar. Es ist jedoch wenig dazu bekannt, wie häufig Demenzerkrankungen tatsächlich Ursache delinquenten Verhaltens im höheren Lebensalter sind. Die Demenzprävalenz in Studien mit forensischen Kohorten älterer Straftäter ist sehr heterogen, was vor allem studienmethodisch begründet ist. Längsschnittlich begehen etwa 50 % aller Patienten mit frontotemporaler Demenz und etwa 10 % aller Patienten mit Alzheimer-Demenz Delikte im Erkrankungsverlauf. Die neurobiologischen Entstehungsmechanismen von Delinquenzverhalten im Rahmen von Demenzen sind unvollständig verstanden. Nach aktuellen Erkenntnissen wird davon ausgegangen, dass Erstdelinquenz im Rahmen von Demenzerkrankungen als Folge von Beeinträchtigungen der sozialen Kognition, Empathiefähigkeit und der Verhaltenskontrolle zu verstehen ist. Bedeutsam sind insbesondere frontale und anteriore temporale Hirnstrukturen. Demenzerkrankungen können zu Beeinträchtigungen der Schuldfähigkeit führen, weshalb forensisch-psychiatrische Sachverständige auch mit Demenzerkranken konfrontiert sind. Hierbei müssen ätiologiespezifische Besonderheiten berücksichtigt werden. Insbesondere Erstdelikte im Rahmen wesensuntypischer Persönlichkeitsänderungen nach dem 50. Lebensjahr sollten an eine neurodegenerative Ätiologie denken lassen. Insbesondere frontotemporale Demenzerkrankungen, wie die behaviorale Variante einer frontotemporalen Demenz (bvFTD), aber auch die semantische Demenz (svPPA), prädisponieren zu delinquentem Verhalten.Diese Arbeit fasst aktuelle Erkenntnisse zu dieser forensisch-psychiatrisch, aber auch klinisch relevanten Thematik zusammen.
More than additive effects on liver triglyceride accumulation by combinations of steatotic and non-steatotic pesticides in HepaRG cells
Authors: Lasch Alexandra , Marx-Stoelting Philip , Braeuning Albert , Lichtenstein Dajana
Published: February 2021

The liver is constantly exposed to mixtures of hepatotoxic compounds, such as food contaminants and pesticides. Dose addition is regularly assumed for mixtures in risk assessment, which however might not be sufficiently protective in case of synergistic effects. Especially the prediction of combination effects of substances which do not share a common adverse outcome (AO) might be problematic. In this study, the focus was on the endpoint liver triglyceride accumulation in vitro, an indicator of hepatic fatty acid changes. The hepatotoxic compounds difenoconazole, propiconazole and tebuconazole were chosen which cause hepatic fatty acid changes in vivo, whereas fludioxonil was chosen as a hepatotoxic substance not causing fatty acid changes. Triglyceride accumulation was analyzed for combinations of steatotic and non-steatotic pesticides in human HepaRG hepatocarcinoma cells. Investigations revealed a potentiation of triglyceride accumulation by mixtures of the steatotic compounds with the non-steatotic fludioxonil, as compared to the single compounds. Mathematical modeling of combination effects indicated more than additive effects for the tested combinations if the method by Chou was applied, and a decrease in EC50 values of the steatotic compounds when applied in mixtures. Use of an adverse outcome pathway (AOP)-driven testing strategy for liver steatosis showed interactions of the test compounds with the nuclear receptors AHR, CAR and PXR, as well as a downregulation of ACOX2. An ACOX2-dependent mechanism underlying the observed mixture effect could not be verified using a siRNA approach. By contrast, a toxicokinetic interaction was identified including an inhibition of the metabolic enzyme CYP3A4 by fludioxonil and a decreased metabolic conversion of the CYP3A4 substrate difenoconazole when used in mixture experiments. In conclusion, an interaction by a steatotic and a non-steatotic compound at the toxicokinetic level on the endpoint triglyceride accumulation in vitro was described.
Free Boundary Regularity for Almost Every Solution to the Signorini Problem
Authors: Fernández-Real Xavier , Ros-Oton Xavier
Published: February 2021

We investigate the regularity of the free boundary for the Signorini problem in $${\mathbb {R}}^{n+1}$$

R

n
+
1

. It is known that regular points are $$(n-1)$$

(
n
-
1
)

-dimensional and $$C^\infty $$

C
∞

. However, even for $$C^\infty $$

C
∞

obstacles $$\varphi $$
φ
, the set of non-regular (or degenerate) points could be very large—e.g. with infinite $${\mathcal {H}}^{n-1}$$

H

n
-
1

measure. The only two assumptions under which a nice structure result for degenerate points has been established are when $$\varphi $$
φ
is analytic, and when $$\Delta \varphi < 0$$

Δ
φ
<
0

. However, even in these cases, the set of degenerate points is in general $$(n-1)$$

(
n
-
1
)

-dimensional—as large as the set of regular points. In this work, we show for the first time that, “usually”, the set of degenerate points is small. Namely, we prove that, given any $$C^\infty $$

C
∞

obstacle, for almost every solution the non-regular part of the free boundary is at most $$(n-2)$$

(
n
-
2
)

-dimensional. This is the first result in this direction for the Signorini problem. Furthermore, we prove analogous results for the obstacle problem for the fractional Laplacian $$(-\Delta )^s$$

(
-
Δ
)

s

, and for the parabolic Signorini problem. In the parabolic Signorini problem, our main result establishes that the non-regular part of the free boundary is $$(n-1-\alpha _\circ )$$

(
n
-
1
-

α
∘

)

-dimensional for almost all times t, for some $$\alpha _\circ > 0$$

α
∘

>
0

. Finally, we construct some new examples of free boundaries with degenerate points.
Adverse events related to total ankle replacement devices: an analysis of reports to the United States Food and Drug Administration
Authors: Mahmoud Karim , Metikala Sreenivasulu , O’Connor Kathryn M. , Farber Daniel C.
Published: February 2021

Background

The published outcomes of total ankle replacement (TAR) implants came from limited institutions creating observational bias. For broader perspective, we queried the Food and Drug Administration’s (FDA) Manufacturer and User Facility Device Experience (MAUDE) voluntary database to explore complications reported outside published literature.

Methods

The database was reviewed retrospectively between November 2011 and April 2019 using two product codes assigned to six TAR devices.

Results

Among 648 relevant reports available in the database, common complications were aseptic loosening (19.3%), infection (18.2%), and alignment/mechanical issues (16.5%). Others included instrument/instrumentation complications, impingement, polyethylene problems, fractures, avascular necrosis of talus (AVN), and packaging issues.

Conclusion

MAUDE database revealed various patterns of device-related malfunctions that have been under-reported in published data. Despite inconsistency in the available reports, it provided opportunities for improvements in quality control, device design, and ultimately patient safety. Database would be further strengthened by more robust reporting mechanism or mandatory reporting of device-related complications.
Small one-dimensional Euclidean preference profiles
Authors: Chen Jiehua , Grottke Sven
Published: February 2021

We characterize one-dimensional Euclidean preference profiles with a small number of alternatives and voters. We show that every single-peaked preference profile withtwovoters is one-dimensional Euclidean, and that every preference profile with up to five alternatives is one-dimensional Euclidean if and only if it is both single-peaked and single-crossing. By the work of Chen et al.  (Social Choice and Welfare 48(2):409–432, 2017), we thus obtain that the smallest single-peaked and single-crossing preference profiles that arenotone-dimensional Euclidean consist of three voters and six alternatives.
Risikoidentifikation bei Polypharmazie in einer Pflegeheimpopulation
Authors: Specka Michael , Groll Maria , Scherbaum Norbert , Wiltfang Jens , Benninghoff Jens
Published: February 2021

Einleitung

Multimorbidität im Alter ist u. a. ein Grund für intensivierte Pharmakotherapie. Gleichzeitig kann es mit steigender Medikamentenzahl zu einer Zunahme der Multimorbidität kommen, insbesondere wenn Interaktionen zwischen den Wirkstoffen zu unerwünschten Arzneiwirkungen (UAW) führen. Ziel dieser Untersuchung war es, in einer Pilotstudie Patienten zu identifizieren, die einem erhöhten Risiko für UAW unterliegen.

Methoden

In einer Querschnittserhebung wurden 918 in Heimen lebende psychiatrisch behandelte Alterspatienten untersucht (Altersmittel: 79,3 (±11,6) Jahre; 31,8 % Männer). Es kamen exemplarisch verschiedene Methoden zur Identifikation von möglichen Risikopatienten zur Anwendung: eine die Interaktionen der Gesamtmedikation erfassende „Clinical-Decision-Support-Software“(CDSS)-Onlinedatenbank, mediQ, und eine Negativliste, die pauschal zu vermeidende Präparate indiziert, die PRISCUS-Liste.

Ergebnis

Es hatten 76,3 % aller Studienpatienten bei Betrachtung der Gesamtmedikation ein klinisch relevantes Interaktionsrisiko (IR), 2,2 % standen unter einem darüber hinausgehenden potenziell starken UAW-Risiko durch Interaktionen. Ungefähr ein Viertel der untersuchten Studienpopulation erhielt potenziell inadäquate Medikamente gemäß PRISCUS.

Schlussfolgerung

Diese unterschiedlichen Zahlen zeigen die Komplexität der eindeutigen Identifikation von Risikopatienten am Beispiel dieser beiden, auf unterschiedlicher Grundlage basierenden Instrumente. Trotz des technischen Fortschritts sollte der Schwerpunkt der UAW-Vermeidung unverändert darauf liegen, Medikamente erst nach besonders gründlicher Prüfung der klinischen Indikation zu verordnen und eine adäquate Verlaufskontrolle zu gewährleisten. Die neuen CDSS oder Negativlisten bieten hierbei Unterstützung.
A sprayable Acid-Oxidizing solution containing hypochlorous acid (AOS2020) efficiently and safely inactivates SARS-Cov-2: a new potential solution for upper respiratory tract hygiene
Authors: Giarratana Nadia , Rajan Balan , Kamala Kannan , Mendenhall Michelle , Reiner Giorgio
Published: February 2021

Introduction

To eliminate the COVID-19 pandemic, the transmission of the virus SARS-CoV-2 among the population needs to be blocked and/or at least reduced. Upper respiratory tract viral loads are highest in the early stages of the disease, and high loads are associated with higher mortality rates. This study aims to evaluate the virucidal efficacy of AOS2020, a novel sprayable Acid-Oxidizing solution containing pure and stable hypochlorous acid (HClO), on human coronavirus SARS-Cov-2 in vitro, and the tolerability profile on nasal and oral mucosa suggesting to be a potential solution for upper respiratory hygiene.

Method

Virucidal assays and intranasal and oral irritation tests were undertaken in accordance with relevant national and international guidance and methods.

Results

In pre-clinical tests, the AOS2020, showed > 99.8% virucidal efficacy in < 1 min against SARS-Cov-2. The safety profile testing on both the nasal and oral mucosa indicates that AOS2020 is non-irritant.

Conclusion

These initial results indicate that this product has the potential treatment to reduce viral load in the upper respiratory tract.
Large deformation behavior of functionally graded porous curved beams in thermal environment
Authors: Nikrad S. F. , Kanellopoulos A. , Bodaghi M. , Chen Z. T. , Pourasghar A.
Published: February 2021

The in-plane thermoelastic response of curved beams made of porous materials with different types of functionally graded (FG) porosity is studied in this research contribution. Nonlinear governing equations are derived based on the first-order shear deformation theory along with the nonlinear Green strains. The nonlinear governing equations are solved by the aid of the Rayleigh–Ritz method along with the Newton–Raphson method. The modified rule-of-mixture is employed to derive the material properties of imperfect FG porous curved beams. Comprehensive parametric studies are conducted to explore the effects of volume fraction and various dispersion patterns of porosities, temperature field, and arch geometry as well as boundary conditions on the nonlinear equilibrium path and stability behavior of the FG porous curved beams. Results reveal that dispersion and volume fraction of porosities have a significant effect on the thermal stability path, maximum stress, and bending moment at the crown of the curved beams. Moreover, the influence of porosity dispersion and structural geometry on the central radial and in-plane displacement of the curved beams is evaluated. Results show that various boundary conditions make a considerable difference in the central radial displacements of the curved beams with the same porosity dispersion. Due to the absence of similar results in the specialized literature, this paper is likely to provide pertinent results that are instrumental toward a reliable design of FG porous curved beams in thermal environment.
Modeling inter-trial variability of pointing movements during visuomotor adaptation
Authors: Eggert Thomas , Henriques Denise Y. P. , ’t Hart Bernard M. , Straube Andreas
Published: February 2021

Trial-to-trial variability during visuomotor adaptation is usually explained as the result of two different sources, planning noise and execution noise. The estimation of the underlying variance parameters from observations involving varying feedback conditions cannot be achieved by standard techniques (Kalman filter) because they do not account for recursive noise propagation in a closed-loop system. We therefore developed a method to compute the exact likelihood of the output of a time-discrete and linear adaptation system as has been used to model visuomotor adaptation (Smith et al. in PLoS Biol 4(6):e179, 2006), observed under closed-loop and error-clamp conditions. We identified the variance parameters by maximizing this likelihood and compared the model prediction of the time course of variance and autocovariance with empiric data. The observed increase in variability during the early training phase could not be explained by planning noise and execution noise with constant variances. Extending the model by signal-dependent components of either execution noise or planning noise showed that the observed temporal changes of the trial-to-trial variability can be modeled by signal-dependent planning noise rather than signal-dependent execution noise. Comparing the variance time course between different training schedules showed that the signal-dependent increase of planning variance was specific for the fast adapting mechanism, whereas the assumption of constant planning variance was sufficient for the slow adapting mechanisms.
Effects of repeated testing in a pen-and-paper test of selective attention (FAIR-2)
Authors: Wühr Bianca , Wühr Peter
Published: February 2021

The FAIR-2 (‘Frankfurter Aufmerksamkeitsinventar’) is a pen-and-paper test of visual attention in which participants have to search for targets among distractors. For similar pen-and-paper tests of attention (e.g., d2), the repetition of the test causes large improvements in performance that threaten both its (retest) reliability and validity. We investigated the size and possible sources of practice effects in the FAIR-2 in three experiments. In Experiments 1 and 2, participants were tested twice using the original FAIR-2. We compared how performance changed after 2 weeks (Experiment 1) or 3 months (Experiment 2), when the test was repeated (complete repetition), or when targets and distractors changed their roles (test reversal). For Experiment 3, we used self-constructed versions of the FAIR that allowed for a third neutral condition (complete alternation) without any stimulus overlap between the two tests. The complete repetition condition produced strong performance gains (25–35%) that persisted for 3 months. For the complete-alternation condition, we observed small to moderate improvements, suggesting that stimulus-independent learning had occurred in session 1. Finally, performance did not differ between test reversal and complete alternation, therefore, suggesting that improvements in target processing had caused the large improvements in the complete-repetition condition.
Efficient local locking for massively multithreaded in-memory hash-based operators
Authors: Romanous Bashar , Windh Skyler , Absalyamov Ildar , Budhkar Prerna , Halstead Robert , Najjar Walid , Tsotras Vassilis
Published: February 2021

The join and group-by aggregation are two memory intensive operators that are affecting the performance of relational databases. Hashing is a common approach used to implement both operators. Recent paradigm shifts in multi-core processor architectures have reinvigorated research into how the join and group-by aggregation operators can leverage these advances. However, the poor spatial locality of the hashing approach has hindered performance on multi-core processor architectures which rely on using large cache hierarchies for latency mitigation. Multithreaded architectures can better cope with poor spatial locality by masking memory latency with many outstanding requests. Nevertheless, the number of parallel threads, even in the most advanced multithreaded processors, such as UltraSPARC, is not enough to fully cover the main memory access latency. In this paper, we explore the hardware re-configurability of FPGAs to enable deeper execution pipelines that maintain hundreds (instead of tens) of outstanding memory requests across four FPGAs-drastically increasing concurrency and throughput. We present two end-to-end in-memory accelerators for the join and group-by aggregation operators using FPGAs. Both accelerators use massive multithreading to mask long memory delays of traversing linked-list data structures, while concurrently managing hundreds of thread states across four FPGAs locally. We explore how content addressable memories can be intermixed within our multithreaded designs to act as a synchronizing cache, which enforces locks and merges jobs together before they are written to memory. Throughput results for our hash-join operator accelerator show a speedup between 2$$\times $$
×
and 3.4$$\times $$
×
over the best multi-core approaches with comparable memory bandwidths on uniform and skewed datasets. The accelerator for the hash-based group-by aggregation operator demonstrates that leveraging CAMs achieves average speedup of 3.3$$\times $$
×
with a best case of 9.4$$\times $$
×
in terms of throughput over CPU implementations across five types of data distributions.
Outbreak of Central American born Shigella sonnei in two youth camps in Belgium in the summer of 2019
Authors: Van den Bossche An , Ceyssens Pieter-Jan , Denayer Sarah , Hammami Naïma , van den Beld Maaike , Dallman Timothy J. , Mattheus Wesley
Published: February 2021

In 2019, an outbreak of Shigella sonnei occurred during two youth camps in Belgium. The clustering of isolates from both camps was confirmed by next-generation sequencing, as well as a secondary infection of a technician. The outbreak strain clustered with internationally isolated strains from patients with recent travel history to Central America. This report exemplifies enhanced surveillance and international collaboration between public health institutes by enabling to link local outbreaks to region-specific sublineages circulating abroad.
A conformal Yamabe problem with potential on the Euclidean space
Authors: Catino Giovanni , Gazzola Filippo , Mastrolia Paolo
Published: February 2021

We consider, in the Euclidean setting, a conformal Yamabe-type equation related to a potential generalization of the classical constant scalar curvature problem and which naturally arises in the study of Ricci solitons structures. We prove existence and nonexistence results, focusing on the radial case, under some general hypothesis on the potential.
Single-molecule observation of diffusion and catalysis in nanoporous solids
Authors: Maris J. J. Erik , Fu Donglong , Meirer Florian , Weckhuysen Bert M.
Published: February 2021

Nanoporous solids, including microporous, mesoporous and hierarchically structured porous materials, are of scientific and technological interest because of their high surface-to-volume ratio and ability to impose shape- and size-selectivity on molecules diffusing through them. Enormous efforts have been put in the mechanistic understanding of diffusion–reaction relationships of nanoporous solids, with the ultimate goal of developing materials with improved catalytic performance. Single-molecule localization microscopy can be used to explore the pore space via the trajectories of individual molecules. This ensemble-free perspective directly reveals heterogeneities in diffusion and diffusion-related reactivity of individual molecules, which would have been obscured in bulk measurements. In this article, we review developments in the spatial and temporal characterization of nanoporous solids using single-molecule localization microscopy. We illustrate various aspects of this approach, and showcase how it can be used to follow molecular diffusion and reaction behaviors in nanoporous solids.
Inventory decision in a periodic review inventory model with two complementary products
Authors: Poormoaied Saeed
Published: February 2021

Interaction effect across complementary products plays an important role in characterizing the optimal inventory policy. The inventory levels of complementary products are interrelated due to interaction between demand streams. In this paper, we consider a periodic review base-stock policy in the presence of two complementary products with interrelated demands and joint replenishment. Demands are modeled by a Poisson process and any unmet demand is lost. Demands can be in sets of one unit of each or jointly. If an arrival demand requests two products jointly and one of the products is not in stock, then the whole demand is lost. We aim to investigate how this interrelated demand phenomenon influences the optimal base-stock levels and the period length of a periodic review policy. We utilize the renewal reward theorem to derive the explicit expression of the expected profit rate in the system. The goal is to determine the optimal period length and the base-stock levels such that the expected profit rate is maximized. Enumeration and approximation algorithms are employed to find the optimal and near-optimal solutions, respectively. The approximation algorithm is based on a scenario with independent demand processes which results in an explicit expression for the long-run profit per time unit and leads to analytical solutions for optimal policies. Our numerical results reveal that the solutions obtained by the approximation algorithm are close to optimal solutions. Numerical experiences show that the maximum profit in the system is achieved if the proportion of customers with jointly demand increases. Moreover, the interaction effect between demand processes has a significant impact on the control policy performance when the units lost sales and unit holding costs are high, and the demand rare is low.
Evolutionary biology meets consciousness: essay review of Simona Ginsburg and Eva Jablonka’s The Evolution of the Sensitive Soul
Authors: Browning Heather , Veit Walter
Published: February 2021

In this essay, we discuss Simona Ginsburg and Eva Jablonka’s The Evolution of the Sensitive Soul from an interdisciplinary perspective. Constituting perhaps the longest treatise on the evolution of consciousness, Ginsburg and Jablonka unite their expertise in neuroscience and biology to develop a beautifully Darwinian account of the dawning of subjective experience. Though it would be impossible to cover all its content in a short book review, here we provide a critical evaluation of their two key ideas—the role of Unlimited Associative Learning in the evolution of, and detection of, consciousness and a metaphysical claim about consciousness as a mode of being—in a manner that will hopefully overcome some of the initial resistance of potential readers to tackle a book of this length.
Analysis of the Influence of the Length Scales in a Boundary-Layer Model
Authors: Ferrero Enrico , Canonico Massimo
Published: February 2021

We consider the Janjic (NCEP Office Note 437:61, 2001) boundary-layer model, which is one of the most widely used in numerical weather prediction models. This boundary-layer model is based on a number of length scales that are, in turn, obtained from a master length multiplied by constants. We analyze the simulation results obtained using different sets of constants with respect to measurements using sonic anemometers, and interpret these results in terms of the turbulence processes in the atmosphere and of the role played by the different length scales. The simulations are run on a virtual machine on the Chameleon cloud for low-wind-speed, unstable, and stable conditions.
Public preferences for heritage conservation strategies: a choice modelling approach
Authors: Throsby David , Zednik Anita , Araña Jorge E.
Published: February 2021

Studies aiming at valuing cultural and natural heritage projects are often focussed on one or only a few sites, whereas planning decisions concerning the allocation of public funds to heritage conservation deal with classes of heritage rather than single sites. In addition, such planning decisions are almost always concerned with non-monetary values that need to be incorporated into assessment procedures if the total value of alternative strategies is to be estimated. In this paper, we put forward and estimate models to address both of these issues within a choice-modelling framework. The method is developed in the context of conservation of a particular class of cultural heritage, namely major historic buildings in a city or country. We report results from a discrete choice experiment to assess public preferences in which the choices are alternative conservation programs and the attributes are dimensions of the programs’ cultural and economic value. The model is estimated from survey data using several flexible econometric specifications. We show that the methods developed can be used to obtain robust estimates of the economic value of this category of buildings. We also find a significant contribution of all aspects of cultural value to the formation of conservation preferences and the public’s willingness to pay.