bluuebunny/crossref_metadata_2025 huggingface dataset:
NON-EQUILIBRIUM BELOUSOV–ZHABOTINSKY REACTION DESCRIBES THE SPONTANEOUS ACTIVITY OF THE BRAIN
Authors: Zhang Y-idi , Guo Shan , Sun Mingzhu , Tozzi Arturo , Zhao Xin
Published: December 2019

Belousov–Zhabotinsky (BZ) reactions describe chemical patterns in terms of non-equilibrium thermodynamics, chaotic evolution of nonlinear oscillators, excitability under the influence of peculiar chemical stimulations. In touch with this chemical model, we hypothesized that the nonlinear brain electric activity at the edge of the chaos could be triggered by neural oscillation equipped with BZ dynamics, and that changes in neural activity might be correlated with the transient occurrence of (either short and long-range) BZ-like reactions in cortical subareas. To prove our hypothesis of neuronal waves driven by BZ-like processes, we evaluated fMRI movies that assess in vivo BOLD resting state activity of the human brain. We found that the spontaneous activity of the brain display features fully overlapping the recently-introduced local circuits based on BZ chemical reaction. Therefore, neuronal paths during spontaneous activity of the brain match BZ dynamics’ previsions. Our results point towards the brain as crossed by diffusive nonlinear neural oscillations patterns that are predictable. Furthermore, our results suggest that chaotic dynamics arise from nothing else than the network arrangements subtending physical and biological systems.
Gene swamping alters evolution during range expansions in the protist Tetrahymena thermophila
Authors: Moerman Felix , Fronhofer Emanuel A. , Wagner Andreas , Altermatt Florian
Published: December 2019

At species’ range edges, individuals often face novel environmental conditions that may limit range expansion until populations adapt. The potential to adapt depends on genetic variation upon which selection can act. However, populations at species’ range edges are often genetically depauperated. One mechanism to increase genetic variation is to reshuffle existing variation through sex. During range expansions, sex can, however, act as a double-edged sword. The gene swamping hypothesis predicts that for populations expanding along an abiotic gradient, sex can hinder adaptation if asymmetric dispersal leads to numerous maladapted dispersers from the range core swamping the range edge. In this study, we experimentally tested the gene swamping hypothesis by performing replicated range expansions in landscapes with or without an abiotic pH-gradient, using the ciliate Tetrahymena thermophila, while simultaneously manipulating the occurrence of gene flow and sex. We show that sex accelerated evolution of local adaptation in the absence of gene flow, but hindered it in the presence of gene flow. The effect of sex, however, was independent of the pH-gradient, indicating that not only abiotic gradients but also the biotic gradient in population density leads to gene swamping. Overall, our results show that gene swamping can affect adaptation in life-history strategies.
Functional role of Polymerase IV during pollen development inCapsella
Authors: Wang Zhenxing , Butel Nicolas , Santos-González Juan , Borges Filipe , Yi Jun , Martienssen Robert A , Martinez German , Köhler Claudia
Published: December 2019

InArabidopsis thaliana,the DNA-dependent RNA polymerase IV (Pol IV) is required for the formation of transposable element (TE)-derived small RNA (sRNA) transcripts. These transcripts are processed by DICER-LIKE 3 into 24-nt small interfering RNAs (siRNAs) that guide RNA-dependent DNA methylation. In the pollen grain, Pol IV is also required for the accumulation of 21/22-nt epigenetically-activated siRNAs (easiRNAs) that likely silence TEs by post-transcriptional mechanisms. Despite this proposed functional role, loss of Pol IV function inArabidopsisdoes not cause a discernable pollen defect. Here, we show that loss ofNRPD1,encoding the largest subunit of Pol IV in the BrassicaceaeCapsella rubella,causes post-meiotic arrest of pollen development at the microspore stage. As inArabidopsis,all TE-derived siRNAs were depleted inCapsella nrpd1microspores. In wild-type background, we found that the same TEs produced 21/22-nt and 24-nt siRNAs, leading us to propose that Pol IV is generating the direct precursors for 21-24-nt siRNAs, which are targeted by different DICERs. Arrest ofCapsella nrpd1microspores was accompanied by deregulation of genes targeted by Pol IV-dependent siRNAs. The distance of TEs to genes was much closer inCapsella rubellacompared toArabidopsis thaliana,providing a possible explanation for the essential role of Pol IV for pollen development inCapsella.Our study inCapsellauncovers a functional requirement of Pol IV in microspores, emphasizing the relevance of investigating different plant models.

One-sentence summary

Loss of Polymerase IV function inCapsella rubellacauses microspore arrest, revealing an important functional role of Polymerase IV during pollen development.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Claudia Kohler (Claudia.Kohler@slu.se)
Individual differences in successful self-regulation of the dopaminergic midbrain
Authors: Hellrung Lydia , Kirschner Matthias , Sulzer James , Sladky Ronald , Scharnowski Frank , Herdener Marcus , Tobler Philippe N.
Published: December 2019

The dopaminergic midbrain is associated with brain functions, such as reinforcement learning, motivation and decision-making that are often disturbed in neuropsychiatric disease. Previous research has shown that activity in the dopaminergic midbrain can be endogenously modulated via neurofeedback, suggesting potential for non-pharmacological interventions. However, the robustness of endogenous modulation, a requirement for clinical translation, is unclear. Here, we examined how self-modulation capability relates to regulation transfer. Moreover, to elucidate potential mechanisms underlying successful self-regulation, we studied individual prediction error coding, and, during an independent monetary incentive delay (MID) task, individual reward sensitivity. Fifty-nine participants underwent neurofeedback training either in a veridical or inverted feedback group. Successful self-regulation was associated with post-training activity within the cognitive control network and accompanied by decreasing prefrontal prediction error signals and increased prefrontal reward sensitivity in the MID task. The correlative link of dopaminergic self-regulation with individual differences in prefrontal prediction error and reward sensitivity suggests that reinforcement learning contributes to successful self-regulation. Our findings therefore provide new insights in the control of dopaminergic midbrain activity and pave the way to improve neurofeedback training in neuropsychiatric patients.
Uncharacteristic task-evoked pupillary responses implicate atypical locus coeruleus activity in autism
Authors: Granovetter Michael C. , Burlingham Charlie S. , Blauch Nicholas M. , Minshew Nancy J. , Heeger David J. , Behrmann Marlene
Published: December 2019

Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, such as hypersensitivity to environmental stimuli. Attentional engagement is known to be regulated by the locus coeruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether individuals with ASD exhibit a different profile of LC activity compared to typically developing controls under different attentional task demands. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses—an established inverse correlate for baseline LC activity—were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared to controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed only in response to task-relevant and not to task-irrelevant stimuli, providing confirmation that the group differences are specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.

Significance Statement

Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, such as environmental hypersensitivity and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus coeruleus (LC) activity, as the LC has a critical role in attentional modulation. Elevated LC activity is associated with environmental exploration, while moderate LC activity is associated with focused attention on relevant stimuli. This study shows that, under tightly controlled conditions, task-evoked pupil responses—an LC activity proxy—are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.
Novel ankyrin-repeat mutant and modifiers of a kafirin mutant improve sorghum protein digestibility
Authors: Diatta-Holgate Elisabeth , Tuinstra Mitchell , Addo-Quaye Charles , Cisse Ndiaga , Danquah Agyemang , Tongoona Pangirayi , Danquah Eric , Weil Clifford F.
Published: December 2019

Sorghum is a staple food for over 500 million people in Sub-Saharan Africa and Asia, however, sorghum proteins are poorly digested when wet-cooked. Three sorghum mutants were identified in a mutagenized population of the inbred line BTx623 that showed a 23-37% increase in wet-cooked protein digestibility compared to their unmutagenized parent. Furthermore, in comparison to the known high lysine, highly digestible sorghum mutant, P721Q, these mutants had 9% more protein overall that was 10% more digestible, had 12% more lysine, as well as better seed hardness. Using bulked segregant analysis based on whole genome sequencing data, we identified unique genomic regions on chromosome 5 of each EMS mutant that are associated with the increase in protein digestibility. Analyzing shared mutations in candidate genes, the high protein digestibility phenotype in one mutant is linked to a point mutation in a novel, ankyrin repeat protein. In another, the increase is associated with a mutation in a kafirin gene and suggests novel genetic modifiers. This study provides material and molecular markers that can be used to enhance sorghum nutritional value, contribute to fighting malnutrition and elucidate new roles for ankyrin-repeat proteins in plants.

One sentence summary

Mutations in a novel, ankyrin domain protein and genetic modifiers of a known mutation in a seed storage protein lead to increased digestibility of seed proteins in sorghum after wet cooking.
Identification of evolutionarily conserved nuclear matrix proteins and their prokaryotic origins
Authors: Sureka Rahul , Mishra Rakesh
Published: December 2019

Compared to prokaryotic cells, a typical eukaryotic cell is much more complex along with its endomembrane system and membrane-bound organelles. Although the endosymbiosis theories convincingly explain the evolution of membrane-bound organelles such as mitochondria and chloroplasts, very little is understood about the evolutionary origins of the nucleus, the defining feature of eukaryotes. Most studies on nuclear evolution have not been able to take into consideration the underlying structural framework of the nucleus, attributed to the nuclear matrix (NuMat), a ribonucleoproteinaceous structure. This can largely be attributed to the lack of annotation of its core components. Since, NuMat has been shown to provide a structural platform for facilitating a variety of nuclear functions such as replication, transcription, and splicing, it is important to identify its protein components to better understand these processes. In this study, we address this issue using the developing embryos ofD. melanogasterandD. rerioand identify 362 core NuMat proteins that are conserved between the two organisms. We find that of them, 132 protein groups have originated from pre-existing proteins in prokaryotes. While 51 were conserved across all eukaryotic supergroups, 17 new proteins evolved before the evolution of the last eukaryotic common ancestor and together these 68 proteins out of the 362 core conserved NuMat proteins are conserved across all eukaryotes indicating their indispensable nature for nuclear function for over 1.5 billion years of eukaryotic history. Our analysis paves the way to understand the evolution of the complex internal nuclear architecture and its functions.
Quantifying the heterogeneity of macromolecular machines by mass photometry
Authors: Sonn-Segev Adar , Belacic Katarina , Bodrug Tatyana , Young Gavin , VanderLinden Ryan T. , Schulman Brenda A. , Schimpf Johannes , Friedrich Thorsten , Dip Phat Vinh , Schwartz Thomas U. , Bauer Benedikt , Peters Jan-Michael , Struwe Weston B. , Benesch Justin L. P. , Brown Nicholas G. , Haselbach David , Kukura Philipp
Published: December 2019

Sample purity is central to in vitro studies of protein function and regulation, as well as to the efficiency and success of structural studies requiring crystallization or computational alignment of individual molecules. Here, we show that mass photometry (MP) accurately reports on sample heterogeneity using minimal volumes with molecular resolution within minutes. We benchmark our approach by negative stain electron microscopy (nsEM), including workflows involving chemical crosslinking and multi-step purification of a multi-subunit ubiquitin ligase. When applied to proteasome stability, we detect and quantify assemblies invisible to nsEM. Our results illustrate the unique advantages of MP for rapid sample characterization, prioritization and optimization.
Slo2 potassium channel function depends on a SCYL1 protein
Authors: Niu Long-Gang , Liu Ping , Wang Zhao-Wen , Chen Bojun
Published: December 2019

Slo2 potassium channels play important roles in neuronal function, and their mutations in humans cause epilepsies and cognitive defects. However, little is known how Slo2 function is regulated by other proteins. Here we found that the function of C. elegans Slo2 (SLO-2) depends on adr-1, a gene important to RNA editing. However, slo-2 transcripts have no detectable RNA editing events and exhibit similar expression levels in wild type and adr-1 mutants. In contrast, mRNA level of scyl-1, which encodes an orthologue of mammalian SCYL1, is greatly reduced in adr-1 mutants due to deficient RNA editing at a single adenosine in its 3’-UTR. SCYL-1 physically interacts with SLO-2 in neurons. Single-channel open probability of SLO-2 in neurons is reduced by ∼50% in scyl-1 knockout whereas that of human Slo2.2/Slack is doubled by SCYL1 in a heterologous expression system. These results suggest that SCYL-1/SCYL1 is an evolutionarily conserved regulator of Slo2 channels.
Smallholder farmers’ engagement in non-certified organic farming: a case from Southern China
Authors: Zhu Bing , Habisch André
Published: December 2019

Purpose

The purpose of this paper is to investigate the influences of smallholder farmers’ motivations, opportunities and abilities on their satisfactions of non-certified organic farming practices in Southern China based on the motivation–opportunity–ability (MOA) model.

Design/methodology/approach

The sample covers 314 smallholders from Nanning region in Southern China who have engaged in non-certified organic farming. Judgmental and convenient sampling are applied to collect data. Data analysis consists of confirmatory factor analysis, structural equation modelling and mediation test.

Findings

The results show opportunity as dominant impact factor of smallholder farmers’ satisfaction followed by motivation and ability. Also, their commitment to further non-certified organic farming is positively influenced by their satisfactory level. Mediation test reveals that satisfaction partially mediates the relationships between motivation, ability and commitment.

Research limitations/implications

First, due to the limited sample size in a single region, the findings cannot represent even Southern Chinese farmers as an entirety. Second, the study only limited itself in the scope of the MOA model.

Practical implications

Apart from providing updated empirical results for existing studies, this study also highlights the importance of farmer association, supporting scheme as well as the relevant training for the smallholder farmers to size the opportunities, promote their motivations and strengthen their abilities.

Originality/value

As little attention has been given to small-scale farmer who are involved in organic farming practice in China, this paper presents findings based on the MOA framework.
Supply chain quality management and organizational performance
Authors: Hussain Matloub , Khan Mehmood , Ajmal Mian , Ahmad Khan Bilal
Published: December 2019

Purpose

Supply chain quality management (SCQM) has gained less attention in the Arab world, and there is a clear dearth in existing research on this topic, particularly in service organizations. Therefore, the purpose of this paper is to propose a conceptual framework for investigating the impact of SCQM and associated indicators on organizational performance (OP).

Design/methodology/approach

Empirical data have been collected through a survey distributed to a sample of major telecom companies in United Arab Emirates (UAE). To test the conceptual framework, structural equation modeling (SEM) has been used to analyze the data collected from 248 respondents of telecom companies.

Findings

The empirical data showed that SCQM practices are significantly correlated with innovation and operations performance. Statistical analysis through SEM also revealed that customer satisfaction has highest direct impact on OP.

Research limitations/implications

External factors (government regulations, policies and culture) also affect the SCQM practices. Hence, future work should incorporate these parameters as well.

Practical implications

This is a contribution to the continuing research into SCQM, giving supply chain managers and designers a practical way for measuring and implementing SCQM practices across service supply chains.

Originality/value

The contribution of this research, through successive stages of data collection, measurement analysis and refinement, is a set of reliable and valid framework that can be subsequently used in conceptualization and measuring quality of service supply chains.
Ch’ulel Mendoza, un spa diferente: estudio de caso sobre el desarrollo de un nuevo producto en la industria del bienestar
Authors: George Babu , Marano Gina , Henthorne Tony
Published: December 2019

Learning outcomes

Desarrollar un plan de negocios integral para una empresa nueva. Entender el ambiente de negocios. Prepare un análisis DAFO. Desarrollar planes funcionales (de mercadeo, finanzas, recursos humanos, operaciones, etc.). Entender las oportunidades y desafíos del proceso de desarrollo de un nuevo producto.

Case overview/synopsis

Este estudio de caso traza el desarrollo de un plan de negocios para Ch’ulel Mendoza, un complejo de villas ubicado en la Cordillera de los Andes en Argentina, en donde los huéspedes disfrutan de lujosos tratamientos de spa basados en el uso de vino. El plan de negocios debe ser integral, pues se convertirá en la base de un proyecto completamente establecido para posibles inversionistas. Ch’ulel Mendoza está rodeado por los exuberantes viñedos de algunas de las fincas vinícolas más famosas de Argentina. El spa, las instalaciones y los servicios rinden homenaje al patrimonio vitivinícola de la región, promoviendo el vino entre sus huéspedes como algo placentero para consumir y propicio para llevar una vida saludable. El diseño arquitectónico es un guiño directo a la vid: el spa cubierto de tierra es donde los huéspedes absorben los nutrientes curativos de los tratamientos de vinoterapia y de agua, de la misma manera en la que las raíces se nutren de los elementos y el agua provenientes de la tierra; el área del resort aprovecha el espacio al aire libre con terrazas, patios abiertos y piscinas en las que los huéspedes pueden tomar el sol y disfrutar de otros elementos naturales, tal y como lo hacen las plantas de uva. Cuando entre en operación, Ch’ulel Mendoza simbolizará bienestar, recreación y el encanto de la cultura latinoamericana.

Complexity academic level

Nivel de pregrado y posgrado

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 12: Tourism and Hospitality.
La industria chilena del vino: nuevas estrategias internacionales Para 2020
Authors: Felzensztein Christian
Published: December 2019

Learning outcomes

Los estudiantes deben poder realizar un claro análisis competitivo con la información provista en el caso. Los estudiantes también deben desarrollar mapas de posicionamiento, análisis SWOT (debilidades, amenazas, fortalezas y oportunidades), visión, misión, análisis comparativo, segmentación, estrategias de focalización y posicionamiento para mercados internacionales. Los temas de efecto país de origen e imagen de país son relevantes también para el análisis y posicionamiento de los vinos chilenos en mercados internacionales.

Case overview/synopsis

La industria Chilena del vino ha atravesado numerosas y profundas transformaciones en los últimos treinta años. Estas transformaciones han permitido que una nueva generación de talentosos viticultores y vinicultores capitalicen el paraíso vitivinícola de Chile y produzcan vinos de clase mundial. Chile exporta el 70% de su producción vinícola, lo que la convierte en la industria vinícola más globalizada del mundo. A pesar de este éxito innegable, los vinos chilenos enfrentan altos niveles de competencia en los diferentes mercados globales, y sus precios promedio son sustancialmente menores que los de sus competidores. Por consiguiente, los niveles actuales de rentabilidad de la industria son bajos, y existe una urgente necesidad de elevar el posicionamiento premium y los precios promedio para lograr un retorno sostenible en el largo plazo. La industria chilena del vino está preparando un nuevo plan estratégico y una estrategia internacional de mercadeo para 2020, con lineamientos para un vigoroso camino de desarrollo internacional que defina la visión, misión, posicionamiento, objetivos estratégicos, oportunidades y planes de acción de la industria con una nueva perspectiva estratégica de mercadeo. El objetivo de este caso es desarrollar este nuevo plan estratégico y estrategia internacional de mercadeo para la industria vinícola de Chile.

Complexity academic level

MBA y maestría (negocios internacionales, mercadeo, mercadeo internacional).

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 11: Strategy.
Exploration/exploitation innovation and firm performance: the mediation of entrepreneurial orientation and moderation of competitive intensity
Authors: Hou Bojun , Hong Jin , Zhu Ruonan
Published: December 2019

Purpose

Although many scholars have found that exploration and exploitation innovation have significantly positive effects on firm performance, it remains to be resolved whether the relationship between the two is still established at different stages of enterprise development and in different competitive contexts. This paper aims to clarify the effect of exploration/exploitation innovation on firm performance in start-ups, and in particular, the mediation role of entrepreneurial orientation (EO) and the moderation role of competitive intensity are tested to explore their disturbing effects on above relationship.

Design/methodology/approach

The authors construct a theoretical framework to analyze and verify the relationship between innovation, EO and firm performance. The hypotheses of this paper are put forward by theoretical inference. In addition to test the hypotheses, 143 questionnaires are collected from technology-oriented start-ups in Hefei National University Science Park.

Findings

The empirical results show that consistent with previous findings, exploration innovation and exploitation innovation both have positive impact on firm performance; meanwhile, the EO partially mediates the relationship between both innovations and firm performance. What cannot be ignored is that the competition intensity plays a moderation role between EO and firm performance.

Originality/value

The findings reveal that the impact of innovation activities on corporate performance has been disrupted by EO and competition intensity in start-ups. The work of this paper deepens the understanding of the relationship between innovation, EO, external environment and firm performance, which is of guiding significance to the entrepreneurship management of emerging economies.
The relationship between organizational learning capability and business performance
Authors: Pham Lien Thi , Hoang Ha Viet
Published: December 2019

Purpose

The purpose of this paper is to explore the relationship between organizational learning capability and business performance of Vietnamese firms.

Design/methodology/approach

Based on the literature review, the authors proposed five hypotheses covering the relationships between different dimensions of organizational learning capability and business performance. Data collected from a survey of 160 Master of Business Administration students working in different firms in Vietnam were analyzed to test the proposed hypotheses.

Findings

The results confirmed that organizational learning capability has positive effect on business performance. Moreover, two out of four dimensions of organizational learning capability are having positive relationship with business performance (management commitment to learning and “knowledge transfer and integration”).

Practical implications

The paper gives some suggestions for firms to improve their business performance through enhancing organizational learning capability.

Originality/value

This study provides important insights into the recognized yet under-researched relationship between organizational learning capability and business performance and confirms that organizational learning capability has a positive impact on business performance in Vietnam context.
Time‐resolved dual RNA‐seq of tissue uncovers Pseudomonas plecoglossicida key virulence genes in host‐pathogen interaction with Epinephelus coioides
Authors: Luo Gang , Sun Yujia , Huang Lixing , Su Yongquan , Zhao Lingmin , Qin Yingxue , Xu Xiaojin , Yan Qingpi
Published: December 2019

Bacterial pathogen‐host interactions are highly dynamic, regulated processes that have been primarily investigated using in vitro assays. The dynamics of bacterial pathogen‐host interplay in vivo are poorly understood. Using time‐resolved dual RNA‐seq in a Pseudomonas plecoglossicida‐Epinephelus coioides infection model, we observed that bacterial genes encoding classical virulence factors and host genes involved in immune regulation were dynamically expressed during infection. Using network inferencing, we were able to predict interspecies regulatory networks linking bacterial virulence genes to host immune genes. Together with gene co‐expression network analysis of the pathogen, secY was predicted to be a key virulence gene for P. plecoglossicida pathogenicity in the host, fliN was predicted to be a less important virulence gene. The results of bioinformatics prediction were confirmed by animal infection experiments. Our work provides the first paradigm to study dynamic alterations of bacterial pathogen and host interactions based on the elucidation of time‐resolved interactive transcriptomes in vivo, and may be developed into a novel and universal method for revealing the true complexity of the bacterial infection process.
The Association of State Opioid Misuse Prevention Policies With Patient‐ and Provider‐Related Outcomes: A Scoping Review
Authors: MAURI AMANDA I. , TOWNSEND TARLISE N. , HAFFAJEE REBECCA L.
Published: December 2019

Policy Points

This scoping review reveals a growing literature on the effects of certain state opioid misuse prevention policies, but persistent gaps in evidence on other prevalent state policies remain.

Policymakers interested in reducing the volume and dosage of opioids prescribed and dispensed can consider adopting robust prescription drug monitoring programs with mandatory access provisions and drug supply management policies, such as prior authorization policies for high‐risk prescription opioids.

Further research should concentrate on potential unintended consequences of opioid misuse prevention policies, differential policy effects across populations, interventions that have not received sufficient evaluation (eg, Good Samaritan laws, naloxone access laws), and patient‐related outcomes.

Context

In the midst of an opioid crisis in the United States, an influx of state opioid misuse prevention policies has provided new opportunities to generate evidence of policy effectiveness that can inform policy decisions. We conducted a scoping review to synthesize the available evidence on the effectiveness of US state interventions to improve patient and provider outcomes related to opioid misuse and addiction.

Methods

We searched six online databases to identify evaluations of state opioid policies. Eligible studies examined legislative and administrative policy interventions that evaluated (a) prescribing and dispensing, (b) patient behavior, or (c) patient health.

Findings

Seventy‐one articles met our inclusion criteria, including 41 studies published between 2016 and 2018. These articles evaluated nine types of state policies targeting opioid misuse. While prescription drug monitoring programs (PDMPs) have received considerable attention in the literature, far fewer studies addressed other types of state policy. Overall, evidence quality is very low for the majority of policies due to a small number of evaluations. Of interventions that have been the subject of considerable research, promising means of reducing the volume and dosages of opioids prescribed and dispensed include drug supply management policies and robust PDMPs. Due to low study number and quality, evidence is insufficient to draw conclusions regarding interventions targeting patient behavior and health outcomes, including naloxone access laws and Good Samaritan laws.

Conclusions

Recent research has improved the evidence base on several state interventions targeting opioid misuse. Specifically, moderate evidence suggests that drug supply management policies and robust PDMPs reduce opioid prescribing. Despite the increase in rigorous evaluations, evidence remains limited for the majority of policies, particularly those targeting patient health–related outcomes.
Recent advances in heterocyclic aromatic amines: An update on food safety and hazardous control from food processing to dietary intake
Authors: Chen Xiaoqian , Jia Wei , Zhu Li , Mao Lei , Zhang Yu
Published: December 2019

Heterocyclic aromatic amines (HAAs) as probable carcinogenic substances are mainly generated in meat products during thermal processing. Numerous studies have contributed to the analysis, formation, and mitigation of HAAs during food processing. However, few articles have comprehensively reviewed food safety aspects from both food processing and dietary intake regarding the formation, mitigation, metabolism, biomarkers for exposure, hazard control, and risk assessment of HAAs, and related food safety researches. Several factors may influence the generation of HAAs, including processing temperature, processing time, and chemical composition of the meat. Nonetheless, these mutagenic compounds are attenuated to different levels by the addition of natural or synthetic flavorings and antioxidant‐rich marinades, as well as pretreatments using technique such as microwave heating. After dietary intake, different types of HAAs are metabolized in humans by several enzymes, including cytochrome P450s, peroxidases, N‐acetyltransferases, sulfotransferases, uridine diphosphate‐glucuronosyltransferases, and glutathione S‐transferases. Their primary metabolites are further conjugated with DNA or ultimately excreted in urine and feces. The 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine in hair as well as DNA, hemoglobin, and serum albumin adducts has been considered as biomarkers for exposure assessment. Dietary intake information obtained from questionnaires and the results of epidemiological investigations have shown a positive relationship between the intakes of red meat and processed meat and high risk of cancer incidence. As several cancers have been reported to be associated with HAAs, HAAs should be both effectively reduced during food processing and controlled from dietary intake to facilitate human health.
Rapid increase in the prevalence of cannabis use among people with depression in the United States, 2005–17: the role of differentially changing risk perceptions
Authors: Pacek Lauren R. , Weinberger Andrea H. , Zhu Jiaqi , Goodwin Renee D.
Published: December 2019

Aims

To estimate trends in the prevalence of cannabis use and risk perceptions of cannabis use from 2005 to 2017 among United States people with and without depression.

Design

Linear time trends of the prevalence of any, daily and non‐daily past 30‐day cannabis use and perceived great risk associated with regular cannabis use (outcome variables) among people with and without past‐year depression were assessed using logistic regression with survey year as the predictor. All analyses were adjusted for gender, age, race/ethnicity and income; models assessing time trends of cannabis use prevalence were also adjusted for perceived risk.

Setting

The United States: National Survey on Drug Use and Health, an annual cross‐sectional survey, 2005–17 public use data files.

Participants

A total of 728 691 people aged ≥ 12 years.

Measurements

Self‐report of any, daily and non‐daily past 30‐day cannabis use and perceived great risk associated with regular cannabis use.

Findings

The prevalence of any, daily and non‐daily cannabis use in the past month was higher among those with depression versus those without [e.g. 2017 for any use: 18.94 versus 8.67%; adjusted odds ratio (aOR) = 2.17 (95% confidence interval (CI) = 1.92, 2.45)]. Any, daily and non‐daily cannabis use increased among people with and without depression from 2005 to 2017, yet the increase in any (aORs = 1.06 versus 1.05; P = 0.008) and daily (aORs = 1.10 versus 1.07; P = 0.021) cannabis use adjusted for socio‐demographic characteristics was more rapid among those with depression. Perception of great risk associated with regular cannabis use was significantly lower among those with depression (P < 0.001) and decreased significantly more rapidly over the study period among people with depression, compared with those without (aORs = 0.89 versus 0.92; P < 0.001).

Conclusions

The prevalence of cannabis use in the United States increased from 2005 to 2017 among people with and without depression and was approximately twice as common among those with depression. People with depression experienced a more rapid decrease in perception of risk, which may be related to the more rapid increase in any and daily past‐month cannabis use in this group.
Updated guidance for the management of twin and triplet pregnancies from the National Institute for Health and Care Excellence guidance, UK: What's new that may improve perinatal outcomes?
Authors: Gibson Janice L. , Castleman James S. , Meher Shireen , Kilby Mark D.
Published: December 2019

In September 2019, NICE published updated guidance on the management of multiple pregnancy (NG 137). Many of the previous recommendations for care are upheld but there have been important changes: increased frequency of combined ultrasound/specialist antenatal care appointments for pregnancies containing a monochorionic placenta (twins and triplets), increased frequency of ultrasound monitoring in all triplet pregnancies, changes in the definition of selective growth restriction and its subsequent referral pathways, the introduction of some monitoring for twin (or triplet) anemia polycythemia sequence in monochorionic pregnancies (albeit in complex pregnancies or at an advanced stage), and a recommended timing of birth for any pregnancy with monoamniotic fetuses. New recommendations have been made for mode of delivery, fetal monitoring in labor, maternal analgesia, and the prevention of postpartum hemorrhage. The absence of any recommendation relating to the prevention of preterm birth is notable. The basis and implications of the updates that may improve perinatal outcomes are discussed.
The therapeutic efficacy of Bifidobacterium animalis subsp. lactis BB‐12® in infant colic: A randomised, double blind, placebo‐controlled trial
Authors: Nocerino Rita , De Filippis Francesca , Cecere Gaetano , Marino Antonio , Micillo Maria , Di Scala Carmen , de Caro Carmen , Calignano Antonio , Bruno Cristina , Paparo Lorella , Iannicelli Anna M. , Cosenza Linda , Maddalena Ylenia , della Gatta Giusy , Coppola Serena , Carucci Laura , Ercolini Danilo , Berni Canani Roberto
Published: December 2019

Background

The pathogenesis of infant colic is poorly defined. Gut microbiota seems to be involved, supporting the potential therapeutic role of probiotics.

Aims

To assess the rate of infants with a reduction of ≥50% of mean daily crying duration after 28 days of intervention with the probiotic Bifidobacterium animalis subsp. lactis BB‐12® (BB‐12). Secondary outcomes were daily number of crying episodes, sleeping time, number of bowel movements and stool consistency.

Methods

Randomized controlled trial (RCT) on otherwise healthy exclusively breastfed infants with infant colic randomly allocated to receive BB‐12 (1 × 109 CFU/day) or placebo for 28 days. Gut microbiota structure and butyrate, beta‐defensin‐2 (HBD‐2), cathelicidin (LL‐37), secretory IgA (sIgA) and faecal calprotectin levels were assessed.

Results

Eighty infants were randomised, 40/group. The rate of infants with reduction of ≥50% of mean daily crying duration was higher in infants treated with BB‐12, starting from the end of 2nd week. No infant relapsed when treatment was stopped. The mean number of crying episodes decreased in both groups, but with a higher effect in BB‐12 group (−4.7 ± 3.4 vs −2.3 ± 2.2, P < 0.05). Mean daily stool frequency decreased in both groups but the effect was significantly higher in the BB‐12 group; stool consistency was similar between the two groups. An increase in Bifidobacterium abundance (with significant correlation with crying time reduction), butyrate and HBD‐2, LL‐37, sIgA levels associated with a decrease in faecal calprotectin level were observed in the BB‐12 group.

Conclusions

Supplementation with BB‐12 is effective in managing infant colic. The effect could derive from immune and non‐immune mechanisms associated with a modulation of gut microbiota structure and function.
XRF obsidian analysis from Ayacucho Basin in Huamanga province, south‐eastern Peru*
Authors: Giesso M. , Nami H. G. , Capcha J. J. Yataco , Glascock M. D. , Macdonald B. L.
Published: December 2019

Obsidian was broadly used along the Andean Cordillera in South America. Particularly in Peru, its use can be traced to the earliest human occupations, continuously through pre‐Columbian times to contemporary Andean agro‐pastoralist societies. In order to distinguish the provenance of obsidians from Peru, this paper reports a new X‐ray fluorescence (XRF) analysis on several obsidians obtained in surface collections of the Ayacucho region. The analysis and source determination were made by XRF on 52 specimens. The source assignments involved comparisons between the compositional data for the specimens and the University of Missouri Research Reactor (MURR) XRF obsidian database for sources in Peru. After analysing the samples, obsidian sources were recognized and documented. All had small nodules not larger than about 4 cm. They were recovered from Ñahuinpuquio and Marcahuilca hill which belonged to the previously identified Puzolana source. Another identified source was the well‐known Quispisisa, located 120 km south of the city of Ayacucho, and distributed through a vast region in central Peru. The results expand previous observations made on the obsidian provenance at Ayacucho Basin, as well as the extension of the Puzolana source between Yanama and Huarpa hills, south of Ayacucho city.
Sample size and power for the weighted log‐rank test and Kaplan‐Meier based tests with allowance for nonproportional hazards
Authors: Yung Godwin , Liu Yi
Published: December 2019

Asymptotic distributions under alternative hypotheses and their corresponding sample size and power equations are derived for nonparametric test statistics commonly used to compare two survival curves. Test statistics include the weighted log‐rank test and the Wald test for difference in (or ratio of) Kaplan‐Meier survival probability, percentile survival, and restricted mean survival time. Accrual, survival, and loss to follow‐up are allowed to follow any arbitrary continuous distribution. We show that Schoenfeld's equation—often used by practitioners to calculate the required number of events for the unweighted log‐rank test—can be inaccurate even when the proportional hazards (PH) assumption holds. In fact, it can mislead one to believe that 1:1 is the optimal randomization ratio (RR), when actually power can be gained by assigning more patients to the active arm. Meaningful improvements to Schoenfeld's equation are made. The present theory should be useful in designing clinical trials, particularly in immuno‐oncology where nonproportional hazards are frequently encountered. We illustrate the application of our theory with an example exploring optimal RR under PH and a second example examining the impact of delayed treatment effect. A companion R package npsurvSS is available for download on CRAN.
Serial follow‐up of corrected QT interval in Rett syndrome
Authors: Clark Bradley C , Kopp Adam , Morey Wenzhu , Djukic Aleksandra
Published: December 2019

Aim

To identify factors associated with baseline prolonged corrected QT (QTc) and higher risk of QTc prolongation during follow‐up in patients with Rett syndrome (RTT).

Method

A retrospective review of patients receiving an electrocardiogram (ECG) between June 2012 and June 2018 was performed. Age, methyl‐CpG binding protein 2 gene (MECP2) mutation, RTT Severity Scale (RSSS) score, breathing abnormalities, seizure frequency, medications, and ECG parameters were collected. Prolonged QTc was defined as greater than or equal to 460ms. Comparisons at baseline and during follow‐up were made.

Results

In total, 129 unique patients (all female) had 349 ECGs. At baseline, 12 (9.3%) had a prolonged QTc (median 474ms, interquartile range 470–486ms) and were more likely to have moderate/severe breathing abnormalities (66.7% vs 24.8%; p=0.005) and take selective serotonin reuptake inhibitors (SSRIs) (41.7% vs 15.4%; p=0.04). There was no difference in age, RSSS score, seizures, or mutation. Twenty‐six developed prolonged QTc during a median follow‐up of 1 year 7 months (interquartile range 0–3y 6mo). QTc prolongation was associated with p.(Thr158Met) mutation versus the remaining six common mutations (hazard ratio 4.1, 95% confidence interval 1.4–12.0; p=0.01) but not with age, RSSS score, seizures, breathing abnormalities, or SSRIs.

Interpretation

Breathing abnormalities and SSRIs were associated with baseline QTc prolongation and those with p.(Thr158Met) mutation were more likely to develop prolonged QTc over time. Identification of patients with prolonged QTc warrants increased clinical monitoring.

What this paper adds

Breathing abnormalities and selective serotonin reuptake inhibitors are associated with prolonged baseline corrected QT (QTc).

Development of QTc prolongation is associated with the p.(Thr158Met) mutation.
Efficacy and safety of insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Asia Pacific insulin‐naïve people with type 2 diabetes: The EDITION AP randomized controlled trial
Authors: Ji Linong , Kang Eun Seok , Dong XiaoLin , Li Ling , Yuan GuoYue , Shang Shuhua , Niemoeller Elisabeth ,   EDITION AP trial investigators
Published: December 2019

Aim

To compare the efficacy and safety of Gla‐300 versus Gla‐100 in insulin‐naïve people with type 2 diabetes in Asia Pacific.

Materials and Methods

In this open‐label, randomized, active‐controlled, 26‐week study, insulin‐naïve participants with type 2 diabetes inadequately controlled with non‐insulin antihyperglycaemic drugs were randomized (2:1) to Gla‐300 or Gla‐100. The initial daily dose of basal insulin was 0.2 U/kg and was adjusted at least weekly for 8–12 weeks to a target fasting self‐monitored plasma glucose (SMPG) of 4.4–5.6 mmol/L.

Results

Of the 604 participants randomized, 570 (Gla‐300, n = 375; Gla‐100, n = 195) completed the study. Non‐inferiority of Gla‐300 versus Gla‐100 in HbA1c reduction from baseline to week 26 was confirmed. In the Gla‐300 and Gla‐100 groups, 51.1% and 52.2% of participants achieved the HbA1c target of <7.0% (rate ratio [95% CI]: 0.98 [0.84 to 1.14]) and 19.1% and 21.9% achieved the target without hypoglycaemia during the last 12 weeks of treatment (rate ratio [95% CI]: 0.87 [0.63 to 1.20]). Changes in fasting plasma glucose and 24‐hour average eight‐point SMPG were comparable between groups. Incidence of hypoglycaemia at any time of day was similar between treatment groups at week 26, but incidence of any nocturnal hypoglycaemia was numerically lower with Gla‐300 than Gla‐100 over the initial 12‐week titration period and 26‐week on‐treatment period. Rates of adverse events were similar between groups and low for serious adverse events.

Conclusions

Glycaemic control of Gla‐300 is non‐inferior to Gla‐100 with a similar or lower incidence and proportion of hypoglycaemia in people with type 2 diabetes in Asia Pacific, reinforcing the results in the global EDITION programme.
Minimally invasive treatment of an extruded deciduous tooth ‐ Case report
Authors: Faria Laís Veiga , Chaves Hebertt Gonzaga dos Santos , Borges Silva Erlange Andrade , Antunes Leonardo Santos , Antunes Lívia Azeredo Alves
Published: December 2019

When a traumatic dental injury affects the deciduous teeth, the main management is to regularly review the patient until the successor permanent tooth erupts to avoid further consequences to the affected tooth and, especially, sequelae in the tooth germs of the successor permanent tooth. This report describes a case of a tooth extrusion in a 4‐year‐old male treated with a minimally invasive approach. After 4 years of follow‐up, there was a mild disturbance (demarcated opacity in the vestibular surface) and a satisfactory result with normal eruption of the permanent successor tooth.