bluuebunny/crossref_metadata_2025 huggingface dataset:
Revision of the Stochastically Perturbed Parametrisations model uncertainty scheme in the Integrated Forecasting System
Authors: Lang Simon T. K. , Lock Sarah‐Jane , Leutbecher Martin , Bechtold Peter , Forbes Richard M.
Published: January 2021

The Stochastically Perturbed Parametrisations scheme (SPP) represents model uncertainty in numerical weather prediction by introducing stochastic perturbations into the physical parametrisation schemes. The perturbations are constructed in such a way that the internal consistency of the physical parametrisation schemes is preserved. We developed a revised version of SPP for the Integrated Forecasting System of the European Centre for Medium‐Range Weather Forecasts (ECMWF). The revised version introduces perturbations to additional quantities and modifies the probability distributions sampled by the scheme. Medium‐range ensemble forecasts with the revised SPP are considerably more skilful than ensemble forecasts with the original implementation of SPP. The revised version of SPP is similar, in terms of forecast skill, to the Stochastically Perturbed Parametrisation Tendency scheme (SPPT), which is currently used to represent model uncertainty in the operational ECMWF ensemble forecasts.
Detection and longitudinal distribution of GW1516 and its metabolites in equine hair for doping control using liquid chromatography/high‐resolution mass spectrometry
Authors: Ishii Hideaki , Shibuya Mariko , Leung Gary Ngai‐Wa , Nozawa Satoshi , Yamashita Shozo , Yamada Masayuki , Kushiro Asuka , Kasashima Yoshinori , Okada Jun , Kawasaki Kazumi , Kijima‐Suda Isao
Published: January 2021

Rationale

GW1516 is a peroxisome proliferator‐activated receptor‐δ (PPAR‐δ) agonist that is banned in horseracing and equestrian sports. Long‐term detection and longitudinal distribution of GW1516 in the mane of a horse are reported for the first time and this hair analysis could prolong the detection window of GW1516 for doping control.

Methods

Mane hairs were divided into three segments (0–7, 7–15, and >15 cm from the cut end) and completely pulverized and homogenized for analysis. The pulverized hair samples were extracted with methanol followed by further purification and the extracts were analyzed by liquid chromatography/electrospray ionization high‐resolution mass spectrometry (LC/ESI‐HRMS) using a Q‐Exactive instrument. This method was successfully validated and applied to post‐administration samples to confirm the presence of GW1516 and its metabolites and estimate the uptake amounts of GW1516.

Results

After administration of 150 mg of GW1516 to a thoroughbred mare, GW1516 was detected in one of two segments of all mane hairs, and four metabolites, namely GW1516 sulfoxide, GW1516 sulfone, 5‐(hydroxymethyl)‐4‐methyl‐2‐(4‐trifluoromethylphenyl)thiazole (HMTT), and 4‐methyl‐2‐[4‐(trifluoromethyl)phenyl]‐1,3‐thiazole‐5‐carboxylic acid (MTTC), were also identified. The longitudinal distribution analysis results showed that the maximum uptake of GW1516 into hair (approximately 0.05 pg/mg) was observed at around 13 weeks post‐administration and GW1516 could be detected and confirmed up to 6 months post‐administration.

Conclusions

The parent drug GW1516 was identified as the most appropriate monitoring target in equine hair for controlling its misuse in horses. The use of hair analysis could extend the detection time of GW1516 to at least 6 months after the administration of 150 mg of GW1516 to a thoroughbred mare.
Stories of a Healing Way: A Navajo Woman’s Media Production for Cultural Representation and Identification
Authors: Guzzetti Barbara J.
Published: January 2021

Little research has been conducted on the multimodal writing of contemporary Native American women that would refute stereotypical and outdated notions of Indigenous peoples as a dying population. This case study was undertaken to address that gap in the extant research by examining the writing practices of a young Native American woman to determine why and how she composed and participated in participatory media of personal zines and social media to represent her gender and cultural identities. The inquiry was conducted from multiple perspectives of literacy as a social and semiotic practice, the new literacies, tribal critical race theory, and Indigenous feminist theory. Data were triangulated by observations, formal and informal interviews, questionnaires, screenshots, and the participant’s video recordings of her storytelling. I analyzed these data by thematic and semiotic analyses. Findings demonstrated how she crafted comic strip stories and do‐it‐yourself media to create, teach, and preserve Navajo customs and language as a living culture through story lines, settings, illustrations, genre, and teaching devices in her zines. Descriptions are provided of how Navajo women were positioned as strong and independent participants in traditional and contemporary life. Results revealed the ways in which a Navajo woman engaged in practices of the new literacies for resistance against gender and cultural oppression and colonization. Implications are drawn for positioning Native American women within contemporary culture and for culturally responsive literacy education.
A Multifunctional Nanovaccine based on L‐Arginine‐Loaded Black Mesoporous Titania: Ultrasound‐Triggered Synergistic Cancer Sonodynamic Therapy/Gas Therapy/Immunotherapy with Remarkably Enhanced Efficacy
Authors: Wang Meifang , Hou Zhiyao , Liu Sainan , Liang Shuang , Ding Binbin , Zhao Yajie , Chang Mengyu , Han Gang , Kheraif Abdulaziz A. Al , Lin Jun
Published: January 2021

In order to achieve better antitumor therapeutic efficacy and inhibit tumor metastasis, a multifunctional nanovaccine based on L‐arginine (LA)‐loaded black mesoporous titania (BMT) is fabricated. In this system, LA is utilized as the exogenous NO supplementation for gas therapy, and BMT is served as acoustic sensitizer for sonodynamic therapy. The ultrasound (US) as the exogenous stimulus can simultaneously trigger BMT and LA to produce singlet oxygen (1O2) and NO gas at tumor sites, respectively. Interestingly, 1O2 from US‐excited BMT can promote the oxidation of LA to produce more NO. The high concentration of 1O2 and NO in cancer cell can cause intracellular strong oxidative stress level and DNA double‐strand breaks to induce cancer cell apoptosis ultimately. The US‐triggered BMT@LA “nanovaccine” combining with immune checkpoint inhibitor PD‐L1 antibody (αPD‐L1) can induce strong antitumor immune response thus effectively killing primary tumors and further inhibiting metastatic tumors. Hence, BMT@LA‐based “nanovaccine” combining with αPD‐L1 checkpoint blockade treatment can realize synergetic sonodynamic/gas/immunotherapy with enhanced antitumor therapeutic effects.
Study of the Growth Mechanism of Solution‐Synthesized Symmetric Tellurium Nanoflakes at Atomic Resolution
Authors: Li Chen , Zhang Lei , Gong Tian , Cheng Yongfa , Li Luying , Li Li , Jia Shuangfeng , Qi Yajun , Wang Jianbo , Gao Yihua
Published: January 2021

As a new member of 2D materials, 2D tellurium (Te) has recently attracted much attention due to its intriguing properties. Through hydrothermal processing, 2D Te with tunable thickness and size has been realized, and its growth mechanism has also been studied. However, the tailored growth of 2D Te nanoflakes with symmetrical morphologies and interfacial moiré fringes has never been reported. Here, 2D Te nanoflakes have been prepared using the hydrothermal method, and mirror‐symmetrical shapes (including “V‐shape,” “heart‐shape,” and “paper airplane‐shape”) with obvious moiré fringes in the middle of the nanoflakes are observed. Comprehensive transmission electron microscopy (TEM) techniques are utilized for structural characterization of these nanoflakes, especially the moiré fringes in the symmetry axis region of the nanoflakes. The systematic analyses of the moiré fringes and the observation of obvious overlapping edges of the composing nanoflakes from the cross‐sectional samples reveal the possible mechanism of morphological evolution for these symmetrical nanoflakes. These details may fill the research gap in the controllable growth of 2D Te nanomaterials, pave the way for the fabrication of 2D Te moiré superlattices and in‐plane homojunctions, and promote their future versatile applications.
Structural Variation and Switchable Nonlinear Optical Behavior of Metal–Organic Frameworks
Authors: Zhang Lin , Li Hongjun , He Huajun , Yang Yu , Cui Yuanjing , Qian Guodong
Published: January 2021

Two europium metal–organic frameworks (MOFs) based on the same ligand, named as ZJU‐23‐Eu and ZJU‐24‐Eu, are selectively synthesized by fine‐tuning solvent contents to tailor the coordination modes. Eu atoms are eight‐coordinated and nine‐coordinated in ZJU‐23‐Eu and ZJU‐24‐Eu respectively, and their frameworks vary in both spatial connectivity and symmetry. The ligand not only has multiphoton response but also suitable triplet energy level (19 998 cm−1) to sensitize Eu3+. Thus ZJU‐23‐Eu exhibits characteristic emission of Eu3+ peaking at 614 nm via the energy transfer from the two‐/three‐photon excited ligand to Eu3+, with its bidimensional layered structure benefiting this process. In contrast, the changed spatial connectivity in tridimensional ZJU‐24‐Eu narrows the distances between adjacent Eu3+ ions and reduces the density, resulting in poor two‐photon excited fluorescence. Besides, noncentrosymmetric ZJU‐24‐Eu shows second harmonic generation (SHG) response with an intensity of ≈6.2 times relative to KH2PO4 (KDP) microcrystalline powder while centrosymmetric ZJU‐23‐Eu cannot. These results have established two nonlinear optical (NLO) models based on MOFs to synchronously analyze the effects of two structural variables on different NLO behaviors, and provide ingenious ways to design MOF‐based NLO devices with function on demand.
NRL
−/− gene edited human embryonic stem cells generate rod-deficient retinal organoids enriched in S-cone-like photoreceptors
Authors: Cuevas Elisa , Holder Daniel L. , Alshehri Ashwak H. , Tréguier Julie , Lakowski Jörn , Sowden Jane C.
Published: January 2021

Organoid cultures represent a unique tool to investigate the developmental complexity of tissues like the human retina. NRL is a transcription factor required for the specification and homeostasis of mammalian rod photoreceptors. In Nrl-deficient mice, photoreceptor precursor cells do not differentiate into rods, and instead follow a default photoreceptor specification pathway to generate S-cone-like cells. To investigate whether this genetic switch mechanism is conserved in humans, we used CRISPR/Cas9 gene editing to engineer an NRL-deficient embryonic stem cell (ESC) line (NRL−/−), and differentiated it into retinal organoids. Retinal organoids self-organize and resemble embryonic optic vesicles (OVs) that recapitulate the natural histogenesis of rods and cone photoreceptors. NRL−/− OVs develop comparably to controls, and exhibit a laminated, organized retinal structure with markers of photoreceptor synaptogenesis. Using immunohistochemistry and quantitative polymerase chain reaction (qPCR), we observed that NRL−/− OVs do not express NRL, or other rod photoreceptor markers directly or indirectly regulated by NRL. On the contrary, they show an abnormal number of photoreceptors positive for S-OPSIN, which define a primordial subtype of cone, and overexpress other cone genes indicating a conserved molecular switch in mammals. This study represents the first evidence in a human in vitro ESC-derived organoid system that NRL is required to define rod identity, and that in its absence S-cone-like cells develop as the default photoreceptor cell type. It shows how gene edited retinal organoids provide a useful system to investigate human photoreceptor specification, relevant for efforts to generate cells for transplantation in retinal degenerative diseases.
Influence of fiber orientation on the behavior of fiber reinforced concrete slabs
Authors: Conforti Antonio , Cuenca Estefania , Zerbino Raúl , Plizzari Giovanni A.
Published: January 2021

After several decades of research studies, design rules for fiber reinforced concrete (FRC) are now available for several structural elements. Starting from standard tests, it is possible to determine design parameters and constitutive laws to perform simplified sectional verifications and/or numerical analyses. However, one of the main issues still open is represented by the fiber orientation in the real structure that could be different from the one present in standard tests. For this reason, building codes take into account orientation factors to modify the standard material properties. The present paper aims to shed some new lights on the effects of the orientation of steel and macro‐synthetic fibers on the local variability of FRC residual strength properties in slabs made with two concretes: Vibrated (slump of 80 ± 20 mm, V‐FRC) and self‐compacting concrete (slump flow diameter of 700 ± 50 mm, SC‐FRC). In V‐FRC slabs, the orientation of polymer fibers was more influenced by pouring and compaction process compared to steel ones. In SC‐FRC slabs, the flow and wall effects resulted more significant when long steel fibers were used. The post‐cracking performances locally determined in different points of slabs were compared against the ones obtained on standard beams as well. Finally, the global response of these slabs was numerically studied by considering two different support configurations: simply‐supported slabs and slabs on grade.
An Online Acquaintance Community: The Emergence of Chinese Virtual Civility
Authors: Tian Xiaoli , Guo Yanan
Published: January 2021

How is social etiquette performed when offline interpersonal interactions are mediated online? Sixty semi‐structured interviews with WeChat users, China's most popular social media platform, show that the app's technical designs facilitated a set of online etiquette rules which reproduced those of acquaintance communities. Three dimensions of social etiquette rules were considered and observed: respect, elegance, and tidiness. Users honored the face of others and avoided causing others to lose face, often presented a positive but restrained self‐image, and strived to preserve the tidiness of the online public space by avoiding the sharing of and exposing others to “negative energy.” A video abstract is available at https://youtu.be/2tG40y8J11E.
The association of circulating amylin with β‐amyloid in familial Alzheimer's disease
Authors: Ly Han , Verma Nirmal , Sharma Savita , Kotiya Deepak , Despa Sanda , Abner Erin L. , Nelson Peter T. , Jicha Gregory A. , Wilcock Donna M. , Goldstein Larry B. , Guerreiro Rita , Brás José , Hanson Angela J. , Craft Suzanne , Murray Andrew J. , Biessels Geert Jan , Troakes Claire , Zetterberg Henrik , Hardy John , Lashley Tammaryn , AESG  , Despa Florin
Published: January 2021

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected APP/PS1 rats against AD‐associated effects. In contrast, hypersecretion or intravenous injection of human amylin in APP/PS1 rats exacerbated AD‐like pathology through disruption of CSF‐brain Aβ exchange and amylin‐Aβ cross‐seeding.

Discussion

These findings strengthened the hypothesis of circulating amylin‐AD interaction and suggest that modulation of blood amylin levels may alter Aβ‐related pathology/symptoms.
Nanobody—A versatile tool for cancer diagnosis and therapeutics
Authors: Liu Manman , Li Li , Jin Duo , Liu Yangzhong
Published: January 2021

In spite of the successful use of monoclonal antibodies (mAbs) in clinic for tumor treatment, their applications are still hampered in therapeutic development due to limitations, such as tumor penetration and high cost of manufacture. Nanobody, a single domain antibody that holds the strong antigen targeting and binding capacity, has demonstrated various advantages relative to antibody. Nanobody is considered as a next‐generation of antibody‐derived tool in the antigen related recognition and modulation. A number of nanobodies have been developed and evaluated in different stages of clinical trials for cancer treatment. Here we summarized the current progress of nanobody in tumor diagnosis and therapeutics, particularly on the conjugation of nanobody with functional moieties. The nanobody conjugation of diagnostic agents, such as radionuclide and optical tracers, can achieve specific tumor imaging. The nanobody‐drug conjugates can enhance the therapeutic efficacy of anti‐tumor drugs and reduce the adverse effects. The decoration of nanobody on nanodrug delivery systems can further improve the drug targeting to specific tumors.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Synthesis and Coordination Behaviour of a Novel Tridentate P,N,O‐Ketiminate Ligand
Authors: Halz Jan Henrik , Hentsch Andreas , Wagner Christoph , Merzweiler Kurt
Published: January 2021

Treatment of o‐(diphenylphosphino)aniline with 3‐formylacetylacetone led to the formation of the ketimine type Schiff base 3‐((o‐diphenylphosphino‐phenylamino)‐methylene)‐pentane‐2,4‐dione (o−PPh2−C6H4−NH−CH=C(COCH3)2, HL). Complexes [ML2] (M=Fe, Co, Ni, Cu) were obtained from the reaction of HL with the corresponding metal acetate or acetylacetonate derivatives. The [ML2] complexes (M=Fe, Co, Ni) exhibit a distorted octahedral coordination from two tridentate P,N,O ketiminate ligands L−. The arrangement of the ligands is meridional in the case of [FeL2] and [NiL2]. The cobalt complex [CoL2] displays a facial coordination. In the case of the nearly square planar copper complex [CuL2], only the ketiminate functionalities of the ligands are involved in coordination and the participation of the PPh2 groups is neglectable.
Building a Multicultural Society by Political Integration
Authors: Linder Wolf , Mueller Sean
Published: January 2021

This chapter explains how, despite the absence of single ethnic culture, Swiss state- and nation-building was possible. Neither the Swiss nation, nor the Swiss society existed when modern Switzerland was founded in 1848, after a brief civil war. The chapter provides a reading of Swiss history since then as one of gradually achieving the participation of the most important minority groups and the different social classes through proportional representation. Beginning with the losers of the civil war, the Catholic-Conservatives, followed by Protestant farmers and the petite bourgeoise, and ending with the Social-Democrats, the Swiss thus invented the ‘magic formula’ in 1959 for proportionally sharing the seven seats in the federal government. Even the rise of right-wing populism since the 1990s has not changed this basic feature.
Renormalization Group evolution from on-shell SMEFT
Authors: Jiang Minyuan , Ma Teng , Shu Jing
Published: January 2021

Abstract

We describe the on-shell method to derive the Renormalization Group (RG) evolution of Wilson coefficients of high dimensional operators at one loop, which is a necessary part in the on-shell construction of the Standard Model Effective Field Theory (SMEFT), and exceptionally efficient based on the amplitude basis in hand. The UV divergence is obtained by firstly calculating the coefficients of scalar bubble integrals by unitary cuts, then subtracting the IR divergence in the massless bubbles, which can be easily read from the collinear factors we obtained for the Standard Model fields. Examples of deriving the anomalous dimensions at dimension six are presented in a pedagogical manner. We also give the results of contributions from the dimension-8 H4D4 operators to the running of V+V−H2 operators, as well as the running of B+B−H2D2n from H4D2n+4 for general n.
κ-Minkowski-deformation of U(1) gauge theory
Authors: Kupriyanov V. G. , Kurkov M. , Vitale P.
Published: January 2021

Abstract

We construct a noncommutative kappa-Minkowski deformation of U(1) gauge theory, following a general approach, recently proposed in JHEP 08 (2020) 041. We obtain an exact (all orders in the non-commutativity parameter) expression for both the deformed gauge transformations and the deformed field strength, which is covariant under these transformations. The corresponding Yang-Mills Lagrangian is gauge covariant and reproduces the Maxwell Lagrangian in the commutative limit. Gauge invariance of the action functional requires a non-trivial integration measure which, in the commutative limit, does not reduce to the trivial one. We discuss the physical meaning of such a nontrivial commutative limit, relating it to a nontrivial space-time curvature of the undeformed theory. Moreover, we propose a rescaled kappa-Minkowski noncommutative structure, which exhibits a standard flat commutative limit.
Higgsing towards E-strings
Authors: Kim Joonho , Kim Seok , Lee Kimyeong
Published: January 2021

Abstract

We explore 6d (1, 0) superconformal field theories with SU(3) and SU(2) gauge symmetries which cascade after Higgsing to the E-string theory on a single M5 near an E8 wall. Specifically, we study the 2d $$ \mathcal{N} $$
N
= (0, 4) gauge theories which describe self-dual strings of these 6d theories. The self-dual strings can be also viewed as instanton string solitons of 6d Yang-Mills theories. We find the 2d anomaly-free gauge theories for self-dual strings, amending the naive ADHM gauge theories which are anomalous, and calculate their elliptic genera. While these 2d theories respect the flavor symmetry of each 6d SCFT only partially, their elliptic genera manifest the symmetry fully as these functions as BPS index are invariant in strongly coupled IR limit. Our consistent 2d (0, 4) gauge theories also provide new insights on the non-linear sigma models for the instanton strings, providing novel UV completions of the small instanton singularities. Finally, we construct new 2d quiver gauge theories for the self-dual strings in 6d E-string theory for multiple M5-branes probing the E8 wall, and find their fully refined elliptic genera.
Almost conservation laws for stochastic nonlinear Schrödinger equations
Authors: Cheung Kelvin , Li Guopeng , Oh Tadahiro
Published: January 2021

In this paper, we present a globalization argument for stochastic nonlinear dispersive PDEs with additive noises by adapting theI-method (= the method of almost conservation laws) to the stochastic setting. As a model example, we consider the defocusing stochastic cubic nonlinear Schrödinger equation (SNLS) on$${\mathbb {R}}^3$$R3with additive stochastic forcing, white in time and correlated in space, such that the noise lies below the energy space. By combining theI-method with Ito’s lemma and a stopping time argument, we construct global-in-time dynamics for SNLS below the energy space.
Free labor mobility and indeterminacy in models of neoclassical growth
Authors: Parello Carmelo Pierpaolo
Published: January 2021

This paper establishes the conditions under which indeterminacy can occur in a Neoclassical growth model with international labor mobility. In the model, workers are supposed to move freely across countries without restrictions, and according to a Harris–Todaro mechanism that makes migration flows sensitive to differences among labor markets conditions. The paper shows that indeterminacy requires the marginal returns to immigrant labor to be diminishing, and no need for productivity externalities at a social level. It also shows that immigration quotas can serve it well to eliminate indeterminacy and stabilize final output.
Expanding the genetic spectrum of primary familial brain calcification due to SLC2OA2 mutations: a case series
Authors: Magistrelli Luca , Croce Roberta , De Marchi Fabiola , Basagni Chiara , Carecchio Miryam , Nasuelli Nicola , Cantello Roberto , Invernizzi Federica , Garavaglia Barbara , Comi Cristoforo , Mazzini Letizia , D’Alfonso Sandra , Corrado Lucia
Published: January 2021

Primary familial brain calcification (PFBC) is a neurological condition characterized by the presence of intracranial calcifications, mainly involving basal ganglia, thalamus, and dentate nuclei. So far, six genes have been linked to this condition: SLC20A2, PDGFRB, PDGFB, and XPR1 inherited as autosomal-dominant trait, while MYORG and JAM2 present a recessive pattern of inheritance. Patients mainly present with movement disorders, psychiatric disturbances, and cognitive decline or are completely asymptomatic and calcifications may represent an occasional finding. Here we present three variants in SLC20A2, two exonic and one intronic, which we found in patients with PFBC associated to three different clinical phenotypes. One variant is novel and two were already described as variants of uncertain significance. We confirm the pathogenicity of these three variants and suggest a broadening of the phenotypic spectrum associated with mutations in SLC20A2.
European Union legislation on macroalgae products
Authors: Lähteenmäki-Uutela Anu , Rahikainen Moona , Camarena-Gómez María Teresa , Piiparinen Jonna , Spilling Kristian , Yang Baoru
Published: January 2021

Macroalgae-based products are increasing in demand also in Europe. In the European Union, each category of macroalgae-based products is regulated separately. We discuss EU legislation, including the law on medicinal products, foods including food supplements and food additives, feed and feed additives, cosmetics, packaging materials, fertilizers and biostimulants, as well as biofuels. Product safety and consumer protection are the priorities with any new products. Macroalgae products can be sold as traditional herbal medicines. The novel food regulation applies to macroalgae foods that have not previously been used as food, and organic macroalgae are a specific regulatory category. The maximum levels of heavy metals may be a barrier for macroalgae foods, feeds, and fertilizers. Getting health claims approved for foods based on macroalgae is demanding. In addition to the rules on products, the macroalgae business is strongly impacted by the elements of the general regulatory environment such as agricultural/aquacultural subsidies, maritime spatial planning and aquaculture licensing, public procurement criteria, tax schemes, and trade agreements.
Help-Seeking Behavior and Treatment Barriers in Anxiety Disorders: Results from a Representative German Community Survey
Authors: Heinig Ingmar , Wittchen Hans-Ulrich , Knappe Susanne
Published: January 2021

Although effective therapies exist, treatment rates of anxiety disorders (AD) are low, raising the question why affected individuals do not receive treatment. We provide data from the nationally representative German Health Interview and Examination Survey-2011 (DEGS1) on the help-seeking behavior and perceived treatment barriers of 650 subjects with Diagnostic and Statistical Manual of Mental Disorders’ (DSM-IV AD). Only 26% of all cases with AD in the community reported having had contact with mental health services because of their anxiety problems in their lifetime. 16% were currently receiving professional help, most frequently by psychotherapists (8%), psychiatrists (5%) and general practitioners (5%). 40% of all cases never even considered seeking help and 31% reported barriers to treatment, such as self-reliance (18%) or beliefs that treatments were ineffective (9%), unavailable (8%) or too stigmatizing (7%). Measures to increase treatment rates should thus target individual as well as public attitudes and health literacy to increase awareness of and access to evidence-based interventions.
Pesticide exposure affects reproductive capacity of common toads (Bufo bufo) in a viticultural landscape
Authors: Adams Elena , Leeb Christoph , Brühl Carsten A.
Published: January 2021

Amphibian populations are declining worldwide at alarming rates. Among the large variety of contributing stressors, chemical pollutants like pesticides have been identified as a major factor for this decline. Besides direct effects on aquatic and terrestrial amphibian stages, sublethal effects like impairments in reproduction can affect a population. Therefore, we investigated the reproductive capacity of common toads (Bufo bufo) in the pesticide-intensive viticultural landscape of Palatinate in Southwest Germany along a pesticide gradient. In a semi-field study, we captured reproductively active common toad pairs of five breeding ponds with different pesticide contamination level and kept them in a net cage until spawning. Toads from more contaminated ponds showed an increased fecundity (more eggs) but decreased fertilization rates (fewer hatching tadpoles) as well as lower survival rates and reduced size in Gosner stage 25, suggesting that the higher exposed populations suffer from long-term reproductive impairments. In combination with acute toxicity effects, the detected sublethal effects, which are mostly not addressed in the ecological risk assessment of pesticides, pose a serious threat on amphibian populations in agricultural landscapes.
Interpretation of BRCA2 Splicing Variants: A Case Series of Challenging Variant Interpretations and the Importance of Functional RNA Analysis
Authors: Nix Paola , Mundt Erin , Coffee Bradford , Goossen Elizabeth , Warf Bryan M. , Brown Krystal , Bowles Karla , Roa Benjamin
Published: January 2021

A substantial proportion of pathogenic variants associated with an increased risk of hereditary cancer are sequence variants affecting RNA splicing. The classification of these variants can be complex when both non-functional and functional transcripts are produced from the variant allele. We present four BRCA2 splice site variants with complex variant interpretations (BRCA2 c.68-3T>G, c.68-2A>G, c.425G>T, c.8331+2T>C). Evidence supporting a pathogenic classification is available for each variant, including in silico models, absence in population databases, and published functional data. However, comprehensive RNA analysis showed that some functional transcript may be produced by each variant. BRCA2 c.68-3T>G results in a partial splice defect. For BRCA2 c.68-2A>G and c.425G>T, aberrant splicing was shown to produce a potentially functional, in-frame transcript. BRCA2 c.8331+2T>C may utilize a functional GC donor in place of the wild-type GT donor. The severity of cancer history for carriers of these variants was also assessed using a history weighting algorithm and was not consistent with pathogenic controls (carriers of known pathogenic variants in BRCA2). Due to the conflicting evidence, our laboratory classifies these BRCA2 variants as variants of uncertain significance. This highlights the importance of evaluating new and existing evidence to ensure accurate variant classification and appropriate patient care.
Sustained Attention and Working Memory Predict the Number of Days on Health-Related Benefits in the Year Following Occupational Rehabilitation
Authors: Johansen Thomas , Øyeflaten Irene , Eriksen Hege R. , Lyby Peter S. , Dittrich Winand H. , Holsen Inge , Jakobsen Hanne , Del Risco Kollerud Ruby , Jensen Chris
Published: January 2021

Purpose The objective of this study was to investigate the association between cognitive and emotional functioning and the number of days on health-related benefits such as sick leave, work assessment allowance and disability pension. We investigated whether cognitive and emotional functioning at the start of rehabilitation and the change from the start to the end of rehabilitation predicted the number of days on health-related benefits in the year after occupational rehabilitation. Methods A sample of 317 individuals (age 19–67 years), mainly diagnosed with a musculoskeletal or mental and behavioural ICD-10 disorder, participated. The sample was stratified depending on the benefit status in the year before rehabilitation. Those receiving health-related benefits for the full year comprised the work assessment allowance and disability pension (WAA) group and those receiving benefits for less than a year comprised the sick leave (SL) group. The participants were administered cognitive and emotional computerised tests and work and health questionnaires at the beginning and end of rehabilitation. The cumulative number of days on health-related benefits during 12 months after rehabilitation was the primary outcome variable and age, gender, educational level, subjective health complaints, anxiety, and depression were controlled for in multiple regression analyses. Results The WAA group (n = 179) was significantly impaired at baseline compared to the SL group (n = 135) in focused attention and executive function, and they also scored worse on work and health related variables. Higher baseline scores and change scores from the start to the end of rehabilitation, for sustained attention, were associated with fewer number of health-related benefit days in the WAA group, while higher baseline scores for working memory were associated with fewer number of health-related benefit days in the SL group. Conclusions New knowledge about attention and memory and return to work in individuals with different benefit status may pave the way for more targeted programme interventions. Rehabilitation programmes could benefit from designing interventions that respectively improve sustain attention and working memory related to working life in individuals on sick leave or work assessment allowance and disability pension.
Presupposition, assertion, and definite descriptions
Authors: Elbourne Paul
Published: January 2021

In recent work on the semantics of definite descriptions, some theorists (Elbourne in Definite descriptions, Oxford University Press, Oxford, 2013; Schoubye in Noûs 47(3):496–533, 2013) have advocated broadly Fregean accounts, whereby a definite description ‘theF’ introduces a presupposition to the effect that there is exactly oneFand refers to it if there is, while other theorists (Abbott, in: Gundel, Hedberg (eds) Reference: Interdisciplinary perspectives, Oxford University Press, Oxford, pp. 61–72, 2008; Hawthorne and Manley in The reference book, Oxford University Press, Oxford, 2012) have advocated accounts whereby ‘theF’ introduces a presupposition to the effect that there is exactly oneFbut otherwise has the semantics of ‘anF’, introducing existential quantification. It is argued that the latter theories, since they have definite descriptions encode assertoric content to the effect that there is anF, have difficulty accounting for the felicity of ‘TheFisG’ when it is already presupposed that there is anF.
Socio-economic Drivers of Food Security among Rural Households in Nigeria: Evidence from Smallholder Maize Farmers
Authors: Ogunniyi Adebayo Isaiah , Omotoso Samuel Opeyemi , Salman Kabir Kayode , Omotayo Abiodun Olusola , Olagunju Kehinde Oluseyi , Aremu Adeyemi Oladapo
Published: January 2021

Issues relating to food availability, accessibility/affordability, and food utilization remain paramount among different stakeholders such as policymakers and academics. Using data from 250 maize farming households in Nigeria, the study used Foster–Greer–Thorbecke and probit regression model to investigate the factors determining households food security. The food insecurity measure shows that 23.2% points of the households express the incidence of food insecurity while 5.5% points and 1.8% points were found to have depth and severity of food insecurity, respectively. After controlling for households’ socio-economic and demographic characteristics, the probit regression model suggested that, among others, value of output sold, education, credit access and participation in government safety nets program significantly influenced food security among the maize farmers in the study area. Based on our findings, effort should be intensified to enhance the productivity of land through improved production practices. There should be high-level awareness that will increase farmers’ participation in safety net programs. Thus, government at all levels (local, state, and federal) should have adequate budget allocation to this course in order to improve the livelihood outcomes of the farming households.
Level of the SARS-CoV-2 receptor ACE2 activity is highly elevated in old-aged patients with aortic stenosis: implications for ACE2 as a biomarker for the severity of COVID-19
Authors: Fagyas Miklós , Kertész Attila , Siket Ivetta Mányiné , Bánhegyi Viktor , Kracskó Bertalan , Szegedi Andrea , Szokol Miklós , Vajda Gusztáv , Rácz Ildikó , Gulyás Hajnalka , Szkibák Noémi , Rácz Vivienn , Csanádi Zoltán , Papp Zoltán , Tóth Attila , Sipka Sándor
Published: January 2021

Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin-converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals. About 4 times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (88.3 ± 61.6., n = 111, 20.6 ± 13.4, n = 540, and 16.1 ± 7.4 mU/L, n = 46, respectively). Patients with severe AS were older than patients with hypertension (80 ± 6 years vs. 60 ± 15 years, P < 0.05). Serum ACE2 activity correlated negatively with the left ventricular ejection fraction, aortic root area, TAPSE, and positively with the right ventricular systolic pressure, cardiac diameters in patients with AS. In contrast, circulating ACE2 activity was independent of the blood pressure, peak flow velocity at the aortic root, kidney function (GFR), and inflammatory state (CRP). We found no effect of RAAS inhibitory drugs on the serum ACE2 activity in this group of patients. Our results illustrate circulating ACE2 as a potential interface between chronic inflammation, cardiovascular disease, and COVID-19 susceptibility. Elderly patients with AS have markedly elevated ACE2 levels together with altered left and right ventricular functions, which may pose higher risks during COVID-19. Our clinical data do not support a role for RAAS inhibitors in regulating circulating ACE2 levels.
Mortality Implications of Increased Active Mobility for a Proposed Regional Transportation Emission Cap-and-Invest Program
Authors: Raifman Matthew , Lambert Kathy Fallon , Levy Jonathan I. , Kinney Patrick L.
Published: January 2021

The transportation sector is now the primary contributor to greenhouse gas emissions in the USA. The Transportation Climate Initiative (TCI), a partnership of 12 states and the District of Columbia currently under development, would implement a cap-and-invest program to reduce transportation sector emissions across the Northeast and Mid-Atlantic region, including substantial investment in cycling and pedestrian infrastructure. Using outputs from an investment scenario model and the World Health Organization Health Economic Assessment Tool methodology, we estimate the mortality implications of increased active mobility and their monetized value for three different investment allocation scenarios considered by TCI policymakers. We conduct these analyses for all 378 counties in the TCI region. We find that even for the scenario with the smallest investment in active mobility, when it is fully implemented, TCI would result in hundreds of fewer deaths per year across the region, with monetized benefits in the billions of dollars annually. Under all scenarios considered, the monetized benefits from deaths avoided substantially exceed the direct infrastructure costs of investment. We conclude that investing proceeds in active mobility infrastructure is a cost-effective way of reducing mortality, especially in urban areas, providing a strong motivation for investment in modernization of the transportation system and further evidence of the health co-benefits of climate action.
Dual fluoroscopic imaging and CT-based finite element modelling to estimate forces and stresses of grafts in anatomical single-bundle ACL reconstruction with different femoral tunnels
Authors: Xiao Yang , Ling Ming , Liang Zhenming , Ding Jian , Zhan Shi , Hu Hai , Chen Bin
Published: January 2021

Purpose

Little is known about the in vivo forces and stresses on grafts used in anterior cruciate ligament (ACL) reconstruction. The aims of this study were to evaluate and compare the forces and stresses on grafts used in anatomical single-bundle ACL reconstruction at different locations of the femoral footprint (anterior vs middle vs posterior; high vs middle vs low) during a lunge motion.

Methods

Establish subject-specific finite element models with different graft’s tunnel loci to represent the primary ACL reconstructions. A displacement controlled finite element method was used to simulate lunge motions (full extension to ~ 100° of flexion) with six-degree-of-freedom knee kinematics data obtained from the validated dual fluoroscopic imaging techniques. The reaction force of the femur and maximal principal stresses of the grafts were subsequently calculated during knee flexion.

Results

Increased and decreased graft forces were observed when the grafts were located higher and lower on the femoral footprint, respectively; anterior and posterior graft placement did not significantly affect the graft force. Lower and posterior graft placement resulted in less stress on the graft at higher degrees of flexion; there were no significant differences in stress when the grafts were placed from 0° to 30° of flexion on the femoral footprint.

Conclusion

The proposed method is able to simulate knee joint motion based on in vivo kinematics. The results demonstrate that posterior to the centre of the femoral footprint is the strategic location for graft placement, and this placement results in anatomical graft behaviour with a low stress state.
Species in the wild: a typology of innovation ecosystems
Authors: Klimas Patrycja , Czakon Wojciech
Published: January 2021

The purpose of this paper is to offer a comprehensive and useful typology of innovation ecosystems. While recent conceptual efforts have been allocated to delineating innovation ecosystems from other phenomena, much less systematic attention has been given to the diversity found within the innovation ecosystem realm. We run a thematic analysis of systematic literature reviews and collect 34 specific types of innovation ecosystems. We expand this list with criteria-derived complementary types and propose a set of 50 distinct innovation ecosystem varieties. Next, we identify the 14 typology criteria used so far in the literature, thematically analyse them and aggregate them into a set useful for further rigorous scrutiny and for the incremental collection of empirical findings. Innovation ecosystems can thus be categorized into (1) life cycle, (2) structure, (3) innovation focus, (4) scope of activities, and (5) performance.
Growth of professional noticing of mathematics teachers: a comparative study of Chinese teachers noticing with different teaching experiences
Authors: Yang Xinrong , König Johannes , Kaiser Gabriele
Published: January 2021

The last decade has witnessed increasing interest in the study of teacher noticing in mathematics education research; however, little is known about the growth of teacher noticing and how it is influenced by teaching practice. Departing from the expert-novice-paradigm, in this paper we address this research gap by a cross-sectional study that investigates how Chinese mathematics teachers’ noticing is affected by their developmental stage, measured by the length of their teaching experience. The study included 152 pre-service teachers at the end of their initial teacher education, 162 early career teachers with one to five years’ teaching experience, and 123 experienced mathematics teachers with more than 15 years’ teaching experience, who participated in a video-based assessment of their noticing competency conceptualized by the sub-facets of perception, interpretation, and decision-making. Our findings indicate a nearly linear growth in teacher noticing among Chinese mathematics teachers, with significant differences identified between pre-service and experienced teachers and only small differences between pre-service and early career teachers. Analyses using the method of Differential Item Functioning (DIF) further suggest that pre-service and early career teachers demonstrated strengths in aspects more related to reform-oriented or Westernized approaches to mathematics teaching, such as working with open-ended tasks, identifying characteristics of cooperative learning, and mathematical modeling tasks. By contrast, experienced teachers demonstrated strengths in perceiving students’ thinking, evaluating teachers’ behavior, and analyzing students’ mathematical thinking. Our findings further highlight that the three sub-facets of teacher noticing develop differently within the three participating groups of teachers. These findings suggest that teaching experience acts as one influential factor in the development of teacher noticing in the Chinese context.
Parallelization: the Fourth Leg of Cultural Globalization Theory
Authors: Boman Björn
Published: January 2021

Extending Pieterse’s (1996) tripartite cultural globalization theory consisting of homogenization, hybridization and polarization, the current article outlines a set of exemplifications and justifications of a fourth theoretical underpinning labeled parallelization. The theory implies that at a global scale, crucial events that appear paradoxical or contradictory occur at the same time, such as carbon emissions due to growth-fixated global capitalism, while the causes of carbon emissions lead to greater resilience against the consequences of carbon emissions as wealth accumulates. Other examples discussed are large-scale migration flows which lead to increased segregation in host societies while integration of migrants occur as a parallel process; secularization visa-à-vis the resurgence of religions; clear indications of that the biological component of cognitive abilities decreases due to fertility patterns in many locations around the globe, while the IQ test scores have risen as a consequence of various environmental factors.