bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of the genera Georthocladius Strenzke, 1941 and Parachaetocladius Wülker, 1959 (Chironomidae, Orthocladiinae): new species descriptions, and keys based on the morphological characters of adult male
Authors: Namayandeh Armin , Moubayed Joel , Ghaderi Edris , Beresford David V.
Published: May 2020

A systematic revision of the genera Georthocladius Strenzke, 1941 and Parachaetocladius Wülker,
1959, and a key to adult males is presented. Two new Holarctic species are diagnosed and described based
on morphological characters of the adult male: Parachaetocladius pyrenaeus sp. n. (Palaearctic region) and
Parachaetocladius broankerothurrie sp. n. (Nearctic region). Additional taxonomic notes on related genera
of Orthocladiinae and synonymies for four species from Japan are also provided, which include:
Parachaetocladius kuramasingularis (Sasa, 1989), Parachaetocladius kamiovatus (Sasa & Hirabayashi, 1993),
and Parachaetocladius sunabaabeus (Tanaka & Sasa, 2001) being the junior synonyms of Parachaetocladius
akanoctavus Sasa & Kamimura, 1987. An updated checklist of both Georthocladius and Parachaetocladius
species with taxonomic remarks, ecology, discussions and a provisional key for adult male are also provided.
Possible Case of Glanders in a Late-Nineteenth- or Early-Twentieth- Century Mennonite Woman in Manitoba, Canada
Authors: Merrett Deborah , Sawatzky Roland , Meiklejohn Christopher
Published: May 2020

This article uses bioarchaeological and biocultural analyses to explore the life history and health status of an older Mennonite woman recovered from an unmarked grave in southeastern Manitoba, dated to the late nine-teenth or early twentieth century. Much of the woman’s skeleton exhibits a number of pathological conditions, including periosteal new bone formation in the lower limbs, healed cranial lesions of the posterior parietals, and lytic lesions in subchondral bone of the elbows, knees, and ankles. In those of the ankles, cloacae exit the metaphyseal bone rather than into the joint capsule. By incorporating macroscopic and radiographic observa¬tions, bone histology, and the medical literature, this study differentiates between the main disease contenders responsible for these bone lesions: tuberculosis, syphilis, and glanders (a zoonotic disease of horses). Given the culturally prescribed construction of housebarns, which placed Mennonite women at substantial risk for zoo¬notic disease exposure, and the historic documentation of severe glanders outbreaks in southeastern Manitoba, this study concludes that glanders is the most plausible diagnosis for the observed skeletal lesions. This is, to our knowledge, the first archaeological demonstration of this disease.

Cet article utilise des analyses bioarchéologiques et bioculturelles pour explorer le cycle de vie et l’état de santé d’une femme Mennonite âgée du sud-est du Manitoba datant de la fin du XIXe ou du début du XXe siècle; l’en¬terrement récupéré d’un cimetière non marqué d’une communauté abandonnée. L’affiliation est établie à partir du lieu d’inhumation et de la tenue vestimentaire, de la construction du cercueil et des sources documentaires.

Une grande partie du squelette présentait une nouvelle formation osseuse sous-périostée, principalement dans les membres inférieurs. De plus, il y avait des lésions crâniennes cicatrisées sur les pariétaux postérieurs et des lésions lytiques dans l’os sous-chondral des genoux et des chevilles avec des cloacae sortant de l’os métaph¬ysaire plutôt que dans la capsule articulaire.

L’étude intègre des observations macroscopiques et radiographiques, l’histologie osseuse, et la littérature médicale pour différencier les principaux candidats: la tuberculose, la syphilis, et la morve (une maladie zoo¬notique des chevaux). La construction des granges-maisons prescrite par la culture a exposé les femmes Men¬nonites à un risque substantiel d’exposition aux maladies zoonotiques, tandis que la documentation historique des épidémies de morve sévères étaye davantage notre diagnostic des lésions squelettiques observées comme les plus plausibles. Il s’agit, à notre connaissance, de la première démonstration archéologique de morve.
CONTRIBUIÇÕES DO ENSINO DE ARTE PARA PREVENÇÃO DA VIOLÊNCIA BULLYING
Authors: Gabriel Gilcimara Juliana , Martins Raul Aragão
Published: May 2020

Violence is an issue that has been discussed in our society due to the degree that it has reached that has brought a series of negative consequences for the entire population. The school as part of this societycould not escape this situation and, although the Ministries of Education and Health advocate preventive educational activities on violence, these are still incipient in the classroom environment. In this perspective, starting from a behavioral approach, the objective of this work is to elaborate, apply and evaluate a set of activities in the discipline of Art, Elementary School I, focused on the prevention of school violence and bullying. The research site was a Municipal School of Elementary Education ina small city in the interior of São Paulo. The research is a quasi-experimental, descriptive and interventional study. The participants were students in the 5th year of elementary school I. The procedures involved the collection of information about the behavior of the students, using the records of the school's occurrence book and elaborating the activities of a teaching program. These activities were designed following the procedures of behavioral theory and trying to meet the characteristics of the behaviors raised in the book of occurrences. The results show that the applied procedure was effective, since the students presented high percentages of correct answers about the knowledge worked and began to recognize the violence with characteristics of bullying. It is considered that this study has brought subsidies for the work of prevention of violence, especially bullying among elementary school children.
EDUCAÇÃO AMBIENTAL, CONSUMO E RESÍDUOS SÓLIDOS: AS CONCEPÇÕES DE PROFESSORAS DE EDUCAÇÃO INFANTIL
Authors: Freita Natália Teixeira Ananias , Marin Fátima Aparecida Dias Gomes
Published: May 2020

The aim of this study was to discuss the formation of teachers and their conceptions and pedagogical practices in relation to Environmental Education in Solid Waste in the context of Early Childhood Education. The methodological notes concern the qualitative approach, of the "case study" type. Ten preschool teachers from the Municipal Schools of Kindergarten were listed as research subjects and the data were obtained through semi-structured interviews. In this article we present the discussions concerning the pedagogical conceptions about Environmental Education, Consumption and Solid Waste mentioned by the preschool teachers. The teachers' conceptions about Environmental Education permeate the bias of Environmental Awareness, linked to the child's relationship with the environment in which they live. Regarding Solid Waste, the teachers connect the theme with recycling. Most teachers understand the distinction between Consumption and Consumerism. We believe that Environmental Education in Solid Waste should be carried out in Early Childhood Education based on daily situations and guided by pedagogical practices appropriate to the children's possibilities of comprehension, which includes a good initial and continuous teacher training on environmental issues.
A ESCOLHA PELO CURSO DE EDUCAÇÃO FÍSICADA UNIFESP
Authors: Terrão Felipe Lopes , Rodrigues Leda Maria de Oliveira
Published: May 2020

Este estudio investigó las razones por la elección del curso de Educación Física de la Universidad Federal de São Paulo.También hace una comparación socioeconómica entre 16 estudiantes del sistema universal o sistema de cuotas. En la segunda etapa, se realizaron cinco entrevistas utilizando los conceptos y los conceptos de Pierre Bourdieu. Las respuestas de los cuestionarios permiten caracterizar a los estudiantes por elsistema universal como clase media y a los estudiantes por el popular sistema de cuotas de perfil. Los análisis de las entrevistas confirmadas la relación entre incorporación en el capital cultural de prácticas corporales de la Educación Física y la elección por el curso. Las declaraciones también muestran que los estudiantes por el sistema universal eligieron Unifesp como estrategia para mantener su posición social. En el caso de los estudiantes por el sistema de cuotas, el acceso a la educación superior pública representa la búsqueda de una nueva reclasificación social.
Laughter, Ethnicity, and Socialist Utopia
Authors: Wang Ban
Published: May 2020

Examining the 1959 film Five Golden Flowers (Wuduo jinhua), this chapter claims that eulogistic comedy propagates the principle of national unity in ethnic diversity by rallying popular passion and joy, and that a new comic aesthetic arose in Mao’s era from an understanding of the dignity of labor.  The new comedy challenges the shopworn dichotomy between the official and unofficial, the ethnic and the national, the lighthearted and the serious. In the 1950s through 1960s, far from being in opposition to the official, the comic is to bridge the gap between ethnic diversity and the emergent nation-state in search of socialist identity in the international arena. Rather than defined by ethnicity and culture, film comedy encourages men and women’s equal participation in socialist labor and the fun-filled ordinary life of love and work. The socialist concept of the Chinese people offers the image of an inclusive world where different ethnic groups can live together and mingle without domination.
Joking after Rebellion
Authors: Wilcox Emily
Published: May 2020

In 1964, the Tibet Military Area Political Department Cultural Work Troupe presented its new dance work, “Laundry Song,” at the PLA’s Third All-Military Arts Festival in Beijing. Although standard accounts interpret “Laundry Song” as a celebration of Han-Tibetan and soldier-civilian harmony, the laughter sparked by some sections of its choreography suggests that multiple layers of meaning existed in this work, one of which stimulated concerns about the continued instability of Tibet in the wake of the 1959 uprising. Using anthropologist Mary Douglas’ theorization of jokes and joke rites, “Laundry Song” can be read as simultaneously disconcerting and comforting. Although it plays into a joke structure present in Maoist society, “Laundry Song” ultimately reinforces dominant ideas and thus is not a joke but a joke rite in Douglas’ terms.
Marrying Islam and Pop Culture
Authors: Barker Thomas
Published: May 2020

As feature film has become mainstream entertainment again, it has coincided with the emergence of new forms of piety and religious practices amongst Indonesian Muslims. Beginning in 2008, a new kind of feature film with Islamic themes began to be made capturing these new modes and ideas of Islamic piety. Tracing the emergence and development of this genre, this chapter looks in depth at how polygamy is represented by culturally progressive filmmakers. To balance normative values around love and gender roles, the films take an anti-polygamy stance by showing the impossibility of polygamous marriage. Behind many Islamic themed films is the director Hanung Bramantyo who has emerged as the most commercially successful but also controversial directors making Islamic films today.
Producing an Oligopoly
Authors: Barker Thomas
Published: May 2020

Even with the entry of new filmmakers, production companies, and investors, the Indonesian film industry remains dominated by an oligopoly of old producers. In identifying this group, this chapter traces their connections back to the 1960s and their consolidation throughout the New Order. With significant presence in television production, these producers are both now wealthy and well-connected, allowing them to reassert themselves in the reformed post-1998 film industry. Largescale capital has been important to the systemisation of film production for the mainstream market but speaks to the legacy structures of the New Order.
Friction: Society, Censorship, and Government Policy
Authors: Barker Thomas
Published: May 2020

Overcoming the regulatory and institutional legacy of the New Order regime has been one of the main ambitions of reformasi. In the film industry, such reform took a back seat to practical efforts film making, resulting in a protracted struggle by filmmakers against censorship and the state agencies responsible for overseeing the film industry. Efforts culminated in the Masyarakat Film Indonesia (MFI) movement which protested the lack of professionalism by returning their Citra Awards before launching a legal challenge to the constitutionality of the Censorship Board in the Constitutional Court. Failing in their bid to abolish censorship, the case precipitated the legislation of a new film law and with it a plethora of new regulations that are adding additional regulatory burdens to filmmakers. In particular, the formation of new representative film bodies complicates the film industry, raising spectres of a return to state over-regulation.
Incubating Loyalty (or Resistance) in Chinese Boarding Schools
Authors: Grose Timothy
Published: May 2020

Chapter One introduces the major institutional hallmarks of the Xinjiang Class. It carefully interrogates the CCP’s current objectives for maintaining boarding schools for Uyghur students. It draws on documents drafted by China’s Ministry of Education, Xinjiang’s Education Department, and individual schools hosting a Xinjiang Class as well as individual testimony to paint a vivid picture of the daily life of Xinjiang Class students. The chapter contends that the primary objective of the Xinjiang Class is to create, from scratch, a cohort of Uyghurs who are loyal to the CCP
Power and Place in Europe in the Early Middle Ages
Authors: Carroll Jayne , Reynolds Andrew , Yorke Barbara
Published: May 2020

This chapter provides an interdisciplinary, scene-setting review of the current state of knowledge in the field of early medieval social complexity and sets out an agenda for future work in this topical area. While much previous work in this field tends to focus on comparisons with the classical world, this contribution emphasises the uniqueness of early medieval modes of social organisation. Introductions are provided to the study of geographies of power through archaeological analyses, vocabularies of power drawing on place-name evidence and notions of law and its enactment at assembly sites from written sources. It is argued that places where power was enacted in a period of non-urban social and administrative complexity must be understood on their own terms. The robusticity and flexibility of early medieval networks of power is also emphasised in the context of a comparative discussion ranging across the European area.
Power, Place and Territory in Early Medieval South-East Wales
Authors: Seaman Andy
Published: May 2020

Wales provides a rare opportunity to explore the development of an early medieval socio-political landscape in a part of the Western Roman Empire that was not subject to Germanic incursion before the 11th century. South-East Wales is particularly important in this respect as it lies within the Romanised zone of lowland Britain. A lack of early evidence, however, has led scholars to construct anachronistic interpretations overly dependent upon evidence drawn from lawbooks of the 13th century. Archaeological evidence and documentary sources from South-East Wales do, however, afford an opportunity to explore the organisation and exploitation of the early medieval landscape independently of the lawbooks. This chapter examines territorial organisation, central places and long-term political continuity in early medieval South-East Wales. It concludes by considering some of the contrasts between patterns of power in South-East Wales and Anglo-Saxon England.
Mints, Moneyers and the Geography of Power in Early Medieval England and its Neighbours
Authors: Naismith Rory
Published: May 2020

Thanks to the inscriptions on early medieval coins, the locations where they were made—mints—are among the best-recorded selections of places in Europe. This chapter seeks to demonstrate that the establishment of mints at particular times and places depended above all on contemporary governmental and social conditions. The later Roman Empire had emphasised the centrality of a few large mints closely tied to the fiscal system, but its successor kingdoms in England, Francia, Italy and Spain followed different criteria. Production was often organised on a more personal than institutional basis through the mediation of moneyers, and commercial activity, administrative functions or military/political significance could all dictate the production of coin. It is essential to consider the interaction of these and other factors in shaping the role of a mint, as well as the diversity in function and scale that could apply within even one territory.
Juan Luis Vives and the Organisation of Patristic Knowledge
Authors: Visser Arnoud
Published: May 2020

The edition of Augustine’s City of God by the Spanish-born humanist Juan Luis Vives (first published in 1522) is one of most successful pieces of patristic scholarship of the sixteenth century. Produced just before the explosive escalation of the Reformation, it remained the key version of the text for over a hundred years. This article analyses the presentation of patristic knowledge in Vives’ commentary to explore how the confessional conflicts affected patristic scholarship. It argues that Vives’ work survived the confessional pressures relatively unscathed because it made Augustine’s work manageable and accessible across confessional parties. In doing so it seeks to highlight the importance of confessional silence in the Republic of Letters as a strategy to confront the pressures of confessionalisation.
Scaliger’s Chronology
Authors: Grafton Anthony
Published: May 2020

Nineteenth-century accounts of Joseph Scaliger’s chronology treated it as a triumph of true over spurious learning. Often, this was equated with a larger triumph of Protestant over Catholic scholarship. A closer look at the nature and reception of Scaliger’s chronology suggests that it formed part of a much more complicated story. Scaliger’s own confessional allegiance, and those of his readers and critics, sometimes shaped their response to sources and issues, but often did not do so. Catholic as well as Protestant scholars provided material for his work, mastered it and subjected it to substantive criticism The mixed reception of his work reflected its technical innovations, and its technical flaws.
MONOLITH IN A HOLLOW: PALEOFUTURISM AND EARTH ART IN STANLEY KUBRICK’S 2001: A SPACE ODYSSEY
Authors: Wamberg Jacob
Published: May 2020

This article analyses 2001 in terms of what I term paleofuturism. Fusing deep future and deep past, this cyclical figure reconciles rational machinic intelligence with diverse repressed temporal layers: archaic cultures, the embryonic state of individuals, and bygone biological and geological eras. In 2001, paleofuturism is nourished by Nietzsche’s Übermensch of the future, reborn as a child, and by Jungian ideas of individuation, the reconciliation with the shadow of the collective unconscious that leads to the black cosmos itself. Further paleofuturist contexts for 2001 are explored in the so-called “ancient astronaut thesis” of science fiction, speculative science, and pseudo-science. Finally, in minimalism and earth art of the late 1960s we meet a structural parallel to 2001’s bypassing of the organic human body, one that bridges the inorganic entropic realities of deep future and deep past.
Georg C.F. Greve
Authors: Albadalejo Carlos , Porta Laura
Published: May 2020

Este número a uno de los asuntos más candentes del panorama mundial en lo referente a cuestiones digitales: la polémica de la propiedad intelectual. Para conseguirlo, hemos entrevistado a cuatro nombres que tienen mucho que decir en este mundo: Cory Doctorow, Fred Von Lohmann, Georg C.F. Greve y Raquel Xalabarder.
Comparison between radiofrequency ablation and sublobar resections for the therapy of stage I non-small cell lung cancer: a meta-analysis
Authors: Chen Shuang , Yang Shize , Xu Shun , Dong Siyuan
Published: May 2020

Background

Sublobar resection (SLR) and radiofrequency ablation (RFA) are the two minimally invasive procedures performed for treating stage I non-small cell lung cancer (NSCLC). This study aimed to compare SLR and RFA for the treatment of stage I NSCLC using the meta-analytical method.

Methods

We searched PubMed and Embase for articles published till December 2019 to evaluate the comparative studies and assess the survival and progression-free survival rates and postoperative complications (PROSPERO registration number: CRD42018087587). A meta-analysis was performed by combining the outcomes of the reported incidences of short-term morbidity and long-term mortality. The fixed or random effects model was utilized to calculate the pooled odds ratios (OR) and the 95% confidence intervals.

Results

Four retrospective studies were considered in the course of this study. The studies included a total of 309 participants; 154 were assigned to the SLR group, and 155 were assigned to the RFA group. Moreover, there were statistically significant differences between the one- and three-year survival rates and one- and three-year progression-free survival rates for the two groups, which were in favor of the SLR group. Among the post-surgical complications, pneumothorax and pleural effusion were more common for the SLR group, while cardiac abnormalities were prevalent in the RFA group. There was no difference in prevalence of hemoptysis between SLR and RFA groups, which might be attributed to the limited study sample size.

Conclusion

Considering the higher survival rates and disease control in the evaluated cases, surgical resection is the preferred treatment method for stage I NSCLC. RFA can be considered a valid alternative in patients not eligible for surgery and in high-risk patients as it is less invasive and requires shorter hospital stay.
Evaluation of the effective dose of amygdalin for the improvement of antioxidant gene expression and suppression of oxidative damage in mice
Authors: Albogami Sarah , Hassan Aziza , Ahmed Nibal , Alnefaie Alaa , Alattas Afnan , Alquthami Lama , Alharbi Afaf
Published: May 2020

Background

Little is known regarding the toxic and therapeutic doses of amygdalin. Treatment regimens and schedules can vary between humans and animal models, and there have been reports of cyanide toxicity due to amygdalin use.

Objective

The aim of this study was to evaluate the effect of different doses of amygdalin on antioxidant gene expression and suppression of oxidative damage in mice.

Methods

Forty adult male mice were divided randomly into four groups (n= 10) as follows and treated orally for two weeks: a control group treated with saline solution, a group treated with amygdalin at 200 mg/kg body weight, a group treated with amygdalin at 100 mg/kg body weight, and a group treated with amygdalin at 50 mg/kg body weight. Liver and testis samples were collected for gene expression, biochemical and histopathological analyses.

Results

The mice treated with medium-dose amygdalin (100 mg/kg) showed upregulated mRNA expression of glutathione peroxidase (P< 0.01) and superoxide dismutase (P< 0.05) and significantly decreased lipid peroxidation (P< 0.05) in hepatic and testicular tissues compared to those in the untreated groups (controls), with mild histopathological effects. The mice treated with high-dose of amygdalin (200 mg/kg) showed downregulated mRNA expression of glutathione peroxidase and superoxide dismutase (P< 0.01) and significantly increased lipid peroxidation (P< 0.05) in both hepatic and testicular tissues compared to those in the untreated groups (controls), with an apparent effect at the histopathological level. No effects were observed in the mice treated with low-dose amygdalin (50 mg/kg) at the gene, protein and histopathological level.

Conclusion

Low-and medium-dose amygdalin did not induce toxicity in the hepatic and testicular tissues of male mice, unlike high-dose amygdalin, which had a negative effect on oxidative balance in mice. Therefore, amygdalin at a moderate dose may improve oxidative balance in mice.
Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions
Authors: Farkas Carlos , Fuentes-Villalobos Francisco , Garrido Jose Luis , Haigh Jody , Barría María Inés
Published: May 2020

Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.
“Zika virus” e desenvolvimento regional: linhas preliminares de análise
Authors: Alves Oliveira Silva José Irivaldo , De Souza Cidoval Morais , Albino Barbosa José Luciano
Published: May 2020

A vida nas cidades tem sido alvo de um processo deletério que está prejudicando, principalmente, as comunidades urbanas e rurais mais vulneráveis. Isso gera instabilidade para a consolidação de um projeto de desenvolvimento regional. Esse panorama tem sido uma tônica no semiárido nordestino. Assim, resolvemos realizar um diagnóstico e analisar os municípios do consórcio intermunicipal São Saruê, localizados no semiárido paraibano. Utilizamos dados secundários e primários, extraídos da observação realizada através das escutatórias, ou seja, de um momento de audição dos atores envolvidos na política pública de saúde, de educação, de meio ambiente e de outros setores que se relacionam com essas. Portanto, esse estudo procura relacionar a presença de arboviroses em municípios com ausência de infraestruturas básicas e a falta de um projeto consistente de desenvolvimento regional.
Os impactos do amianto no município de Minaçu-GO
Authors: Bueno Elielda Aparecida Carvalho , Pietrafesa Pedro Araújo , Bueno Léia Soares
Published: May 2020

O objetivo deste artigo é analisar a dependência econômica do município de Minaçu (Goiás) da produção do amianto. Consideram-se aí os posicionamentos das autoridades municipais e dos responsáveis da mineradora SAMA. Questiona-se o “uso controlado do amianto” defendido com base em argumentos econômicos e mercadológicos a partir de diversos estudos científicos, de diferentes origens, que relacionam o amianto a males à saúde humana. A extração mineral do amianto é a principal fonte econômica do município de Minaçu, localizado na região norte do Estado de Goiás. Desde a sua criação, Minaçu desenvolveu-se em função da mina Cana Brava. Pelo artigo 2º da Lei Federal N. 9.055/1995, era permitida a extração, a industrialização, a comercialização e a distribuição do amianto na variedade crisotila no país. Desde que esse dispositivo foi declarado inconstitucional pelo STF, em 29 de novembro de 2017, Minaçu vive em ambiente de incertezas quanto ao seu futuro.
Stata
Authors: Cox Nicholas J. , Newton H. Joseph
Published: May 2020

Stata is statistical software produced by StataCorp LLC (College Station, TX) and extended and supported by a lively user‐programmer community. It offers both menu support and a command‐line interface and is programmable, in Stata itself, in its own C‐like matrix language Mata, and in other languages. Stata was first released in 1985 and is currently developed through new versions every two years. Stata 16 was released in 2019. Stata is used across many different disciplines, including especially econometrics, applied economics, political science, sociology, biostatistics, medical statistics, and epidemiology.
Combinatorial Testing
Authors: Morgan Joseph
Published: May 2020

Test engineers are often faced with the challenge of selecting test cases that maximize the chance of discovering faults while working within a limited budget. The input space of the system under test (SUT) may be large, or the cost of executing the SUT for each input may be high. In any event, exhaustive testing is usually impossible, and so the engineer is faced with the challenge of sampling from the input space in such a way that the budget is not exceeded and the chance of discovering faults is high. Combinatorial testing is an approach to selecting test cases that seeks to address this challenge. This article introduces readers to the testing approach known ascombinatorial testing.
Cortical atrophy patterns of incident MCI subtypes in the Mayo Clinic Study of Aging
Authors: Machulda Mary M. , Lundt Emily S. , Albertson Sabrina M. , Spychalla Anthony J. , Schwarz Christopher G. , Mielke Michelle M. , Jack Clifford R. , Kremers Walter K. , Vemuri Prashanthi , Knopman David S. , Jones David T. , Bondi Mark W. , Petersen Ronald C.
Published: May 2020

Introduction

We examined differences in cortical thickness in empirically derived mild cognitive impairment (MCI) subtypes in the Mayo Clinic Study of Aging.

Methods

We compared cortical thickness of four incident MCI subtypes (n = 192) to 1257 cognitive unimpaired individuals.

Results

The subtle cognitive impairment cluster had atrophy in the entorhinal and parahippocampal cortex. The amnestic, dysnomic, and dysexecutive clusters also demonstrated entorhinal cortex atrophy as well as thinning in temporal, parietal, and frontal isocortex in somewhat different patterns.

Discussion

We found patterns of atrophy in each of the incident MCI clusters that corresponded to their patterns of cognitive impairment. The identification of MCI subtypes based on cognitive and structural features may allow for more efficient trial and study designs. Given individuals in the subtle cognitive impairment cluster have less structural changes and cognitive decline and may represent the earliest group, this could be a unique group to target with early interventions.
Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal‐Dominant Alzheimer's Disease Colombia Trial
Authors: Rios‐Romenets Silvia , Lopera Francisco , Sink Kaycee M. , Hu Nan , Lian Qinshu , Guthrie Heather , Smith Jillian , Cho William , Mackey Howard , Langbaum Jessica B. , Thomas Ronald G. , Giraldo‐Chica Margarita , Tobon Carlos , Acosta‐Baena Natalia , Muñoz Claudia , Ospina Paula , Tirado Victoria , Henao Eliana , Bocanegra Yamile , Chen Kewei , Su Yi , Goradia Dhruman , Thiyyagura Pradeep , VanGilder Paul S. , Luo Ji , Ghisays Valentina , Lee Wendy , Malek‐Ahmadi Michael H. , Protas Hillary D. , Chen Yinghua , Quiroz Yakeel T. , Reiman Eric M. , Tariot Pierre N. ,   and the API ADAD Colombia Trial Group
Published: May 2020

Introduction

The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo‐controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60‐year‐old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non‐carriers who receive placebo.

Methods

Of the 252 enrolled, we present data on a total of 242 mutation carriers and non‐carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity.

Results

We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non‐carriers, 30 to 53 years of age. Carriers were significantly younger than non‐carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores.

Discussion

Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non‐carriers. Their demographic characteristics are representative of the local population.
TRPV4 Antagonism Prevents Mechanically Induced Myotonia
Authors: Dupont Chris , Novak Kevin , Denman Kirsten , Myers Jessica H. , Sullivan Jeremy M. , Walker Phillip V. , Brown Nicklaus L. , Ladle David R. , Bogdanik Laurent , Lutz Cathleen M. , A. Voss Andrew , Sumner Charlotte J. , Rich Mark M.
Published: May 2020

Objective

Myotonia is caused by involuntary firing of skeletal muscle action potentials and causes debilitating stiffness. Current treatments are insufficiently efficacious and associated with side effects. Myotonia can be triggered by voluntary movement (electrically induced myotonia) or percussion (mechanically induced myotonia). Whether distinct molecular mechanisms underlie these triggers is unknown. Our goal was to identify ion channels involved in mechanically induced myotonia and to evaluate block of the channels involved as a novel approach to therapy.

Methods

We developed a novel system to enable study of mechanically induced myotonia using both genetic and pharmacologic mouse models of myotonia congenita. We extended ex vivo studies of excitability to in vivo studies of muscle stiffness.

Results

As previous work suggests activation of transient receptor potential vanilloid 4 (TRPV4) channels by mechanical stimuli in muscle, we examined the role of this cation channel. Mechanically induced myotonia was markedly suppressed in TRPV4‐null muscles and in muscles treated with TRPV4 small molecule antagonists. The suppression of mechanically induced myotonia occurred without altering intrinsic muscle excitability, such that myotonia triggered by firing of action potentials (electrically induced myotonia) was unaffected. When injected intraperitoneally, TRPV4 antagonists lessened the severity of myotonia in vivo by approximately 80%.

Interpretation

These data demonstrate that there are distinct molecular mechanisms triggering electrically induced and mechanically induced myotonia. Our data indicates that activation of TRPV4 during muscle contraction plays an important role in triggering myotonia in vivo. Elimination of mechanically induced myotonia by TRPV4 inhibition offers a new approach to treating myotonia. ANN NEUROL 2020;88:297–308.
Quantitative Separation of Tremor and Ataxia in Essential Tremor
Authors: Casamento‐Moran Agostina , Yacoubi Basma , Wilkes Bradley J. , Hess Christopher W. , Foote Kelly D. , Okun Michael S. , Wagle Shukla Aparna , Vaillancourt David E. , Christou Evangelos A.
Published: May 2020

Objective

This study addresses an important problem in neurology, distinguishing tremor and ataxia using quantitative methods. Specifically, we aimed to quantitatively separate dysmetria, a cardinal sign of ataxia, from tremor in essential tremor (ET).

Methods

In Experiment 1, we compared 19 participants diagnosed with ET undergoing thalamic deep brain stimulation (DBS; ETDBS) to 19 healthy controls (HC). We quantified tremor during postural tasks using accelerometry and dysmetria with fast, reverse‐at‐target goal‐directed movements. To ensure that endpoint accuracy was unaffected by tremor, we quantified dysmetria in selected trials manifesting a smooth trajectory to the endpoint. Finally, we manipulated tremor amplitude by switching DBS ON and OFF to examine its effect on dysmetria. In Experiment 2, we compared 10 ET participants with 10 HC to determine whether we could identify and distinguish dysmetria from tremor in non‐DBS ET.

Results

Three findings suggest that we can quantify dysmetria independently of tremor in ET. First, ETDBS and ET exhibited greater dysmetria than HC and dysmetria did not correlate with tremor (R2 < 0.01). Second, even for trials with tremor‐free trajectories to the target, ET exhibited greater dysmetria than HC (p < 0.01). Third, activating DBS reduced tremor (p < 0.01) but had no effect on dysmetria (p > 0.2).

Interpretation

We demonstrate that dysmetria can be quantified independently of tremor using fast, reverse‐at‐target goal‐directed movements. These results have important implications for the understanding of ET and other cerebellar and tremor disorders. Future research should examine the neurophysiological mechanisms underlying each symptom and characterize their independent contribution to disability. ANN NEUROL 2020;88:375–387.
Steroid‐Responsive Encephalitis in Coronavirus Disease 2019
Authors: Pilotto Andrea , Odolini Silvia , Masciocchi Stefano , Comelli Agnese , Volonghi Irene , Gazzina Stefano , Nocivelli Sara , Pezzini Alessandro , Focà Emanuele , Caruso Arnaldo , Leonardi Matilde , Pasolini Maria P. , Gasparotti Roberto , Castelli Francesco , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik , Padovani Alessandro
Published: May 2020

Coronavirus disease 2019 (COVID‐19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60‐year‐old patient with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS‐CoV‐2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin‐8 and tumor necrosis factor‐α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high‐dose steroid treatment, thus arguing for an inflammatory‐mediated brain involvement related to COVID‐19. ANN NEUROL 2020;88:423–427.
The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity
Authors: Magliozzi Roberta , Scalfari Antonio , Pisani Anna Isabella , Ziccardi Stefano , Marastoni Damiano , Pizzini Francesca Benedetta , Bajrami Albulena , Tamanti Agnese , Guandalini Maddalena , Bonomi Samuele , Rossi Stefania , Mazziotti Valentina , Castellaro Marco , Montemezzi Stefania , Rasia Sarah , Capra Ruggero , Pitteri Marco , Romualdi Chiara , Reynolds Richard , Calabrese Massimiliano
Published: May 2020

Objective

Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear.

Methods

We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing‐remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated.

Results

Forty‐one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C‐index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (β = 4.7*10−4; p < 0.001), TNF (β = 3.1*10−3; p = 0.004), LIGHT (β = 2.6*10−4; p = 0.003), sCD163 (β = 4.3*10−3; p = 0.009), and TWEAK (β = 3.4*10−3; p = 0.024) were associated with more severe cortical thinning.

Interpretation

A specific CSF profile, mainly characterized by elevated levels of B‐cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562–573
Deletion of JNK Enhances Senescence in Joint Tissues and Increases the Severity of Age‐Related Osteoarthritis in Mice
Authors: Loeser Richard F. , Kelley Kathryn L. , Armstrong Alexandra , Collins John A. , Diekman Brian O. , Carlson Cathy S.
Published: May 2020

Objective

To determine the role of JNK signaling in the development of osteoarthritis (OA) induced by joint injury or aging in mice.

Methods

In the joint injury model, 12‐week‐old wild‐type control, JNK1−/−, JNK2−/−, and JNK1fl/flJNK2−/− aggecan‐CreERT2 double‐knockout mice were subjected to destabilization of the medial meniscus (DMM) (n = 15 mice per group) or sham surgery (n = 9–10 mice per group), and OA was evaluated 8 weeks later. In the aging experiment, wild‐type control, JNK1−/−, and JNK2−/− mice (n = 15 per group) were evaluated at 18 months of age. Mouse knee joints were evaluated by scoring articular cartilage structure, toluidine blue staining, osteophytes, and synovial hyperplasia, by histomorphometric analysis, and by immunostaining for the senescence marker p16INK4a. Production of matrix metalloproteinase 13 (MMP‐13) in cartilage explants in response to fibronectin fragments was measured by enzyme‐linked immunosorbent assay.

Results

There were no differences after DMM surgery between the wild‐type and the JNK‐knockout mouse groups in articular cartilage structure, toluidine blue, or osteophyte scores or in MMP‐13 production in explants. All 3 knockout mouse groups had increased subchondral bone thickness and area of cartilage necrosis compared to wild‐type mice. Aged JNK‐knockout mice had significantly worse articular cartilage structure scores compared to the aged wild‐type control mice (mean ± SD 52 ± 24 in JNK1−/− mice and 60 ± 25 in JNK2−/− mice versus 32 ± 18 in controls; P = 0.02 and P = 0.004, respectively). JNK1−/− mice also had higher osteophyte scores. Deletion of JNK resulted in increased expression of p16INK4a in the synovium and cartilage in older mice.

Conclusion

JNK1 and JNK2 are not required for the development of OA in the mouse DMM model. Deletion of JNK1 or JNK2 is associated with more severe age‐related OA and increased cell senescence, suggesting that JNK may act as a negative regulator of senescence in the joint.
The relationship between premarital counselling and marital harmony among families in Lugari, Kakamega County, Kenya
Authors: Muluhya Keverenge Edward , Kipnusu Robert C. , Tarus Prisca , Karimi Jane
Published: May 2020

Marriage is the most respected institution in the world, and it contributes to the foundations of procreation, leadership and peace and is the hub of economic stability. Currently, there are marital disharmony cases which have led to marriage being viewed with a negative perception. This trend is common in Lugari, Kakamega County, Kenya, resulting in psychological torture, issues with child development in terms of learning and discipline, and a long‐term effect on their behaviour as adults. Premarital counselling was conceived for the purpose of helping families to re‐evaluate their feelings about marriage and its values in order to experience marital harmony. This study sought to determine the relationship between premarital counselling and marital harmony among families. It was guided by solution‐focused theory (SFT). The target population for the study was married couples and premarital counsellors. Purposive and simple random techniques were used to select a representative sample of 20 men, 20 women and 10 premarital counsellors in Lugari, Kakamega County. There was a statistically significant relationship between premarital counselling services and marital harmony among families with a correlation of .893. Therefore, there should be awareness of the existing services, and couples intending to marry should seek premarital counselling interventions and continue to attend counselling after formalising their marriage to keep up with the changing times.
Investigating the gelling behaviour of ‘waxy' paraffinic mixtures during flow shutdown
Authors: Ehsani Sina , Mehrotra Anil K.
Published: May 2020

The flow of waxy or paraffinic crude oils in a pipeline could be shutdown for a variety of reasons, resulting in their cooling and subsequent gelling. Gel formation from a multicomponent wax‐solvent mixture during flow shutdown was investigated experimentally and analyzed with a transient heat‐transfer model based on the moving boundary problem formulation. The gelling experiments were performed with a 0.10 g/g wax‐solvent mixture in a flow‐loop apparatus, following the formation of a steady‐state deposit layer in turbulent flow regime, at two initial wax‐solvent mixture temperatures, with a constant coolant temperature, and for different shutdown times. The gel formation was found to be a fast process, which continued until the gel fully occupied the deposition tube. Gas chromatographic analyses of the deposit samples (under sheared cooling) and the gel samples (under static cooling during flow shutdown) indicated significant differences in the composition and the total wax content. The deposit samples showed an enrichment of heavier paraffins, whereas the composition of gel samples was comparable to that of the original wax‐solvent mixture. The predictions from the transient model showed that a lower initial oil temperature, a lower coolant temperature, and a smaller pipe diameter would result in a faster blockage of the pipe. The predictions from the moving boundary problem formulation agreed well with the flow shutdown data, which further confirmed that the solid and gel formation from wax‐solvent mixtures is modelled satisfactorily as a heat transfer process.
TBHP‐Mediated Oxidative Decarboxylative Cyclization in Water: Direct and Sustainable Access to Anti‐malarial Polycyclic Fused Quinazolinones and Rutaecarpine
Authors: Chen Xingyu , Xia Fei , Zhao Yifan , Ma Ji , Ma Yue , Zhang Dong , Yang Lan , Sun Peng
Published: May 2020

Summary of main observation and conclusion

Polycyclic fused quinazolinones with anti‐malarial activity were synthesized through tert‐butyl hydroperoxide (TBHP)‐mediated oxidative decarboxylative cyclization between commercially available isatins and cyclic amines in one step. The reaction proceeds smoothly in water without additional transition‐metal catalyst, acid and base. The newly synthesized products were evaluated to exhibit moderate to good anti‐malarial activity against chloroquine drug‐sensitive Plasmodium falciparum 3D7 strain. Additionally, this method also provides direct approach to Rutaecarpine in good yield.
Integrated Catalyst of CuZnAl‐Zr and Nb‐HZSM‐5 for One‐Step Synthesis of Aromatics from Syngas
Authors: Xiao Wentao , Li Minzhe , Nawaz Muhammad Asif , Xu Lichong , Song Guiyao , ShuoYang  , Wang Zihao , Liu Dianhua
Published: May 2020

Summary of main observation and conclusion

The addition of Zr increased the dispersion and antisinitering of Cu species and Nb adjusted the HZSM‐5 acidity. Bifunctional catalyst increased selectivity of aromatics to 39.8%, and 60.0% for durene in aromatics. A method for resolving the temperature mismatch between Cu‐based catalysts and HZSM‐5 zeolite is provided.