bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired regenerative capacity and senescence‐associated secretory phenotype in mesenchymal stromal cells from samples of patients with aseptic joint arthroplasty loosening
Authors: Ebert Regina , Weissenberger Manuel , Braun Clemens , Wagenbrenner Mike , Herrmann Marietta , Müller‐Deubert Sigrid , Krug Melanie , Jakob Franz , Rudert Maximilian
Published: March 2021

Aseptic loosening of total hip and knee joint replacements is the most common indication for revision surgery after primary hip and knee arthroplasty. Research suggests that exposure and uptake of wear by mesenchymal stromal cells (MSC) and macrophages results in the secretion of proinflammatory cytokines and local osteolysis, but also impaired cell viability and regenerative capacity of MSC. Therefore, this in vitro study compared the regenerative and differentiation capacity of MSC derived from patients undergoing primary total hip arthroplasty (MSCprim) to MSC derived from patients undergoing revision surgery after aseptic loosening of total hip and knee joint implants (MSCrev). Regenerative capacity was examined by measuring the cumulative population doubling (CPD) in addition to the number of passages until cells stopped proliferating. Osteogenesis and adipogenesis in monolayer cultures were assessed using histological stainings. Furthermore, RT‐PCR was performed to evaluate the relative expression of osteogenic and adipogenic marker genes as well as the expression of markers for a senescence‐associated secretory phenotype (SASP). MSCrev possessed a limited regenerative capacity in comparison to MSCprim. Interestingly, MSCrev also showed an impaired osteogenic and adipogenic differentiation capacity compared to MSCprim and displayed a SASP early after isolation. Whether this is the cause or the consequence of the aseptic loosening of total joint implants remains unclear. Future research should focus on the identification of specific cell markers on MSCprim, which may influence complication rates such as aseptic loosening of total joint arthroplasty to further individualize and optimize total joint arthroplasty.
Sustained reduction in discharge opioid volumes through provider education: Results of 1168 cancer surgery patients over 2 years
Authors: Kim Bradford J. , Newhook Timothy E. , Blumenthaler Alisa , Chiang Yi‐Ju , Aloia Thomas A. , Roland Christina L. , Katz Matthew H. G. , Vauthey Jean‐Nicolas , Lee Jeffrey E. , Tzeng Ching‐Wei D.
Published: March 2021

Background

An opioid reduction education program to decrease discharge opioid prescriptions was initiated in our Department of Surgical Oncology. The study's aim was to measure the results and sustainability of these interventions 1 year later.

Methods

This prospective quality improvement project identified patients undergoing resection in five index tumor sites (peritoneal surface, sarcoma, stomach, pancreas, liver) at a high‐volume cancer center. Patients were grouped into pre‐education (PRE: July 2017–July 2018) and posteducation (POST: September 2018–July 2019) periods, before and after departmental education talks and videos in August 2018. Opioids were converted to oral morphine equivalents (OME) to compare the groups.

Results

Of 1168 evaluable patients (PRE 646, 55%; POST 522, 45%), the median last‐24‐h inpatient OME was 15 mg in PRE patients and 10 mg in POST patients (p < .001). Median discharge OME decreased from 200 mg in PRE to 100 mg in POST patients (p < .001). The frequency of patients with zero discharge opioids increased from 11% to 19% (p < .001). This discharge OME reduction amounted to 52,200 mg OME saved, or the equivalent of 6960 5‐mg oxycodone pills not disseminated.

Conclusions

A perioperative opioid reduction education program targeted to providers halved discharge OME, with sustained reductions 1 year later.
Saving money or losing face? An international study on social stigmatization in discount stores
Authors: Homburg Christian , Ukrainets Kateryna
Published: March 2021

Social stigmatization is detrimental to its victims, leaving them devalued and discriminated against by society. Can social stigmatization of marginalized low‐income social groups also influence non‐stigmatized high‐status consumers? If so, does the individual's cultural value of power distance (PD) moderate this relationship? Previous consumer research on social stigmatization has neglected these questions. In a discount‐store context, we analyze the moderating effect of an individual's cultural value of PD on the link between the social stigmatization of low‐income customers and the customer loyalty of higher‐income customers. In an international scenario‐based experimental study, we collected data in the United Kingdom, Germany, China, and Russia, resulting in a sample size of 1675 consumers. The empirical findings, which are based on structural equation modeling with latent variables, show the positive direct and negative indirect relationship between the social stigmatization of low‐income customers and the customer loyalty of higher‐income customers. The results of a multi‐group causal analysis indicate that an individual's cultural value of PD strongly influences the strength of this relationship. These findings demonstrate that social stigmatization has stronger effects on individuals with a high level of PD.
Impact of alliances and delay rate on airline performance
Authors: Li Ying , Lin Tai‐Yu , Chiu Yung‐ho , Lin Shu‐Ning , Chang Tzu‐Han
Published: March 2021

To examine the operational aviation efficiencies in 22 Asian airlines, the airlines were classified into three strategic alliances, and their respective efficiencies assessed using a modified dynamic undesirable meta‐frontier data envelopment analysis model. It was found that (1) average aviation industry efficiency declined from 2014 to 2016; (2) the number of airport input variables and the output delay rate factor were important inefficiency indicators; and (3) only the One World strategic alliance had an increasing technology gap ratio, which indicated that aviation efficiency was continuing to improve.
Existence and stability for a nonlinear hybrid differential equation of fractional order via regular Mittag–Leffler kernel
Authors: Slimane Ibrahim , Dahmani Zoubir , Nieto Juan J. , Abdeljawad Thabet
Published: March 2021

This paper deals with a nonlinear hybrid differential equation written using a fractional derivative with a Mittag–Leffler kernel. Firstly, we establish the existence of solutions to the studied problem by using the Banach contraction theorem. Then, by means of the Dhage fixed‐point principle, we discuss the existence of mild solutions. Finally, we study the Ulam–Hyers stability of the introduced fractional hybrid problem.
Dispersion of mean consecutive differences in single‐fiber electromyography increases diagnostic sensitivity for myasthenia gravis
Authors: Kojima Yuta , Shibuya Kazumoto , Uzawa Akiyuki , Kano Hiroki , Nakamura Keigo , Yasuda Manato , Suzuki Yo‐ichi , Tsuneyama Atsuko , Suichi Tomoki , Ozawa Yukiko , Misawa Sonoko , Noto Yu‐ichi , Mizuno Toshiki , Kuwabara Satoshi
Published: March 2021

Introduction

In this study we aimed to investigate the dispersion of mean consecutive difference (MCD) of concentric needle jitter studies of patients with myasthenia gravis (MG) and its effect on diagnostic sensitivity for MG.

Methods

One hundred fifty‐three patients, including 76 patients with MG and 77 controls with possible MG who later received another diagnosis, underwent stimulated concentric needle jitter studies of the frontalis muscle. MCD mean, standard deviation (SD), and coefficient of variation (CV) were calculated. Diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) analyses.

Results

MG patients showed a significantly greater MCD mean (MG: control, 26.3 μs; 13.5 μs [median]; P < .0001), MCD SD (MG: control, 12.8 μs; 5.1 μs [median]; P < .0001), and MCD CV (MG: control, 46.1; 37.5 [median]; P < .001) than those without MG. An ROC curve of SD showed a large area under the curve (0.88), and a cut‐off value of 7.2 μs, which was calculated by maximum Youden index, exhibited high diagnostic sensitivity (86%) for MG. Combined MCD mean, outliers, and SD criteria showed higher sensitivity (88%) than conventional criteria alone (82%), at the expense of lower specificity. Five MG patients with normal MCD mean and abnormal MCD SD had only ocular symptoms.

Discussion

The dispersion of MCD as measured by MCD SD greater than 7.2 μs is significantly increased in patients with MG and may be a useful measure of abnormal jitter in the diagnosis of MG, especially for identifying patients with mild disease.
Fabrication and performance evaluation of waste cotton and polyester fiber‐reinforced green composites for building and construction applications
Authors: Kamble Zunjarrao , Behera Bijoya Kumar
Published: March 2021

This research reports thermoset composites reinforced with cotton and polyester fibers (recovered from pre‐consumer textile waste). The carded web of cotton and polyester fibers and epoxy resin were used to develop the composites using the compression molding technique. The polyester/epoxy composites show average tensile and impact strength higher than cotton/epoxy composites. However, cotton/epoxy composites show average flexural strength higher than polyester/epoxy composites. The bearing strength in a pinned joint for polyester/epoxy composites is higher than cotton/epoxy composites. The equilibrium water content of polyester/epoxy composites was found much less than the corresponding cotton/epoxy composite. The cotton/epoxy and polyester/epoxy composites are thermally stable enough.
Childhood adiposity, adult adiposity, and bone health
Authors: Dong Hongbo , Zhao Xiaoyuan , Cheng Hong , Mi Jie
Published: March 2021

Importance

Childhood and adolescence are critical periods for lifelong bone mineral accrual, but few studies have determined the impact of childhood adiposity on adult bone density.

Objective

To determine the long‐term impact of childhood adiposity on adult areal bone mineral density (aBMD) and the effect of adult adiposity on this relationship.

Methods

We conducted a longitudinal study of 1156 adults (56.3% men), for whom skinfold thickness (SFT) had been measured during childhood (6–18 years) and fat mass percentage (FMP) and aBMD were measured during adulthood (29–43 years). Adult aBMD in the lumbar spine (LS), femoral neck (FN), arms, and legs was measured using dual‐energy X‐ray absorptiometry. The direct effect of childhood SFT and its indirect effect through adult FMP on adult aBMD were estimated using general linear regression and a causal steps approach.

Results

Significant positive associations between childhood SFT and adult aBMD were found in the LS in men (β = 0.089, P = 0.044) and in all the skeletal sites in women. With respect to the adult fat–bone relationship, high adult FMP was associated with low aBMD in most of the sites in men, but with high FN aBMD in women (β = 0.144, P = 0.002). Moreover, suppressive effects of adult FMP on the associations between childhood SFT and adult aBMD in the LS (−34.8%) and legs (−67.1%) of men, and a positive effect on the FN aBMD in women (17.0%) were identified.

Interpretation

Childhood adiposity appears to have a positive long‐term effect on adult aBMD, which may be reduced by adiposity in adult men but reinforced by adiposity in adult women.
A pediatrician‐friendly review of three common behavioral health screeners in pediatric practice: Findings and recommendations
Authors: Trafalis Sandra , Giannini Courtney , Joves Jeremy , Portera Saige , Toyama Hannah , Mehta Anika , Basile Krista , Friedberg Robert D.
Published: March 2021

Behavioral health concerns are surging in pediatric practices. Fortunately, integrated behavioral/medical health clinics are growing and child psychiatrists/psychologists are increasingly embedded in these care settings to help shoulder the clinical load. Routine screening of behavioral health problems in primary care facilities enables early identification and treatment. However, deciding on sound, efficient, and scalable screening measures is sometimes arduous. Accordingly, this article presents a clinician‐friendly review of three common instruments useful in screening pediatric behavioral health concerns including anxiety, depression, and conduct problems. Psychometric findings and clinical applications of the Pediatric Symptom Checklist‐17 (PSC‐17), the Patient Health Questionnaire‐9 (PHQ‐9), and the Screen for Child Anxiety Related Emotional Disorders (SCARED) are delineated. Finally, clinical implications and recommendations for practicing pediatricians and child psychiatrists are offered.
The impact of body weight trajectory from childhood on chronic inflammation in adulthood: The Bogalusa Heart Study
Authors: Yan Yinkun , Li Shengxu , Liu Yang , Bazzano Lydia , He Jiang , Mi Jie , Chen Wei
Published: March 2021

Importance

The impact of long‐term burden of excessive body weight, beginning in childhood, on inflammatory status in adulthood has been poorly described.

Objective

To characterize the longitudinal body mass index (BMI) trajectory from childhood and examine its relationship with inflammatory status in adulthood.

Methods

We included 1285 adults who had 4–15 repeat measurements of BMI from childhood to adulthood. The area under the curve (AUC) of growth curves was calculated to characterize long‐term burden (total AUC) and trends (incremental AUC) of BMI.

Results

After adjusting for covariates, higher values of BMI in terms of childhood and adulthood, as well as total and incremental AUC, were strongly associated with elevated levels of adult C‐reactive protein (CRP) in the four race‐sex groups. There were significant differences in linear and nonlinear curve parameters between the normal and high CRP groups for all race‐sex groups (P < 0.01). Compared with participants who had consistently low BMI in both childhood and adulthood, participants with high BMI in adulthood had higher CRP levels (P < 0.001), irrespective of their childhood BMI status; participants with high BMI in childhood but low BMI in adulthood had similar adult CRP levels.

Interpretation

The impact of excessive body weight on inflammation is cumulative and exacerbated over time. The influence of childhood overweight/obesity on inflammatory status in adulthood can be alleviated by reducing adiposity in adulthood.
Pharmacokinetic variability of factor VIII concentrates in Chinese pediatric patients with moderate or severe hemophilia A
Authors: Chen Zhenping , Huang Kun , Li Gang , Zhen Yingzi , Wu Xinyi , Di Ai , Liu Guoqing , Li Zekun , Alfonso Iorio , Wu Runhui
Published: March 2021

Importance

The use of factor VIII (FVIII) concentrates under pharmacokinetic (PK) guidance has become the main approach for treatment of hemophilia. However, limited PK research has been conducted in Chinese pediatric patients.

Objective

To investigate the PK parameters of various FVIII concentrates in Chinese pediatric patients.

Methods

Seventy‐nine patients were enrolled (28 treated with Kogenate FS®, 23 treated with Advate ®, and 28 treated with GreenMono™). All enrolled patients participated in single‐dose PK analysis after at least a 3‐day washout period. Blood samples were collected predose, as well as at 1 h, 9 h, 24 h, and 48 h after infusion; FVIII levels were measured using a one‐stage clotting assay. von Willebrand Factor Antigen (VWF:Ag) levels and blood types were also determined. PK parameters were evaluated by WAPPS‐Hemo.

Results

Mean values of terminal elimination half‐life time (t1/2) for the Kogenate FS®, Advate®, and GreenMono™ FVIII groups were 12.24 h, 10.18 h, and 9.62 h; median clearance values were 4.16, 6.23, and 5.11 mL·kg−1·h−1; and median in vivo recovery values were 1.97, 1.55, and 1.61 IU/dL per IU/kg. Longer t1/2, higher in vivo recovery, and lower clearance were observed in patients with higher VWF:Ag level who were treated with recombinant concentrates.

Interpretation

Chinese pediatric patients with hemophilia had FVIII PK characteristics similar to those previously observed in non‐Chinese children, including large variation among individuals. VWF:Ag level and FVIII brand were associated with differences in FVIII PK. Thus, PK‐guided dosing should be used to optimize individualized therapy in Chinese children.
Bridging the gap: Can International Consortium of Health Outcomes Measurement standard sets align outcomes accepted for regulatory and health technology assessment decision‐making of oncology medicines
Authors: Kalf Rachel R. J. , Vreman Rick A. , Delnoij Diana M.J. , Bouvy Marcel L. , Goettsch Wim G.
Published: March 2021

Standard outcome sets developed by the International Consortium for Health Outcomes Measurement (ICHOM) facilitate value‐based health care in healthcare practice and have gained traction from regulators and Health Technology Assessment (HTA) agencies that regularly assess the value of new medicines. We aimed to assess the extent to which the outcomes used by regulators and HTA agencies are patient‐relevant, by comparing these to ICHOM standard sets. We conducted a cross‐sectional comparative analysis of ICHOM standard sets, and publicly available regulatory and HTA assessment guidelines. We focused on oncology due to many new medicines being developed, which are accompanied by substantial uncertainty regarding the relevance of these treatments for patients. A comparison of regulatory and HTA assessment guidelines, and ICHOM standard sets showed that both ICHOM and regulators stress the importance of disease‐specific outcomes. On the other hand, HTA agencies have a stronger focus on generic outcomes in order to allow comparisons across disease areas. Overall, similar outcomes are relevant for market access, reimbursement, and in ICHOM standard sets. However, some differences are apparent, such as the acceptability of intermediate outcomes. These are recommended in ICHOM standard sets, but regulators are more likely to accept intermediate outcomes than HTA agencies. A greater level of alignment in outcomes accepted may enhance the efficiency of regulatory and HTA processes, and increase timely access to new medicines. ICHOM standard sets may help align these outcomes. However, some differences in outcomes used may remain due to the different purposes of regulatory and HTA decision‐making.
Periodic dynamics of multidirectional associative neural networks with discontinuous activation functions and mixed time delays
Authors: Zhang Yan , Qiao Yuanhua , Duan Lijuan , Miao Jun , Zhang Jiajia
Published: March 2021

Multidirectional associative memory neural networks (MAMNNs) are constructed to simulate the many‐to‐many association, and they are applied widely in many fields. It is important to explore the global stability of the periodic solution of MAMNNs. In this paper, MAMNNs with discontinuous activation functions and mixed time‐varying delays are considered. Firstly, we investigate the conditions for the existence of the periodic solution by using the Mawhin‐like coincidence theorem, and a special connecting weight matrix is constructed to prove the existence of the periodic solution. Secondly, the uniqueness and global exponential stability of the periodic solution are explored for the non‐self‐connected system by introducing a Lipschitz‐like condition. Finally, numerical simulations are given to illustrate the effectiveness of our main results.
Preparation of Graphene Oxide/Fe3O4 Nanocomposite as a Potential Magnetic Nanocarrier and MRI Contrast Agent
Authors: Sadighian Somayeh , Bayat Nahid , Najaflou Sahar , Kermanian Mehraneh , Hamidi Mehrdad
Published: March 2021

In this paper, graphene oxide/ magnetite (GO/Fe3O4) nanocomposite was synthesized as a carrier and MRI contrast agent. X‐ray diffraction (XRD) indicated that the crystalline structure of Fe3O4 nanoparticles and Furrier transform infrared spectroscopy (FT‐IR) provided evidence for the presence of Fe3O4 and GO in the nanocomposite. The surface morphology of the nanocomposite was studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The magnetic properties of the synthesized nanocomposite was studied by a vibrating sample magnetometer (VSM). The drug loading and encapsulation efficiency of the curcumin were 22 and 96 %, respectively. The comparison between drug release from GO/Fe3O4 in neutral and acidic pH was shown high release in neutral conditions. MTT results demonstrated that the GO/Fe3O4 nanocomposite illustrates considerable toxicity due to which cell viability decreased to lower than 50 % at 140 μg ml−1 concentration. The results showed that curcumin and curcumin loaded nanocomposite has a similar power of antioxidant activities. GO/Fe3O4 nanocomposite is a good magnetic resonance T2 contrast agent under the T2‐imaging sequences. The novelty of this study is the application of water‐dispersed GO/Fe3O4 with pH‐dependent release properties for designing a new colon drug delivery.
Graphene Nanosphere as Advanced Electrode Material to Promote High Performance Symmetrical Supercapacitor
Authors: Yan Zaoxue , Gao Zhihong , Zhang Zongyao , Dai Chengjing , Wei Wei , Shen Pei Kang
Published: March 2021

To get carbon electrode with both excellent gravimetric and volumetric capacitances at high mass loadings is critical to supercapacitors. Herein, cracked defective graphene nanospheres (GNS) well meet above requirements. The morphology and structure of the GNS are controlled by polystyrene sphere template/glucose ratio, microwave heating time, and Fe content. The typical GNS with specific surface area of 2794 m2 g−1, pore volume of 1.48 cm3 g−1, and packing density of 0.74 g cm−3 performs high gravimetric and volumetric capacitances of 529 F g−1 and 392 F cm−3 at 1A g−1 with a capacitance retention of 62.5% at 100 A g−1 in a three‐electrode system in 6 mol L−1 KOH aqueous electrolyte. In a two‐electrode system, the GNS possesses energy density of 18.6 Wh kg−1 (13.8 Wh L−1) at the power density of 504 W kg−1, which is higher than all reported pure carbon materials in gravimetric energy density and higher than all reported heteroatom‐doped carbon materials in volumetric energy density, in aqueous solution, as far as it is known. A structural feature of carbon materials that possess both high energy density and high power density is pointed out here.
High‐fat diet exacerbates lead‐induced blood–brain barrier disruption by disrupting tight junction integrity
Authors: Li Chao , Shi Liang , Wang Yuanbo , Peng Cheng , Wu Lei , Zhang Yanshu , Du Zhongjun
Published: March 2021

Environmental exposure to lead (Pb) can damage to the central nervous system (CNS) in humans. High‐fat diet (HFD) also has been suggested to impair neurocognitive function. Blood–brain barrier (BBB) is a rigorous permeability barrier for maintaining homeostasis of CNS. The damage of BBB caused by tight junctions (TJs) disruption is central to the etiology of various CNS disorders. This study aimed to investigate whether HFD could exacerbate Pb exposure induced the destruction of BBB integrity by TJs disruption. To this end, we measured cell viability assay, trans‐endothelial electrical resistance assay, horseradish peroxidase flux measurement, Western blot analysis, and immunofluorescence experiments. The results showed that palmitic acid (PA), the most common saturated fatty acid found in the human body, can increase the permeability of the BBB in vitro which formed in bEnd.3 cells induced by Pb exposure, and decrease the expression of TJs, such as zonula occludins‐1 (ZO‐1) and occludin. Besides, we found that PA could promote the up‐regulation of matrix metalloproteinase (MMP)‐9 expression and activate the c‐Jun N‐terminal kinase (JNK) pathway induced by Pb. MMP‐9 inhibitor or JNK inhibitor could increase BBB integrity and up‐regulate the expressions of ZO‐1 and occludin after treatment, respectively. Moreover, the JNK inhibitor could down‐regulate the expression of MMP‐9. In conclusion, these results suggested that HFD exacerbates Pb‐induced BBB disruption by disrupting TJs integrity. This may be because PA promotes the activation of JNK pathway and then up‐regulated the expression of MMP‐9 after Pb‐exposure. It is suggested that people with HFD exposed to environmental Pb may cause more serious damage to the CNS.
Creating Superposition: Stern–Gerlach
Authors: Hughes Ciaran , Isaacson Joshua , Perry Anastasia , Sun Ranbel F. , Turner Jessica
Published: March 2021

In the previous chapter, we have seen that a photon in an interferometer can be a prototype for a qubit. Might there be any other prototypes for a qubit arising from other particles that we might know? In fact, an electron is another prototype for a qubit. An electron has many measurable properties such as energy, mass, momentum. But, for the purposes of creating a qubit, we want to focus on a property with only two measurable values. An electron has a two-state property which is called spin.
Generalized Bounded Linear Logic and its Categorical Semantics
Authors: Fukihara Yōji , Katsumata Shin-ya
Published: March 2021

We introduce a generalization of Girard et al.’s called (and its affine variant ). It is designed to capture the core mechanism of dependency in , while it is also able to separate complexity aspects of . The main feature of is to adopt a multi-object pseudo-semiring as a grading system of the !-modality. We analyze the complexity of cut-elimination in , and give a translation from with constraints to with positivity axiom. We then introduce indexed linear exponential comonads (ILEC for short) as a categorical structure for interpreting the $${!}$$
!
-modality of . We give an elementary example of ILEC using folding product, and a technique to modify ILECs with symmetric monoidal comonads. We then consider a semantics of using the folding product on the category of assemblies of a BCI-algebra, and relate the semantics with the realizability category studied by Hofmann, Scott and Dal Lago.
Adjoint Reactive GUI Programming
Authors: Graulund Christian Uldal , Szamozvancev Dmitrij , Krishnaswami Neel
Published: March 2021

Most interaction with a computer is via graphical user interfaces. These are traditionally implemented imperatively, using shared mutable state and callbacks. This is efficient, but is also difficult to reason about and error prone. Functional Reactive Programming (FRP) provides an elegant alternative which allows GUIs to be designed in a declarative fashion. However, most FRP languages are synchronous and continually check for new data. This means that an FRP-style GUI will “wake up” on each program cycle. This is problematic for applications like text editors and browsers, where often nothing happens for extended periods of time, and we want the implementation to sleep until new data arrives. In this paper, we present an asynchronous FRP language for designing GUIs called $$\lambda _{\mathsf {Widget}}$$

λ
Widget

. Our language provides a novel semantics for widgets, the building block of GUIs, which offers both a natural Curry–Howard logical interpretation and an efficient implementation strategy.
A General Semantic Construction of Dependent Refinement Type Systems, Categorically
Authors: Kura Satoshi
Published: March 2021

Dependent refinement types are types equipped with predicates that specify preconditions and postconditions of underlying functional languages. We propose a general semantic construction of dependent refinement type systems from underlying type systems and predicate logic, that is, a construction of liftings of closed comprehension categories from given (underlying) closed comprehension categories and posetal fibrations for predicate logic. We give sufficient conditions to lift structures such as dependent products, dependent sums, computational effects, and recursion from the underlying type systems to dependent refinement type systems. We demonstrate the usage of our construction by giving semantics to a dependent refinement type system and proving soundness.
A Quantified Coalgebraic van Benthem Theorem
Authors: Wild Paul , Schröder Lutz
Published: March 2021

The classical van Benthem theorem characterizes modal logic as the bisimulation-invariant fragment of first-order logic; put differently, modal logic is as expressive as full first-order logic on bisimulation-invariant properties. This result has recently been extended to two flavours of quantitative modal logic, viz. fuzzy modal logic and probabilistic modal logic. In both cases, the quantitative van Benthem theorem states that every formula in the respective quantitative variant of first-order logic that is bisimulation-invariant, in the sense of being nonexpansive w.r.t. behavioural distance, can be approximated by quantitative modal formulae of bounded rank. In the present paper, we unify and generalize these results in three directions: We lift them to full coalgebraic generality, thus covering a wide range of system types including, besides fuzzy and probabilistic transition systems as in the existing examples, e.g. also metric transition systems; and we generalize from real-valued to quantale-valued behavioural distances, e.g. nondeterministic behavioural distances on metric transition systems; and we remove the symmetry assumption on behavioural distances, thus covering also quantitative notions of simulation.
Finding Cut-Offs in Leaderless Rendez-Vous Protocols is Easy
Authors: Balasubramanian A. R. , Esparza Javier , Raskin Mikhail
Published: March 2021

In rendez-vous protocols an arbitrarily large number of indistinguishable finite-state agents interact in pairs. The cut-off problem asks if there exists a number B such that all initial configurations of the protocol with at least B agents in a given initial state can reach a final configuration with all agents in a given final state. In a recent paper [17], Horn and Sangnier prove that the cut-off problem is equivalent to the Petri net reachability problem for protocols with a leader, and in

"Image missing"

for leaderless protocols. Further, for the special class of symmetric protocols they reduce these bounds to

"Image missing"

and

"Image missing"

, respectively. The problem of lowering these upper bounds or finding matching lower bounds is left open. We show that the cut-off problem is

"Image missing"

-complete for leaderless protocols,

"Image missing"

-complete for symmetric protocols with a leader, and in

"Image missing"

for leaderless symmetric protocols, thereby solving all the problems left open in [17].
dtControl 2.0: Explainable Strategy Representation via Decision Tree Learning Steered by Experts
Authors: Ashok Pranav , Jackermeier Mathias , Křetínský Jan , Weinhuber Christoph , Weininger Maximilian , Yadav Mayank
Published: March 2021

Recent advances have shown how decision trees are apt data structures for concisely representing strategies (or controllers) satisfying various objectives. Moreover, they also make the strategy more explainable. The recent tool had provided pipelines with tools supporting strategy synthesis for hybrid systems, such as and . We present , a new version with several fundamentally novel features. Most importantly, the user can now provide domain knowledge to be exploited in the decision tree learning process and can also interactively steer the process based on the dynamically provided information. To this end, we also provide a graphical user interface. It allows for inspection and re-computation of parts of the result, suggesting as well as receiving advice on predicates, and visual simulation of the decision-making process. Besides, we interface model checkers of probabilistic systems, namely and and provide dedicated support for categorical enumeration-type state variables. Consequently, the controllers are more explainable and smaller.
RTLola on Board: Testing Real Driving Emissions on your Phone
Authors: Biewer Sebastian , Finkbeiner Bernd , Hermanns Holger , Köhl Maximilian A. , Schnitzer Yannik , Schwenger Maximilian
Published: March 2021

This paper is about shipping runtime verification to the masses. It presents the crucial technology enabling everyday car owners to monitor the behaviour of their cars in-the-wild. Concretely, we present an Android app that deploys rtlola runtime monitors for the purpose of diagnosing automotive exhaust emissions. For this, it harvests the availability of cheap bluetooth adapters to the On-Board-Diagnostics (obd) ports, which are ubiquitous in cars nowadays. We detail its use in the context of Real Driving Emissions (rde) tests and report on sample runs that helped identify violations of the regulatory framework currently valid in the European Union.
Replicating $$\textsc {Restart}$$ with Prolonged Retrials: An Experimental Report
Authors: Budde Carlos E. , Hartmanns Arnd
Published: March 2021

Statistical model checking uses Monte Carlo simulation to analyse stochastic formal models. It avoids state space explosion, but requires rare event simulation techniques to efficiently estimate very low probabilities. One such technique is $$\textsc {Restart}$$

R

E
S
T
A
R
T

. Villén-Altamirano recently showed—by way of a theoretical study and ad-hoc implementation—that a generalisation of $$\textsc {Restart}$$

R

E
S
T
A
R
T

to prolonged retrials offers improved performance. In this paper, we demonstrate our independent replication of the original experimental results. We implemented $$\textsc {Restart}$$

R

E
S
T
A
R
T

with prolonged retrials in the and tools, and apply them to the models used originally. To do so, we had to resolve ambiguities in the original work, and refine our setup multiple times. We ultimately confirm the previous results, but our experience also highlights the need for precise documentation of experiments to enable replicability in computer science.
cpalockator: Thread-Modular Analysis with Projections
Authors: Andrianov Pavel , Mutilin Vadim , Khoroshilov Alexey
Published: March 2021

Our submission to SV-COMP’21 is based on the software verification framework "Image missing" and implements the extension to the thread-modular approach. It considers every thread separately, but in a special environment which models thread interactions. The environment is expressed by projections of normal transitions in each thread. A projection contains a description of possible effects over shared data and synchronization primitives, as well as conditions of its application. Adjusting the precision of the projections, one can find a balance between the speed and the precision of the whole analysis.

Implementation on the top of the "Image missing" framework allows combining our approach with existing algorithms and analyses. Evaluation on the sv-benchmarks confirms the scalability and soundness of the approach.
Gazer-Theta: LLVM-based Verifier Portfolio with BMC/CEGAR (Competition Contribution)
Authors: Ádám Zsófia , Sallai Gyula , Hajdu Ákos
Published: March 2021

Gazer-Theta is a software model checking toolchain including various analyses for state reachability. The frontend, namely Gazer, supports C programs through an LLVM-based transformation and optimization pipeline. Gazer includes an integrated bounded model checker (BMC) and can also employ the Theta backend, a generic verification framework based on abstraction-refinement (CEGAR). On SV-COMP 2021, a portfolio of BMC, explicit-value analysis, and predicate abstraction is applied sequentially in this order.
Goblint: Thread-Modular Abstract Interpretation Using Side-Effecting Constraints
Authors: Saan Simmo , Schwarz Michael , Apinis Kalmer , Erhard Julian , Seidl Helmut , Vogler Ralf , Vojdani Vesal
Published: March 2021

Goblintis a static analysis framework for C programs specializing in data race analysis. It relies on thread-modular abstract interpretation where thread interferences are accounted for by means of flow-insensitive global invariants.
Graded Modal Dependent Type Theory
Authors: Moon Benjamin , Eades III Harley , Orchard Dominic
Published: March 2021

Graded type theories are an emerging paradigm for augmenting the reasoning power of types with parameterizable, fine-grained analyses of program properties. There have been many such theories in recent years which equip a type theory with quantitative dataflow tracking, usually via a semiring-like structure which provides analysis on variables (often called ‘quantitative’ or ‘coeffect’ theories). We present Graded Modal Dependent Type Theory (Grttfor short), which equips a dependent type theory with a general, parameterizable analysis of the flow of data, both in and between computational terms and types. In this theory, it is possible to study, restrict, and reason about data use in programs and types, enabling, for example, parametric quantifiers and linearity to be captured in a dependent setting. We proposeGrtt, study its metatheory, and explore various case studies of its use in reasoning about programs and studying other type theories. We have implemented the theory and highlight the interesting details, including showing an application of grading to optimising the type checking procedure itself.
Strong-Separation Logic
Authors: Pagel Jens , Zuleger Florian
Published: March 2021

Most automated verifiers for separation logic are based on the symbolic-heap fragment, which disallows both the magic-wand operator and the application of classical Boolean operators to spatial formulas. This is not surprising, as support for the magic wand quickly leads to undecidability, especially when combined with inductive predicates for reasoning about data structures. To circumvent these undecidability results, we propose assigning a more restrictive semantics to the separating conjunction. We argue that the resulting logic, strong-separation logic, can be used for symbolic execution and abductive reasoning just like “standard” separation logic, while remaining decidable even in the presence of both the magic wand and the list-segment predicate—a combination of features that leads to undecidability for the standard semantics.
Graded Hoare Logic and its Categorical Semantics
Authors: Gaboardi Marco , Katsumata Shin-ya , Orchard Dominic , Sato Tetsuya
Published: March 2021

Deductive verification techniques based on program logics (i.e., the family of Floyd-Hoare logics) are a powerful approach for program reasoning. Recently, there has been a trend of increasing the expressive power of such logics by augmenting their rules with additional information to reason about program side-effects. For example, general program logics have been augmented with cost analyses, logics for probabilistic computations have been augmented with estimate measures, and logics for differential privacy with indistinguishability bounds. In this work, we unify these various approaches via the paradigm of grading, adapted from the world of functional calculi and semantics. We propose Graded Hoare Logic (GHL), a parameterisable framework for augmenting program logics with a preordered monoidal analysis. We develop a semantic framework for modelling GHL such that grading, logical assertions (pre- and post-conditions) and the underlying effectful semantics of an imperative language can be integrated together. Central to our framework is the notion of a graded category which we extend here, introducing graded Freyd categories which provide a semantics that can interpret many examples of augmented program logics from the literature. We leverage coherent fibrations to model the base assertion language, and thus the overall setting is also fibrational.
Weighted approximate Bayesian computation via Sanov’s theorem
Authors: Viscardi Cecilia , Boreale Michele , Corradi Fabio
Published: March 2021

We consider the problem of sample degeneracy in Approximate Bayesian Computation. It arises when proposed values of the parameters, once given as input to the generative model, rarely lead to simulations resembling the observed data and are hence discarded. Such “poor” parameter proposals do not contribute at all to the representation of the parameter’s posterior distribution. This leads to a very large number of required simulations and/or a waste of computational resources, as well as to distortions in the computed posterior distribution. To mitigate this problem, we propose an algorithm, referred to as the Large Deviations Weighted Approximate Bayesian Computation algorithm, where, via Sanov’s Theorem, strictly positive weights are computed for all proposed parameters, thus avoiding the rejection step altogether. In order to derive a computable asymptotic approximation from Sanov’s result, we adopt the information theoretic “method of types” formulation of the method of Large Deviations, thus restricting our attention to models for i.i.d. discrete random variables. Finally, we experimentally evaluate our method through a proof-of-concept implementation.
Spatial Indicators to Monitor Land Consumption for local Governance in Southern Germany
Authors: Meyer Markus A. , Lehmann Isabella , Seibert Otmar , Früh-Müller Andrea
Published: March 2021

Land consumption for settlement and infrastructure development has been extensively discussed and analyzed in the last two decades. In Germany, existing governance at the state level seems to hardly foster effective land management at the municipal level to achieve overarching goals at the level of the European Union such as “no net land take”. Germany aims to limit land consumption to less than 30 ha per day by 2030. This goal is hardly translated to the municipal level where actual land-use decisions are taken due to the municipal planning sovereignty. In order to address these deficiencies, this study characterizes land consumption in the Nuremberg Metropolitan Region with self-organizing maps and identifies major factors explaining cluster differences using boosted regression trees. We identified four major clusters: booming, prosperous, moderate, and transition regions. Generally, beneficial demographics (population growth and lower old-age dependency ratio) and financial power of municipalities come at the expense of considerable settlement and traffic infrastructure development (i.e., increased land consumption), creating the impression of a rather unregulated market despite the existing planning framework in Germany. Based on these clusters, we developed an indicator set through a participatory process to improve land-use planning following three dimensions: efficient land use, preservation of cultural landscapes and its services, and fostering the regional added value of agricultural products beyond the current local political focus. Future research should assess whether municipalities with better information will reduce land consumption due to increased awareness.
Assessing the learning curve associated with a novel flexible robot in the pre-clinical and clinical setting
Authors: Zhu Toby S. , Godse Neal , Clayburgh Daniel R. , Duvvuri Umamaheswar
Published: March 2021

Background

Transoral robotic surgery has been successfully used by head and neck surgeons for a variety of procedures but is limited by rigid instrumentation and line-of-sight visualization. Non-linear systems specifically designed for the aerodigestive tract are needed. Ease of use of these new systems in both training and clinical environments is critical in its widespread adoption.

Methods

Residents, fellows, and junior faculty performed four tasks on an anatomical airway mannequin using the Medrobotics FLEX™ Robotic System: expose and incise the tonsil, grasp the epiglottis, palpate the vocal processes, and grasp the interarytenoid space. These tasks were performed once a day for four days; after a 4-month time gap, subjects were asked to perform these same tasks for three more days. Time to task completion and total distance driven were tracked. In addition, a retrospective analysis was performed analyzing one attending physician’s experience with clinical usage of the robot.

Results

13 subjects completed the initial round of the mannequin simulation and 8 subjects completed the additional testing 4 months later. Subjects rapidly improved their speed and efficiency at task completion. Junior residents were slower in most tasks initially compared to senior trainees but quickly reached similar levels of efficiency. Following the break there was minimal degradation in skills and continued improvement in efficiency was observed with additional trials. There was significant heterogeneity in the analyzed clinical cases, but when analyzing cases of similar complexity and pathology, clear decreases in overall operative times were demonstrable.

Conclusion

Novice users quickly gained proficiency with the FLEX™ Robotic System in a training environment, and these skills are retained after several months. This learning could translate to the clinical setting if a proper training regimen is developed. The Medrobotics FLEX™ Robotic System shows promise as a surgical tool in head and neck surgery in this study.
An extension of the strain transfer principle for fiber reinforced materials
Authors: Ospald Felix , Bergermann Kai , Herzog Roland
Published: March 2021

Fiber optical strain sensors are used to measure the strain at a particular sensor position inside the fiber. In order to deduce the strain in the surrounding matrix material, one can employ the strain transfer principle. Its application is based on the assumption that the presence of the fiber does not impede the deformation of the matrix material in fiber direction. In fact, the strain transfer principle implies that the strain in fiber direction inside the fiber carries over verbatim to the strain inside the matrix material. For a comparatively soft matrix material, however, this underlying assumption may not be valid. To overcome this drawback, we propose to superimpose the matrix material with a one-dimensional model of the fiber, which takes into account its elastic properties. The finite element solution of this model yields a more accurate prediction of the strain inside the fiber in fiber direction at low computational costs.
Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis (NASH) in the United Kingdom (UK) in 2018
Authors: Morgan Alice , Hartmanis Sally , Tsochatzis Emmanuel , Newsome Philip N. , Ryder Stephen D. , Elliott Rachel , Floros Lefteris , Hall Richard , Higgins Victoria , Stanley George , Cure Sandrine , Vasudevan Sharad , Pezzullo Lynne
Published: March 2021

Background and aims

Non-alcoholic steatohepatitis (NASH) – a progressive subset of non-alcoholic fatty liver disease (NAFLD) – is a chronic liver disease that can progress to advanced fibrosis, cirrhosis, and end-stage liver disease (ESLD) if left untreated. Early-stage NASH is usually asymptomatic, meaning a large proportion of the prevalent population are undiagnosed. Receiving a NASH diagnosis increases the probability that a patient will receive interventions for the purpose of managing their condition. The purpose of this study was to estimate the disease burden and economic impact of diagnosed NASH in the United Kingdom (UK) adult population in 2018.

Methods

The socioeconomic burden of diagnosed NASH from a societal perspective was estimated using cost-of-illness methodology applying a prevalence approach. This involved estimating the number of adults with diagnosed NASH in the UK in a base period (2018) and the economic and wellbeing costs attributable to diagnosed NASH in that period. The analysis was based on a targeted review of the scientific literature, existing databases and consultation with clinical experts, health economists and patient groups.

Results

Of the prevalent NASH population in the UK in 2018, an estimated 79.8% were not diagnosed. In particular, of the prevalent population in disease stages F0 to F2, only 2.0% (F0), 2.0% (F1) and 16.5% (F2), respectively, were diagnosed. Total economic costs of diagnosed NASH in the UK ranged from £2.3 billion (lower prevalence scenario, base probability of diagnosis scenario) to £4.2 billion (higher prevalence scenario, base probability of diagnosis scenario). In 2018, people with NASH in the UK were estimated to experience 94,094 to 174,564 disability-adjusted life years (DALYs) overall. Total wellbeing costs associated with NASH in 2018 were estimated to range between £5.6 to £10.5 billion.

Conclusion

The prevention and appropriate management of adult NASH patients could result in reduced economic costs and improvements in wellbeing.
The butterfly effect in clinical supervision
Authors: Klasen Jennifer M. , Lingard Lorelei A.
Published: March 2021

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