bluuebunny/crossref_metadata_2025 huggingface dataset:
Compound heterozygous PLA2G6 loss-of-function variants in Swaledale sheep with neuroaxonal dystrophy
Authors: Letko Anna , Strugnell Ben , Häfliger Irene M. , Paris Julia M. , Waine Katie , Drögemüller Cord , Scholes Sandra
Published: November 2020

Sporadic occurrences of neurodegenerative disorders including neuroaxonal dystrophy (NAD) have been previously reported in sheep. However, so far no causative genetic variant has been found for ovine NAD. The aim of this study was to characterize the phenotype and the genetic aetiology of an early-onset neurodegenerative disorder observed in several lambs of purebred Swaledale sheep, a native English breed. Affected lambs showed progressive ataxia and stiff gait and subsequent histopathological analysis revealed the widespread presence of axonal spheroid indicating neuronal degeneration. Thus, the observed clinical phenotype could be explained by a novel form of NAD. After SNP genotyping and subsequent linkage mapping within a paternal half-sib pedigree with a total of five NAD-affected lambs, we identified two loss-of-function variants by whole-genome sequencing in the ovine PLA2G6 gene situated in a NAD-linked genome region on chromosome 3. All cases were carriers of a compound heterozygous splice site variant in intron 2 and a nonsense variant in exon 8. Herein we present evidence for the occurrence of a familial novel form of recessively inherited NAD in sheep due to allelic heterogeneity at PLA2G6. This study reports two pathogenic variants in PLA2G6 causing a novel form of NAD in Swaledale sheep which enables selection against this fatal disorder.
Expression pattern of cochlear microRNAs in the mammalian auditory hindbrain
Authors: Krohs Constanze , Bordeynik-Cohen Mor , Messika-Gold Naama , Elkon Ran , Avraham Karen B. , Nothwang Hans Gerd
Published: November 2020

The auditory system comprises the auditory periphery, engaged in sound transduction and the central auditory system, implicated in auditory information processing and perception. Recently, evidence mounted that the mammalian peripheral and central auditory systems share a number of genes critical for proper development and function. This bears implication for auditory rehabilitation and evolution of the auditory system. To analyze to which extent microRNAs (miRNAs) belong to genes shared between both systems, we characterize the expression pattern of 12 cochlea-abundant miRNAs in the central auditory system. Quantitative real-time PCR (qRT-PCR) demonstrated expression of all 12 genes in the cochlea, the auditory hindbrain and the non-auditory prefrontal cortex (PFC) at embryonic stage (E)16 and postnatal stages (P)0 and P30. Eleven of them showed differences in expression between tissues and nine between the developmental time points. Hierarchical cluster analysis revealed that the temporal expression pattern in the auditory hindbrain was more similar to the PFC than to the cochlea. Spatiotemporal expression analysis by RNA in situ hybridization demonstrated widespread expression throughout the cochlear nucleus complex (CNC) and the superior olivary complex (SOC) during postnatal development. Altogether, our data indicate that miRNAs represent a relevant class of genetic factors functioning across the auditory system. Given the importance of gene regulatory network (GRN) components for development, physiology and evolution, the 12 miRNAs provide promising entry points to gain insights into their molecular underpinnings in the auditory system.
Cross-validation of ultrasound imaging in adolescent idiopathic scoliosis
Authors: de Reuver Steven , Brink Rob C. , Lee Timothy T. Y. , Zheng Yong-Ping , Beek Frederik J. A. , Castelein René M.
Published: November 2020

Purpose

Adolescent idiopathic scoliosis (AIS) patients are exposed to 9–10 times more radiation and a fivefold increased lifetime cancer risk. Radiation-free imaging alternatives are needed. Ultrasound imaging of spinal curvature was shown to be accurate, however, systematically underestimating the Cobb angle. The purpose of this study is to create and cross-validate an equation that calculates the expected Cobb angle using ultrasound spinal measurements of AIS patients.

Methods

Seventy AIS patients with upright radiography and spinal ultrasound were split randomly in a 4:1 ratio to the equation creation (n = 54) or validation (n = 16) group. Ultrasound angles based on the spinous processes shadows were measured automatically by the ultrasound system (Scolioscan, Telefield, Hong Kong). For thoracic and lumbar curves separately, the equation: expected Cobb angle = regression coefficient × ultrasound angle, was created and subsequently cross-validated in the validation group.

Results

Linear regression analysis between ultrasound angles and radiographic Cobb angles (thoracic: R2 = 0.968, lumbar: R2 = 0.923, p < 0.001) in the creation group resulted in the equations: thoracic Cobb angle = 1.43 × ultrasound angle and lumbar Cobb angle = 1.23 × ultrasound angle. With these equations, expected Cobb angles in the validation group were calculated and showed an excellent correlation with the radiographic Cobb angles (thoracic: R2 = 0.959, lumbar: R2 = 0.936, p < 0.001). The mean absolute differences were 6.5°–7.3°. Bland–Altman plots showed good accuracy and no proportional bias.

Conclusion

The equations from ultrasound measurements to Cobb angles were valid and accurate. This supports the implementation of ultrasound imaging, possibly leading to less frequent radiography and reducing ionizing radiation in AIS patients.
A poor appetite or ability to eat and its association with physical function amongst community-dwelling older adults: age, gene/environment susceptibility-Reykjavik study
Authors: Chang Milan , Geirsdottir Olof G. , Launer Lenore J. , Gudnasson Vilmundur , Visser Marjolein , Gunnarsdottir Ingibjorg
Published: November 2020

A poor appetite or ability to eat and its association with physical function have not been explored considerably amongst community-dwelling older adults. The current study examined whether having an illness or physical condition affecting one’s appetite or ability to eat is associated with body composition, muscle strength, or physical function amongst community-dwelling older adults. This is a secondary analysis of cross-sectional data from the age, gene/environment susceptibility-Reykjavik study (n = 5764). Illnesses or physical conditions affecting one’s appetite or ability to eat, activities of daily living, current level of physical activity, and smoking habits were assessed with a questionnaire. Fat mass, fat-free mass, body mass index, knee extension strength, and grip strength were measured, and the 6-m walk test and timed up-and-go test were administered. Individuals who reported illnesses or physical conditions affecting their appetite or ability to eat were considered to have a poor appetite. The associations of appetite or the ability to eat with body composition and physical function were analysed with stepwise linear regression models. A total of 804 (14%) individuals reported having conditions affecting their appetite or ability to eat and had a significantly lower fat-free mass and body mass index, less grip strength, and poorer physical function than did those without any conditions affecting their appetite or ability to eat. Although the factors reported to affect one’s appetite or ability to eat are seldom considered severe, their strong associations with physical function suggest that any condition affecting one’s appetite or ability to eat requires attention.
Light extinction and scattering from aggregates composed of submicron particles
Authors: Cremonesi Llorenç , Minnai Chloé , Ferri Fabio , Parola Alberto , Paroli Bruno , Sanvito Tiziano , Potenza Marco A. C.
Published: November 2020

The influence of the internal structure of inhomogeneous particles on their radiative properties is an open issue repeatedly questioned in many fields of science and technology. The importance of a refined description of the particle composition and structure, going beyond mean-field approximations, is generally recognized. Here, we focus on describing internal inhomogeneities from a statistical point of view. We introduce an analytical description based on the two-point density-density correlation function, or the corresponding static structure factor, to calculate the extinction cross sections. The model agrees with numerical predictions and is validated experimentally with colloidal aggregates in the 0.3–6 μm size range, which serve as an inhomogeneous model system that can be characterized enough to work without any free parameters. The model can be tightly compared to measurements with single particle extinction and scattering and spectrophotometry and suggests a simple behavior for 90° scattering from fractal aggregates as a function of extinction, which is also confirmed experimentally and numerically. We also discuss the case of absorbing particles and report the experimental results for water suspensions of black carbon for both the forward and 90° scattering properties. In this case, the total scattering and the extinction cross sections determine the single scattering albedo, which agrees with numerical simulations. The three parameters necessary to feed radiative transfer models, namely, extinction, asymmetry parameter, and single scattering albedo, can all be set by the analytical model, with explicit dependence on a few parameters. Results are applicable to radiative transfer problems in climate, paleoclimate, star and planetary formation, and nanoparticle optical characterization for science and industry, including the intercomparison of different optical methods such as those adopted by ISO standards.
Pharmaceutical interventions on prescriptions in Norwegian community and hospital pharmacies
Authors: Vik Steinar , Weidemann Pernille , Gangås Ingrid Elisabeth Mehl , Knapstad Stein-Erik , Haavik Svein
Published: November 2020

Background Pharmacists in community and hospital pharmacies assess prescriptions to prevent prescription errors and adverse drug events. There are, however, few reports on prevalence of clinical important pharmaceutical interventions for patients located within primary care. Objective To study documented pharmaceutical interventions on prescriptions in Norwegian pharmacies for patients located in primary care. Setting Data were collected in 11 community pharmacies during a 3 months period in 2016, and the outpatient department of four hospital pharmacies in Norway during a 6 months period of 2018. Method Retrospective analysis of electronically documented pharmaceutical interventions on prescriptions for patients located in primary care. Main outcome measure The number and classification of pharmaceutical interventions in relation to the total number of prescriptions. Results An intervention was documented in 124,178 (45.1%) of the 275,339 prescriptions dispensed during the study period. Interventions of potential clinical importance were performed and documented in 0.8% (2262) of the prescriptions. Conclusion A substantial number of pharmaceutical interventions are performed on prescriptions in Norwegian pharmacies after introduction of electronic prescriptions. A potentially clinical important intervention is performed in one of every 125 prescriptions (0.8%). This result indicates that pharmacists at Norwegian pharmacies prevent more than 400,000 prescription errors of potential clinical importance each year.
Reasoning in Life: Values and Normativity in Georges Canguilhem
Authors: Vissio Gabriele
Published: November 2020

This paper aims at giving an account of the philosophy of norms of Georges Canguilhem in the framework of his philosophical vitalism. According to Canguilhem, vitalism is not a metaphysical or ontological theory, but rather a general attitude or a perspective about life and living beings, both understood employing the axiological concept of ‘normativity’. This notion allows Canguilhem to enlarge the concept of life beyond the field of biological phenomena, encompassing also phenomena of the social world, included technique and scientific knowledge and rationality. Canguilhem’s perspective relocates human activities within a vitalistic conception of life, which redefines the meaning of human reason by putting it in relation to values and norms.
Nitrogen and metal pollution in the southern Caspian Sea: a multiple approach to bioassessment
Authors: Costantini Maria Letizia , Agah Homira , Fiorentino Federico , Irandoost Farnaz , Trujillo Francisco James Leon , Careddu Giulio , Calizza Edoardo , Rossi Loreto
Published: November 2020

The Caspian Sea hosts areas of high ecological value as well as industrial, leisure, and agricultural activities that dump into the water body different kinds of pollutants. In this complex context, a proper description of the origin and potential sources of pollution is necessary to address management and mitigation actions aimed at preserving the quality of the water resource and the integrity of the ecosystems. Here, we aimed at detecting sources of both nitrogen inputs, by N stable isotope analysis of macroalgae, and metals in macroalgae and sediments in two highly anthropized coastal stretches at the Iranian side of the Caspian Sea. Sampling was done near the mouth of rivers and canals draining agricultural and urbanized areas. In the westernmost waters, facing a port city, low macroalgal δ15N signatures indicated industrial fertilizers as the principal source of pollution. By contrast, in the central coastal waters, facing touristic areas, the high macroalgal δ15N indicated N inputs from wastewaters. Here the lowest dissolved oxygen concentrations in waters were associated with excess dissolved inorganic nitrogen. Metal concentrations varied largely in the study areas and were lower in macroalgae than in sediments. Localized peaks of Pb and Zn in sediments were observed in the central coastal sites as probable byproducts of mining activity transported downstream. By contrast, Cr and Ni concentrations were high in all sampling sites, thus potentially representing hazardous elements for marine biota. Overall, macroalgal δ15N coupled with metal analysis in macroalgae and sediments was useful for identifying the main sources of pollution in these highly anthropized coastal areas. This double approach in comprehensive monitoring programs could thus effectively inform stakeholders on major environmental threats, allowing targeted management measures.
ICO investors
Authors: Fahlenbrach Rüdiger , Frattaroli Marc
Published: November 2020

We conduct a detailed analysis of investors in successful initial coin offerings (ICOs). The average ICO has 4700 contributors. The median participant contributes small amounts and many investors sell their tokens before the underlying product is developed. Large presale investors obtain tokens at a discount and flip part of their allocation shortly after the ICO. ICO contributors lack the protections traditionally afforded to investors in early-stage financing. Nevertheless, returns 9 months after the ICO are positive on average, driven mostly by an increase in the value of the Ethereum cryptocurrency.
Advances in percutaneous coronary intervention for chronic total occlusions: current antegrade dissection and reentry techniques and updated algorithm
Authors: Berkhout T. , Claessen B. E. , Dirksen M. T.
Published: November 2020

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) is considered relatively complex with low success rates and high complication rates. Treating a CTO with PCI using the hybrid algorithm increases success rates with acceptable complication rates. An essential part of the hybrid algorithm is antegrade dissection and reentry (ADR). In PCI of a non-CTO coronary lesion, the guidewire over which the stent is advanced and placed stays within the true lumen of the coronary artery. ADR techniques make it possible to cross the lesion through the wall of the coronary artery, the subintimal space, thus creating a small bypass within the architecture of the coronary artery and restoring antegrade blood flow. ADR increases success rates, especially in more difficult CTO procedures. In the last decade, new materials and techniques have been introduced in quick succession, which are summarised in this review. Consequently an updated ADR algorithm is presented, which can support the CTO operator during an ADR procedure.
Entwicklung eines fachspezifischen Kenntnistests zur Erfassung mathematischen Vorwissens von Bewerberinnen und Bewerbern auf ein Mathematik-Lehramtsstudium
Authors: Besser Michael , Göller Robin , Ehmke Timo , Leiss Dominik , Hagena Maike
Published: November 2020

Ausgehend von der Tatsache, dass viele Universitäten bei steigender Zahl an Bewerberinnen und Bewerbern die „richtigen Studierenden“ für ein Lehramtsstudium auswählen müssen und dass diese Auswahl laut einem Urteil des Bundesverfassungsgerichts vom Dezember 2017 nicht allein auf der Hochschulzugangsberechtigungsnote basieren darf, werden belastbare Instrumente zur Unterstützung universitärer Auswahlprozesse benötigt. Mit Blick auf den späteren Studienerfolg besitzen dabei vor allem fachspezifische Kenntnistests eine gute prognostische Validität, für Lehrkräfte gilt Fachwissen hierüber hinaus sogar als Prädiktor für Berufserfolg. Neben symbolischem, formalem und technischem (deklarativem wie prozeduralem) Vorwissen zu mathematischen Inhalten (vor allem der Sekundarstufe I), das in den meisten zu Studienbeginn eingesetzten mathematikspezifischen Kenntnistests operationalisiert wird, wird von Hochschullehrenden jedoch auch Vorwissen in Form prozessbezogener Fähigkeiten im Argumentieren und Beweisen, Problemlösen, Modellieren und Kommunizieren als wesentliche Voraussetzungen für ein erfolgreiches Studium angesehen. Ein empirisch erprobtes Instrument, das derartiges Vorwissen systematisch erfasst und das zur Auswahl von Bewerberinnen und Bewerbern auf ein Mathematik-Lehramtsstudium herangezogen werden kann, liegt jedoch nicht vor. Im Beitrag wird daher die Entwicklung eines fachspezifischen Kenntnistests, der inhalts- und prozessbezogenes mathematisches Vorwissen der Sekundarstufe I operationalisiert, empirisch diskutiert. Zentrale Ergebnisse sind: Schulbezogenes mathematisches Vorwissen zu Inhalten der Sekundarstufe I kann in dieser Breite über hochgradig objektiv auswertbare Aufgaben im Multiple-Choice-Format mittels eines klassischen Paper-Pencil-Tests auch bei Probandinnen und Probanden mit vorhandener Hochschulzugangsberechtigung reliabel und valide erfasst werden. Ein solcher mathematikspezifischer Kenntnistest liefert differenzierte Informationen über mathematisches Wissen, das kaum durch Schulnoten oder allgemeine kognitive Fähigkeiten erfasst wird. Der mathematikspezifische Kenntnistest bietet hierdurch eine ergänzende Grundlage für Zulassungsentscheidungen und hochschuldidaktische Lehrentwicklung.
Microstructure and mechanical properties of short-carbon-fiber/Ti3SiC2 composites
Authors: He Guangqi , Guo Rongxiu , Li Meishuan , Yang Yang , Wang Linshan , Qian Yuhai , Zuo Jun , Xu Jingjun , Liu Changsheng
Published: November 2020

Short-carbon-fibers (Csf) reinforced Ti3SiC2 matrix composites (Csf/Ti3SiC2, the Csf content was 0 vol%, 2 vol%, 5 vol%, and 10 vol%) were fabricated by spark plasma sintering (SPS) using Ti3SiC2 powders and Csf as starting materials at 1300 °C. The effects of Csf addition on the phase compositions, microstructures, and mechanical properties (including hardness, flexural strength (σf), and KIC) of Csf/Ti3SiC2 composites were investigated. The Csf, with bi-layered transition layers, i.e., TiC and SiC layers, were homogeneously distributed in the as-prepared Csf/Ti3SiC2 composites. With the increase of Csf content, the KIC of Csf/Ti3SiC2 composites increased, but the σf decreased, and the Vickers hardness decreased initially and then increased steadily when the Csf content was higher than 2 vol%. These changed performances (hardness, σf, and KIC) could be attributed to the introduction of Csf and the formation of stronger interfacial phases.
Boosting Transport Kinetics of Ions and Electrons Simultaneously by Ti3C2Tx (MXene) Addition for Enhanced Electrochromic Performance
Authors: Wu Wenting , Fang Huajing , Ma Hailong , Wu Liangliang , Zhang Wenqing , Wang Hong
Published: November 2020

Electrochromic technology plays a significant role in energy conservation, while its performance is greatly limited by the transport behavior of ions and electrons. Hence, an electrochromic system with overall excellent performances still need to be explored. Initially motivated by the high ionic and electronic conductivity of transition metal carbide or nitride (MXene), we design a feasible procedure to synthesize the MXene/WO3−x composite electrochromic film. The consequently boosted electrochromic performances prove that the addition of MXene is an effective strategy for simultaneously enhancing electrons and ions transport behavior in electrochromic layer. The MXene/WO3−x electrochromic device exhibits enhanced transmittance modulation and coloration efficiency (60.4%, 69.1 cm2 C−1), higher diffusion coefficient of Li+ and excellent cycling stability (200 cycles) over the pure WO3−x device. Meanwhile, numerical stimulation theoretically explores the mechanism and kinetics of the lithium ion diffusion, and proves the spatial and time distributions of higher Li+ concentration in MXene/WO3−x composite electrochromic layer. Both experiments and theoretical data reveal that the addition of MXene is effective to promote the transport kinetics of ions and electrons simultaneously and thus realizing a high-performance electrochromic device. This work opens new avenues for electrochromic materials design and deepens the study of kinetics mechanism of ion diffusion in electrochromic devices.
Formulations of General Relativity
Authors: Krasnov Kirill
Published: November 2020

This monograph describes the different formulations of Einstein's General Theory of Relativity. Unlike traditional treatments, Cartan's geometry of fibre bundles and differential forms is placed at the forefront, and a detailed review of the relevant differential geometry is presented. Particular emphasis is given to general relativity in 4D space-time, in which the concepts of chirality and self-duality begin to play a key role. Associated chiral formulations are catalogued, and shown to lead to many practical simplifications. The book develops the chiral gravitational perturbation theory, in which the spinor formalism plays a central role. The book also presents in detail the twistor description of gravity, as well as its generalisation based on geometry of 3-forms in seven dimensions. Giving valuable insight into the very nature of gravity, this book joins our highly prestigious Cambridge Monographs in Mathematical Physics series. It will interest graduate students and researchers in the fields of theoretical physics and differential geometry.
Systems of Frequency Distributions for Water and Environmental Engineering
Authors: Singh Vijay P. , Zhang Lan
Published: November 2020

A multitude of processes in hydrology and environmental engineering are either random or entail random components which are characterized by random variables. These variables are described by frequency distributions. This book provides an overview of different systems of frequency distributions, their properties, and applications to the fields of water resources and environmental engineering. A variety of systems are covered, including the Pearson system, Burr system, and systems commonly applied in economics, such as the D'Addario, Dagum, Stoppa, and Esteban systems. The latter chapters focus on the Singh system and the frequency distributions deduced from Bessel functions, maximum entropy theory, and the transformations of random variables. The final chapter introduces the genetic theory of frequency distributions. Using real-world data, this book provides a valuable reference for researchers, graduate students, and professionals interested in frequency analysis.
Trump’s COVID-19 diagnosis and presidential illness
Authors: McDermott Rose
Published: November 2020

President Donald Trump’s COVID-19 illness, and the treatments he received, raise serious concerns about the adequacy of the Twenty-Fifth Amendment to handle cases of transient presidential incapacity. This is particularly challenging when the president refuses to acknowledge any impairment and resists any attempt to constrain his powers, even temporarily.
A short proof that ℬ(L1) is not amenable
Authors: Choi Yemon
Published: November 2020

Non-amenability of ${\mathcal {B}}(E)$ has been surprisingly difficult to prove for the classical Banach spaces, but is now known for E = ℓp and E = Lp for all 1 ⩽ p < ∞. However, the arguments are rather indirect: the proof for L1 goes via non-amenability of $\ell ^\infty ({\mathcal {K}}(\ell _1))$ and a transference principle developed by Daws and Runde (Studia Math., 2010).

In this note, we provide a short proof that ${\mathcal {B}}(L_1)$ and some of its subalgebras are non-amenable, which completely bypasses all of this machinery. Our approach is based on classical properties of the ideal of representable operators on L1, and shows that ${\mathcal {B}}(L_1)$ is not even approximately amenable.
Encoding of a binaural speech stimulus at the brainstem level in middle-aged adults
Authors: Neupane A K , Sinha S K , Gururaj K
Published: November 2020

Objective

Binaural hearing is facilitated by neural interactions in the auditory pathway. Ageing results in impairment of localisation and listening in noisy situations without any significant hearing loss. The present study focused on comparing the binaural encoding of a speech stimulus at the subcortical level in middle-aged versus younger adults, based on speech-evoked auditory brainstem responses.

Methods

Thirty participants (15 young adults and 15 middle-aged adults) with normal hearing sensitivity (less than 15 dB HL) participated in the study. The speech-evoked auditory brainstem response was recorded monaurally and binaurally with a 40-ms /da/ stimulus. Fast Fourier transform analysis was utilised.

Results

An independent sample t-test revealed a significant difference between the two groups in fundamental frequency (F0) amplitude recorded with binaural stimulation.

Conclusion

The present study suggested that ageing results in degradation of F0 encoding, which is essential for the perception of speech in noise.
Charity- and project-based service learning models increase public service motivation outcomes among dietetic students in a community nutrition course
Authors: Dinour Lauren M , Kuscin Jennifer
Published: November 2020

Objective:

To determine whether dietetic students would report a change in their public service motivation (PSM) following a community nutrition service learning (SL) course, and whether the SL model (charity v. project) influences this change differently.

Design:

Using a pretest–posttest, nonequivalent groups quasi-experimental design, this study compared students’ PSM at the beginning and end of a 15-week college-level course. PSM and four component dimensions (attraction to public policy, commitment to public interest, compassion and self-sacrifice) were measured via electronic survey using the PSM scale. Average PSM scores were compared between and within the charity and project groups using independent samples and paired sample t tests, respectively. ANCOVA assessed the effect of SL model on post-survey scores, controlling for pre-survey scores.

Setting:

Public university in northeastern United States.

Participants:

Dietetic students enrolled in six sections of the same undergraduate community nutrition SL course. Students were placed by section in either charity (n 59) or project (n 52) SL experiences and required to complete 14 h in this role.

Results:

Mean PSM total scores increased between pre-survey and post-survey (3·50 v. 3·58; P = 0·001). Students reported small increases in three PSM dimensions: commitment to public interest, compassion and self-sacrifice (all P ≤ 0·01). Holding pre-scores constant, the charity group reported a higher attraction to public policy post-score, while the project group reported a higher self-sacrifice post-score (both P < 0·05).

Conclusions:

Educators should consider adopting SL methods into curricular offerings to enhance students’ motivation for public service.
Epidemics, indigenous communities, and public health in the COVID-19 era: views from smallpox inoculation campaigns in colonial Guatemala
Authors: Few Martha
Published: November 2020

This article explores the tensions between well-intentioned humanitarianism and coercive colonialism during smallpox outbreaks in eighteenth-century Guatemala, when the state extended inoculation programmes to its predominant, culturally diverse Maya communities. Evidence from anti-epidemic campaigns shows public debates broadly comparable to the current COVID-19 crisis: debates about the measurably higher mortality rates for indigenous people and other marginalized groups; debates about the extent of the state’s responsibility for the health of its peoples; and debates on whether or not coercion and violence should be used to ensure compliance with quarantines and public health campaigns. While inoculations provided medical assistance and material help to Maya communities, and resulted in demonstrably lower mortality rates from smallpox, at the same time they functioned as avenues for the expansion of colonial power to intervene in the daily lives of people in those communities, characterized by colonial actors as necessary for their own good, and for the broader public good.
Perspectivizing pandemics: (how) do epidemic histories criss-cross contexts?
Authors: Birn Anne-Emanuelle
Published: November 2020

This article explores a smattering of thematic questions that criss-cross the articles in this special pandemics issue; it signposts some reverberations, overlapping responses, and problematic comparisons currently (mid 2020) being made between past pandemics and the tense experiences (and projections going forward) of COVID-19 across the world. The historical pandemics covered here offer an entry point to a fruitful set of genealogies, chronologies, epidemiologies, trajectories, and imaginaries linked to a host of issues: what makes a pandemic ‘global’? What does a global history perspective bring to the table? How does examining germs and genomes shed light on imperialism as a/the pandemic driver? Where do animals, the environment, and ecology fit in and why are they so often excluded from pandemic histories? What counts as medical humanitarianism when health knowledge, know-how, and cooperation ‘from below’ are sidelined? And what came/comes first: a pandemic or a changed world?
Psychometric Properties of the Measure of Love for Nature
Authors: Pasca Laura , Paniagua David , Aragonés Juan Ignacio
Published: November 2020

Several instruments have been developed to measure the human beings-nature relationship, one of which is the Love and Care for Nature Scale. Three studies were conducted with the aim of analyzing to what extent the construct of love and care for nature, responds to two empirically different dimensions, as well as conducting a psychometric study of the scale. The analysis of construct components showed a large cluster formed by two others (connectedness and well-being), considered “love for nature”, and one two-items cluster referring to “care” (Study 1, n = 51). Considering the “love” items, it was found that ten of the items present adequate psychometric properties (Study 2, n = 1071), and adequate levels of reliability and validity (Study 3, n = 151). Consequently, an appropriate measure of love of nature is established, while an interesting future research line would be to separately study the scale’s two components.
Klassenführung aus Sicht von Schülerinnen und Schülern in der Pflege
Authors: Kohler Verena , Paridon Hiltraut
Published: November 2020

Zusammenfassung. Die Frage, wie eine Klasse zu führen ist, um Lernprozesse angemessen zu gestalten, stellt sich immer wieder neu. Im Laufe der Jahre gab und gibt die Forschung unterschiedliche Antworten auf diese Frage. Doch wie beurteilen Schüler und Schülerinnen Aspekte der Klassenführung und des Lehrerhandels? Erwarten sie eher eine Wissensvermittlung oder eine Begleitung? Wie wichtig sind für sie Regeln? In der vorliegenden Studie wurden Auszubildende aus dem Bereich der Pflege nach ihrer Einschätzung gefragt.
Synchronizing Geomagnetic Field Intensity Records in the Levant Between the 23rd and 15th Centuries BCE: Chronological and Methodological Implications
Authors: Shaar Ron , Bechar Shlomit , Finkelstein Israel , Gallet Yves , Martin Mario A. S. , Ebert Yael , Keinan Jonathan , Gonen Lilach
Published: November 2020

Archeomagnetic records are an important source of information on the past behavior of the geomagnetic field. Frequently, however, coeval archeomagnetic intensity (archeointensity) datasets from nearby locations display significant discrepancies, hampering precise reconstruction of high‐resolution secular variation curve. This is the case for the time interval between the later phase of the Early Bronze and the early phase of the Late Bronze Ages (23rd–15th centuries BCE) in the Levant and Mesopotamia. We address the problem by cross‐correlating archeointensity datasets from four major multilayered archeological sites in the southern Levant (Hazor and Megiddo), northern Levant (Ebla), and western Upper Mesopotamia (Mari). We report new archeointensity data, obtained using the Thellier‐IZZI‐MagIC and the Triaxe methods, from six strata at Hazor and four radiocarbon‐dated strata at Megiddo. From 39 pottery fragments, 199 specimens passed our selection criteria, from which we calculated the mean archeointensity for each stratum. To strengthen the comparison of these data with previously published data from Mari and Ebla, obtained using the Triaxe method, we conducted a blind test of the methods that resulted in indistinguishable results or a difference of less than 1 μT. The synchronized compilation, constrained by radiocarbon data from Megiddo, displays a V‐shaped pattern with a prominent minimum of at least 200 years centered around the 18th century BCE. The study highlights the importance of stacking archeomagnetic data obtained by different archeointensity methods only after cross‐testing the methods and ensuring that archeological samples were dated in a consistent manner.
Uplift Mechanism of the Highest Mountains at Eastern Himalayan Syntaxis Revealed by In Situ Dense Gravimetry
Authors: She Yawen , Fu Guangyu
Published: November 2020

Dense gravity surveys at 408 stations are built around eastern Himalayan syntaxis (EHS). Free‐air gravity anomalies (FGAs) and Bouguer gravity anomalies (BGAs) are obtained based on the in situ data, while the modeled and observed FGAs are merged to increase the accuracy of the gravity anomalies. The variation ranges of FGAs and BGAs are −350–100 and −520 to −320 mGal, respectively. The density structures inversed by the BGAs represent a low‐density zone below the Namche Barwa‐Gyala Peri metamorphic massif. The Moho below the metamorphic massif is significantly shallower than the surrounding areas, and the variation range is between 45 and 75 km. A gravity admittance method is used to study the uplift mechanism of the highest mountains at the EHS. Our result shows that rapid uplift is primarily attributed to the upwelling of the mantle.
Translational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances
Authors: Vorspan Florence , Icick Romain , Mekdad Nawel , Courtin Cindie , Bloch Vanessa , Bellivier Frank , Laplanche Jean-Louis , Prince Nathalie , Pishalin Dmitry , Firmo Cyril , Blugeon Corinne , Mégarbane Bruno , Marie-Claire Cynthia , Benturquia Nadia
Published: November 2020

Motor disturbances strongly increase the burden of cocaine use disorder (CUDs). The objective of our translational study was to identify the genes and biological pathways underlying the tolerance to cocaine-induced motor effects. In a 5-day protocol measuring motor tolerance to cocaine in rats (N = 40), modeling the motor response to cocaine in patients, whole-genome RNA sequencing was conducted on the ventral and dorsal striatum to prioritize a genetic association study in 225 patients with severe CUD who underwent thorough phenotypic (cocaine-induced hyperlocomotion, CIH; and cocaine-induced stereotypies, CIS) and genotypic [571,000 polymorphisms (SNPs)] characterization. We provide a comprehensive description of the rat striatal transcriptomic response to cocaine in our paradigm. Repeated vs. acute cocaine binge administration elicited 27 differentially expressed genes in the ventral striatum and two in the dorsal striatum. One gene, Lrp1b, was differentially expressed in both regions. In patients, LRP1B was significantly associated with both CIS and CIH. CIH was also associated with VPS13A, a gene involved in a severe neurological disorder characterized by hyperkinetic movements. The LRP1B minor allele rs7568970 had a significant protective effect against CIS (558 SNPs, Bonferroni-corrected p = 0.02) that resisted adjustment for confounding factors, including the amount of cocaine use (adjusted beta = −0.965 and −2.35 for heterozygotes and homozygotes, respectively, p < 0.01). Using hypothesis-free prioritization of candidate genes along with thorough methodology in both the preclinical and human analysis pipelines, we provide reliable evidence that LRP1B and VPS13A are involved in the motor tolerance to cocaine in CUD patients, in line with their known pathophysiology.
Alternative splicing landscape of the neural transcriptome in a cytoplasmic-predominant Pten expression murine model of autism-like Behavior
Authors: Thacker Stetson , Sefyi Marilyn , Eng Charis
Published: November 2020

Alternative splicing (AS) is a posttranscriptional mechanism regulating gene expression that complex organisms utilize to expand proteome diversity from a comparatively limited set of genes. Recent research has increasingly associated AS with increased functional complexity in the central nervous systems in higher order mammals. This work has heavily implicated aberrant AS in several neurocognitive and neurodevelopmental disorders, including autism. Due to the strong genetic association between germline PTEN mutations and autism spectrum disorder (ASD), we hypothesized that germline PTEN mutations would alter AS patterns, contributing to the pathophysiology of ASD. In a murine model of constitutional mislocalization of Pten, recapitulating an autism-like phenotype, we found significant changes in AS patterns across the neural transcriptome by analyzing RNA-sequencing data with the program rMATS. A few hundred significant alternative splicing events (ASEs) that differentiate each m3m4 genotype were identified. These ASEs occur in genes enriched in PTEN signaling, inositol metabolism, and several other pathways relevant to the pathophysiology of ASD. In addition, we identified expression changes in several splicing factors known to be enriched in the nervous system. For instance, the master regulator of microexons, Srrm4, has decreased expression, and consequently, we found decreased inclusion of microexons in the Ptenm3m4/m3m4 cortex (~10% decrease). We also demonstrated that the m3m4 mutation disrupts the interaction between Pten and U2af2, a member of the spliceosome. In sum, our observations point to germline Pten disruption changing the landscape of alternative splicing in the brain, and these changes may be relevant to the pathogenesis and/or maintenance of PTEN-ASD phenotypes.
Evidence in cortical folding patterns for prenatal predispositions to hallucinations in schizophrenia
Authors: Rollins Colleen P. E. , Garrison Jane R. , Arribas Maite , Seyedsalehi Aida , Li Zhi , Chan Raymond C. K. , Yang Junwei , Wang Duo , Liò Pietro , Yan Chao , Yi Zheng-hui , Cachia Arnaud , Upthegrove Rachel , Deakin Bill , Simons Jon S. , Murray Graham K. , Suckling John
Published: November 2020

All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear. Sulcal patterns derived from structural magnetic resonance (MR) images can provide a proxy in adulthood for early brain development. We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MR imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS), which have previously been associated with hallucinations in schizophrenia, and constructed cortical folding covariance matrices organized by large-scale functional networks. In both ethnic groups, we demonstrated a significantly shorter left PCS in patients with hallucinations compared to those without, and to healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks. The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins.
Functional validation of CHMP7 as an ADHD risk gene
Authors: Dark Callum , Williams Caitlin , Bellgrove Mark A. , Hawi Ziarih , Bryson-Richardson Robert J.
Published: November 2020

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder of childhood with a strong genetic component. Despite the success of mapping ADHD risk loci, little work has been done to experimentally verify the contribution of these loci to ADHD phenotypes. Meta-analysis of four genome-wide association studies in ADHD suggested CHMP7 as a predisposing gene for ADHD. A DNA variant (rs2294123) mapped to CHMP7 has been shown (via bioinformatic analysis) to have a high likelihood for functionality and correlate with reduced transcript levels. We used CRISPR-Cas9 genome editing to generate a chmp7 zebrafish model for ADHD. chmp7+/− fish showed comparable reductions in mRNA levels to individuals homozygous for the CHMP7 ADHD risk allele. These fish displayed significant hyperactivity over a 24-h period at 6 days post-fertilisation compared to chmp7+/+, but this effect did not persist into juvenile and adulthood stages. In addition, chmp7+/− fish had significantly smaller total brain volumes than chmp7+/+ fish. Finally, the hyperactivity at 6 days post-fertilisation was significantly reduced through the application of methylphenidate, a mainstay pharmacological treatment for ADHD. Overall, this study highlights an important role for CHMP7 in the neurodevelopment of ADHD, and demonstrates the utility of zebrafish for modelling the functional effects of genes conferring risk to ADHD.
PD-L1 degradation pathway and immunotherapy for cancer
Authors: Gou Qian , Dong Chen , Xu Huihui , Khan Bibimaryam , Jin Jianhua , Liu Qian , Shi Juanjuan , Hou Yongzhong
Published: November 2020

Programmed death ligand 1 (PD-L1, CD274) is an essential immune checkpoint protein that binds to programmed death 1 (PD-1) on T-lymphocytes. T cell plays a critical role in killing cancer cells while the cancer cell exhibits immune escape by the expression of PD-L1. The binding of PD-L1 to PD-1 inhibits T cell proliferation and activity, leading to tumor immunosuppression. Increasing evidence shows that PD-L1 protein undergoes degradation in proteasomes or lysosomes by multiple pathways, leading to enhanced immunotherapy for cancer. Although some specific drugs induce PD-L1 degradation and increase antitumor activity, the combination of these drugs with PD-L1/PD-1 blockade significantly enhances cancer immunotherapy. In this review, we have discussed the interaction of PD-L1 degradation with cancer immunotherapy.
Biodegradable, flexible silicon nanomembrane-based NOx gas sensor system with record-high performance for transient environmental monitors and medical implants
Authors: Ko Gwan-Jin , Han Soo Deok , Kim Jeong-Ki , Zhu Jia , Han Won Bae , Chung Jinmook , Yang Seung Min , Cheng Huanyu , Kim Dong-Hwee , Kang Chong-Yun , Hwang Suk-Won
Published: November 2020

A novel transient electronics technology that is capable of completely dissolving or decomposing in certain conditions after a period of operation offers unprecedented opportunities for medical implants, environmental sensors, and other applications. Here, we describe a biodegradable, flexible silicon-based electronic system that detects NO species with a record-breaking sensitivity of 136 Rs (5 ppm, NO2) and 100-fold selectivity for NO species over other substances with a fast response (~30 s) and recovery (~60 s). The exceptional features primarily depend on not only materials, dimensions, and design layouts but also temperatures and electrical operations. Large-scale sensor arrays in a mechanically pliable configuration exhibit negligible deterioration in performance under various modes of applied loads, consistent with mechanics modeling. In vitro evaluations demonstrate the capability and stability of integrated NOx devices in severe wet environments for biomedical applications.
Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides
Authors: Lin Tingzhi , Gu Yuanyun , Qian Pengcheng , Guan Haixing , Walsh Patrick J. , Mao Jianyou
Published: November 2020

The catalytic generation of homoenolates and their higher homologues has been a long-standing challenge. Like the generation of transition metal enolates, which have been used to great affect in synthesis and medicinal chemistries, homoenolates and their higher homologues have much potential, albeit largely unrealized. Herein, a nickel-catalyzed generation of homoenolates, and their higher homologues, via decarbonylation of readily available cyclic anhydrides has been developed. The utility of nickel-bound homoenolates and their higher homologues is demonstrated by cross-coupling with unactivated alkyl bromides, generating a diverse array of aliphatic acids. A broad range of functional groups is tolerated. Preliminary mechanistic studies demonstrate that: (1) oxidative addition of anhydrides by the catalyst is faster than oxidative addition of alkyl bromides; (2) nickel bound metallocycles are involved in this transformation and (3) the catalyst undergoes a single electron transfer (SET) process with the alkyl bromide.