bluuebunny/crossref_metadata_2025 huggingface dataset:
Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls
Authors: Quattrone Diego , Reininghaus Ulrich , Richards Alex L. , Tripoli Giada , Ferraro Laura , Marino Paolo , Rodriguez Victoria ,   EU-GEI group, Gayer-Anderson Charlotte , Jongsma Hannah E. , Jones Peter B. , La Cascia Caterina , La Barbera Daniele , Tarricone Ilaria , Bonora Elena , Tosato Sarah , Lasalvia Antonio , Szöke Andrei , Arango Celso , Bernardo Miquel , Bobes Julio , Del Ben Cristina Marta , Menezes Paulo Rossi , Llorca Pierre-Michel , Santos Jose Luis , Sanjuán Julio , Tortelli Andrea , Velthorst Eva , de Haan Lieuwe , Rutten Bart P.F. , Lynskey Michael T. , Freeman Tom P. , Kirkbride James B. , Sham Pak C. , O’Donovan Michael C. , Cardno Alastair , Vassos Evangelos , van Os Jim , Morgan Craig , Murray Robin M. , Lewis Cathryn M. , Di Forti Marta
Published: November 2019

Background

Diagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use.

Methods

As part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the associations between these dimensions and schizophrenia (SZ) PRSs, as well as the combined effect of SZ-PRS and cannabis use on the positive symptom/experience dimensions.

Results

SZ-PRS was associated with negative (B=0.18; 95%CI 0.03 to 0.34) and positive (B=0.19; 95%CI 0.03 to 0.36) symptom dimensions in 617 FEP, and with all the psychotic experience dimensions in 979 controls. The putative effect of SZ-PRS on either symptom or experience dimensions was of a small magnitude. Cannabis use was additionally associated with the positive dimensions both in FEP (B=0.31; 95%CI 0.11 to 0.52) and in controls (B=0.26; 95%CI 0.06 to 0.46), independently from SZ-PRS.

Conclusions

We report two validators to the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions, contributing to variation across the psychosis continuum. Findings support the hypothesis that psychotic experiences have similar biological substrates as clinical disorders.
Social and Health Seeking Determinants of Antibiotic Use in Vietnamese Children Under 5: Analysis of National Household Survey Data
Authors: Wang Tianyi , Viet Thanh Le , Son Tung Trinh , van Doorn Rogier , Zheng Charlotte , Makuka Gerald Jamberi , Lewycka Sonia
Published: November 2019

Background

Antibiotic resistance is an important global public health issue, perpetuated by increases in antibiotic use. In low- and middle-income countries (LMICs), tackling antibiotic resistance bacteria is especially challenging. Due to high rates of infectious disease and continuing high mortality from untreated bacterial infections, policy must balance tackling both antibiotic access and antibiotic overuse. This paper investigates the social and health-seeking determinants that impact appropriate and inappropriate antibiotic use in Vietnamese children under 5 for Acute Respiratory Illness (ARI).

Methods

Descriptive analyses and logistic regression models were performed on country-wide household data from UNICEF Multiple Indicator Cluster Surveys in 2006, 2011, 2014.

Results

Results show that antibiotic overuse is higher in those who sought care from a healthcare provider than those who self-treated. In 2014, children who sought care at private facilities and government facilities were more likely to overuse antibiotics for mild respiratory infections (OR 6.1 and OR 3.8 respectively) than those who did not seek care at private and government facilities respectively. Furthermore, higher socioeconomic level was associated with both appropriate antibiotic use for pneumonia and inappropriate for mild ARI. Children in the poorest households in 2011 and 2014 were less likely to appropriately use antibiotics than those from other socioeconomic levels (OR 0.37 and 0.025 respectively). And children in the poorest households in 2014 were less likely to inappropriately use antibiotics for mild ARI than all other socioeconomic levels (OR 0.36).

Conclusions

These findings support, challenge, and broaden current understandings of antibiotic usage in Vietnam. Our results suggest that inappropriate antibiotic use arises from the provider and institutional level. Consequently, we argue that community education efforts and enforcing antibiotics as prescription-only is insufficient. Instead, more focus should be made on reducing financial incentives and infrastructural weaknesses at hospitals and health centres. Furthermore, our results show the need to provide the poorest households with sufficient access to antibiotics. Health policy should tackle the issue of inappropriate use of antibiotics for mild ARI among higher socioeconomic groups.
Quantitative Analysis of Ablation Technique Predicts Arrhythmia Recurrence Following Atrial Fibrillation Ablation
Authors: Jankelson Lior , Dai Matthew , Bernstein Scott , Park David , Holmes Douglas , Aizer Anthony , Chinitz Larry , Barbhaiya Chirag
Published: November 2019

Background

Optimal ablation technique, including catheter-tissue contact during atrial fibrillation (AF) radiofrequency (RF) ablation is associated with improved procedural outcomes. We used a custom developed software to analyze high frequency catheter position data to study the interaction between catheter excursion during lesion placement, lesion-set sequentiality and arrhythmia recurrence.

Methods

100 consecutive patients undergoing first time RF ablation for paroxysmal AF were analyzed. Spatial positioning of the ablation catheter sampled at 60 Hz during RF application was extracted from the CARTO3 system (Biosense Webster Inc., USA) and analyzed using custom developed MATLAB software to determine precise catheter spatial 3D excursion during RF ablation. The primary end point was freedom from atrial arrhythmia lasting longer than 30 seconds after a single ablation procedure.

Results

At one year, 86% of patients were free from recurrent arrhythmia. There was no significant difference in clinical, echocardiographic or ablation characteristics between patients with and without recurrent arrhythmia. Analyzing 15,356,998 position data-points revealed that lesion-set sequentiality and mean lesion catheter excursion were predictors of arrhythmia recurrence. Analyzing arrhythmia recurrence by mean single-lesion catheter excursion (excursion > 2.81mm) and by sequentiality (using 46% of lesions with inter-lesion distance >6mm as cutoff) revealed significantly increased arrhythmia recurrence in the higher excursion group (23% vs. 6%, p=0.03) and in the less sequential group (24% vs. 4%, p=0.02).

Conclusion

Ablation lesion sequentiality measured by catheter inter-lesion distance and catheter stability measured by catheter excursion during lesion placement are potentially modifiable factors affecting arrhythmia recurrence after RF ablation for AF.
The care of older adults with extreme obesity in nursing homes: A collective case study
Authors: Hales Caz , Amankwaa Isaac , Gray Lesley , Rook Helen
Published: November 2019

Objective

To establish the preparedness of nursing homes to deliver high quality, safe and equitable bariatric care for older adults with extreme obesity.

Design and methods

A collective case study approach was used. Data collection included observational and interview data from three nursing homes, and a review of 224,200 resident admissions over a 3-year period in New Zealand.

Participants

Twenty eight health care workers from three nursing homes in the North Island of New Zealand.

Results

Despite a willingness by healthcare staff to care for older adults with extreme obesity, nursing homes were not well equipped to provide safe equitable care for this resident population. Key areas of concern for nursing homes related to limitations in the infrastructure, and financial barriers relating to government funded contracted care services which incorporated equipment procurement and safe staffing ratios.

Conclusion

Nursing homes are unprepared to accommodate the existing and increasing number of older adults with extreme obesity who will require bariatric specific care. Government agencies and policy makers will need to consider the financial implications of the increasing need for bariatric level support within aged care, as well as the impact on individual nursing home resources and quality of care provided. Considerable sector and government attention is needed in relation to infrastructure and funding, to allow for the provision of high quality, safe and equitable care for this population group.
Predicting dengue importation into Europe, using machine learning and model-agnostic methods
Authors: Salami Donald , Sousa Carla Alexandra , Martins Maria do Rosário Oliveira , Capinha César
Published: November 2019

The geographical spread of dengue is a global public health concern. This is largely mediated by the importation of dengue from endemic to non-endemic areas via the increasing connectivity of the global air transport network. The dynamic nature and intrinsic heterogeneity of the air transport network make it challenging to predict dengue importation.

Here, we explore the capabilities of state-of-the-art machine learning algorithms to predict dengue importation. We trained four machine learning classifiers algorithms, using a 6-year historical dengue importation data for 21 countries in Europe and connectivity indices mediating importation and air transport network centrality measures. Predictive performance for the classifiers was evaluated using the area under the receiving operating characteristic curve, sensitivity, and specificity measures. Finally, we applied practical model-agnostic methods, to provide an in-depth explanation of our optimal model’s predictions on a global and local scale.

Our best performing model achieved high predictive accuracy, with an area under the receiver operating characteristic score of 0.94 and a maximized sensitivity score of 0.88. The predictor variables identified as most important were the source country’s dengue incidence rate, population size, and volume of air passengers. Network centrality measures, describing the positioning of European countries within the air travel network, were also influential to the predictions.

We demonstrated the high predictive performance of a machine learning model in predicting dengue importation and the utility of the model-agnostic methods to offer a comprehensive understanding of the reasons behind the predictions. Similar approaches can be utilized in the development of an operational early warning surveillance system for dengue importation.
The significance of microRNA genes expression in ovarian cancer cell lines resistant to cytotoxic drugs
Authors: Kazmierczak Dominika , Jopek Karol , Sterzynska Karolina , Rucinski Marcin , Januchowski Radoslaw
Published: December 2019

Ovarian cancer is the most fatal type of gynecological cancer. The main reason for high mortality is the development of drug resistance. It can be related to increased expression of drug transporters and increased expression of extracellular matrix (ECM) proteins. miRNA is a short noncoding RNA that regulates expression of about 60% of genes in the human genome and plays a crucial role in developing cancer, including resistance to chemotherapy.

Our foremost aim was to exhibit alterations in the miRNA expression levels in the cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), and topotecan (TOP) - resistant variants of W1 sensitive ovarian cancer cell line using miRNA microarray. The second goal was to identify miRNAs responsible for the regulation of drug-resistant genes.

According to our observation, alterations in the expression of 40 miRNA genes. The level of expression of 21 genes was upregulated in at least one drug-resistant cell line. The expression of 19 genes was downregulated in at least one drug-resistant cell line. We identified target genes for 22 miRNAs. Target analysis showed that miRNA regulates key genes responsible for drug resistance. Among others, we observed regulation of the ABCB1 (MDR1) gene in the W1PR1 cell line by miR-363 and regulation of the COL3A1 gene in the W1TR cell line by miR-29a.

Hence, on the basis of our findings, results indicate that genes responsible for drug resistance development in ovarian cancer can be regulated by miRNA.
Enhancer regulation for induced WNT3A expression during neuronal regeneration
Authors: Chang Chu-Yuan , Hung Jui-Hung , Wu Ching-Chih , Liang Min-Zong , Huang Pei-Yuan , Li Joye , Chen Hong-I , Yet Shaw-Fang , Fung Ka Shing , Kao Cheng-Fu , Chen Linyi
Published: December 2019

The treatment of traumatic brain injury (TBI) is limited by a lack of knowledge about the mechanisms underlying neuronal regeneration. WNT family members have been implicated in neurogenesis and aberrant WNT signaling has been associated with neurodegenerative diseases. The current study compared the expression of WNT genes during regeneration of injured cortical neurons. Recombinant WNT3A showed positive effect in promoting neuronal regeneration via in vitro and in vivo TBI models. Intranasal administration of WNT3A protein to TBI mice increased NeuN+ cells compared to control mice as well as retained motor function based on behavior analysis. Since TBI is known to reprogram the epigenome, chromatin immunoprecipitation-sequencing of histone H3K27ac and H3K4me3 was performed to address the transcriptional regulation of WNT3A during neuronal regeneration. We predicted, characterized and proposed that a histone H3K4me1-marked enhancer may undergo topological transformation to regulate the WNT3A gene expression.
Deep learning-based methods for individual recognition in small birds
Authors: Ferreira André C. , Silva Liliana R. , Renna Francesco , Brandl Hanja B. , Renoult Julien P. , Farine Damien R. , Covas Rita , Doutrelant Claire
Published: December 2019

Individual identification is a crucial step to answer many questions in evolutionary biology and is mostly performed by marking animals with tags. Such methods are well established but often make data collection and analyses time consuming and consequently are not suited for collecting very large datasets.

Recent technological and analytical advances, such as deep learning, can help overcome these limitations by automatizing data collection and analysis. Currently one of the bottlenecks preventing the application of deep learning for individual identification is the need of hundreds to thousands of labelled pictures required for training convolutional neural networks (CNNs).

Here, we describe procedures that improve data collection and allow individual identification in captive and wild birds and we apply it to three small bird species, the sociable weaver Philetairus socius, the great tit Parus major and the zebra finch Taeniopygia guttata.

First, we present an automated method that allows the collection of large samples of individually labelled images. Second, we describe how to train a CNN to identify individuals. Third, we illustrate the general applicability of CNN for individual identification in animal studies by showing that the trained CNN can predict the identity of birds from images collected in contexts that differ from the ones originally used to train the CNNs. Fourth, we present a potential solution to solve the issues of new incoming individuals.

Overall our work demonstrates the feasibility of applying state-of-the-art deep learning tools for individual identification of birds, both in the lab and in the wild. These techniques are made possible by our approaches that allow efficient collection of training data. The ability to conduct individual identification of birds without requiring external markers that can be visually identified by human observers represents a major advance over current methods.
Comparing the prioritisation of items and feature-dimensions in visual working memory
Authors: Hajonides Jasper E. , van Ede Freek , Stokes Mark G. , Nobre Anna C.
Published: December 2019

Selective attention can be directed not only to external sensory inputs, but also to internal sensory representations held within visual working memory (VWM). To date, this has been studied predominantly following retrospective cues directing attention to particular items, or their locations in memory. In addition to item-level attentional prioritisation, recent studies have shown that selectively attending to feature dimensions in VWM can also improve memory recall performance. However, no study to date has directly compared item-based and feature-based attention in VWM, nor their neural bases. Here, we compared the benefits of retrospective cues (retro-cues) that were directed either at a multi-feature item or at a feature-dimension that was shared between two spatially segregated items. Behavioural results revealed qualitatively similar attentional benefits in both recall accuracy and response time, but also showed that cueing benefits were larger following item cues. Concurrent EEG measurements further revealed a similar attenuation of posterior alpha oscillations following both item and feature retro-cues when compared to non-informative, neutral retro-cues. We argue that attention can act flexibly to prioritise the most relevant information – at either the item or the feature-level – to optimise ensuing memory-based task performance, and we discuss the implications of the observed commonalities and differences between item-level and feature-level prioritisation in VWM.
A yeast platform for high-level synthesis of natural and unnatural tetrahydroisoquinoline alkaloids
Authors: Pyne Michael E. , Kevvai Kaspar , Grewal Parbir S. , Narcross Lauren , Choi Brian , Bourgeois Leanne , Dueber John E. , Martin Vincent J. J.
Published: December 2019

The tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogues. The plant kingdom manufactures more than 3,000 THIQ alkaloids, including the opioids morphine and codeine. While microbial species have been engineered to synthesize a few compounds from the benzylisoquinoline alkaloid (BIA) family of THIQs, low product titers impede industrial viability and limit access to the full chemical space. Here we report a THIQ platform by increasing yeast production of the central BIA intermediate (S)-reticuline to more than 3 g L-1, a 38,000-fold improvement over our first-generation strain. Gains in BIA output coincided with the formation of several substituted THIQs derived from host amino acid catabolism. Enabled by this activity, we repurposed the yeast Ehrlich pathway and demonstrate the synthesis of an array of unnatural THIQ scaffolds. This work provides a blueprint for synthesizing new privileged structures and will enable the targeted overproduction of thousands of THIQ products, including natural and semi-synthetic opioids.
Efficient Homology-directed Repair with Circular ssDNA Donors
Authors: Iyer Sukanya , Mir Aamir , Vega-Badillo Joel , Roscoe Benjamin P. , Ibraheim Raed , Zhu Lihua Julie , Lee Jooyoung , Liu Pengpeng , Luk Kevin , Mintzer Esther , Soares de Brito Josias , Zamore Philip D. , Sontheimer Erik J. , Wolfe Scot A.
Published: December 2019

While genome editing has been revolutionized by the advent of CRISPR-based nucleases, difficulties in achieving efficient, nuclease-mediated, homology-directed repair (HDR) still limit many applications. Commonly used DNA donors such as plasmids suffer from low HDR efficiencies in many cell types, as well as integration at unintended sites. In contrast, single-stranded DNA (ssDNA) donors can produce efficient HDR with minimal off-target integration. Here, we describe the use of ssDNA phage to efficiently and inexpensively produce long circular ssDNA (cssDNA) donors. These cssDNA donors serve as efficient HDR templates when used with Cas9 or Cas12a, with integration frequencies superior to linear ssDNA (lssDNA) donors. To evaluate the relative efficiencies of imprecise and precise repair for a suite of different Cas9 or Cas12a nucleases, we have developed a modified Traffic Light Reporter (TLR) system [TLR-Multi-Cas Variant 1 (MCV1)] that permits side-by-side comparisons of different nuclease systems. We used this system to assess editing and HDR efficiencies of different nuclease platforms with distinct DNA donor types. We then extended the analysis of DNA donor types to evaluate efficiencies of fluorescent tag knock-ins at endogenous sites in HEK293T and K562 cells. Our results show that cssDNA templates produce efficient and robust insertion of reporter tags. Targeting efficiency is high, allowing production of biallelic integrants using cssDNA donors. cssDNA donors also outcompete lssDNA donors in template-driven repair at the target site. These data demonstrate that circular donors provide an efficient, cost-effective method to achieve knock-ins in mammalian cell lines.
Role of post-trial visual feedback on unintentional force drift during isometric finger force production tasks
Authors: Balamurugan S , Rachaveti Dhanush , SKM Varadhan
Published: December 2019

Force produced during an isometric finger force production task tends to drift towards a lower magnitude when visual information is occluded. This phenomenon of drift in force without one’s awareness is called unintentional drift. The present study used epilogue, a particular case of post-trial visual feedback, and compared the unintentional drift for two conditions, i.e., with and without the epilogue. For this purpose, fourteen healthy participants were recruited for the experiments and were instructed to produce fingertip forces using four fingers of the right hand with the target line at 15% MVC. A trial lasted for sixteen seconds, where for the initial eight seconds, there is visual feedback followed by the visual occlusion period. The results showed a significant reduction in unintentional drift for the condition involving epilogue when compared to no epilogue. This reduction in drift is due to the shift in the referent configuration parameter by the phenomenon of RC back coupling. Further, we also claim that there might be a distribution of λs or RCs, based on the history of tuning of the control parameter by the central controller. This distribution of λs selected by the central controller in a redundant environment based on the epilogue resulted in a reduction of unintentional drift.
Trans-acting role of the leader peptide peTrpL in posttranscriptional regulation of multiresistance
Authors: Melior Hendrik , Li Siqi , Förstner Konrad U. , Azarderakhsh Saina , Barth-Weber Susanne , Evguenieva-Hackenberg Elena
Published: December 2019

Bacterial ribosome-dependent attenuators are widespread posttranscriptional regulators. They harbour small upstream ORFs (uORFs) encoding leader peptides, for which no functions in trans are known yet. In the soil-dwelling plant symbiont Sinorhizobium meliloti, the tryptophan biosynthesis gene trpE(G) is preceded by the uORF trpL and is regulated by transcription attenuation according to tryptophan availability. However, trpLE(G) transcription is initiated independently of the tryptophan level in the cell, thereby ensuring a largely tryptophan-independent production of the leader peptide peTrpL. We provide evidence that peTrpL plays a role in the differential posttranscriptional regulation of the smeABR operon encoding the major multidrug efflux pump SmeAB and the TtgR-type transcription repressor SmeR. We show that peTrpL is involved in a tetracycline-dependent smeR mRNA destabilization and forms an antibiotic-dependent ribonucleoprotein (ARNP) complex with smeR and its antisense RNA (asRNA). Induction of asRNA transcription, ARNP formation and smeR downregulation were promoted by several antibiotics and the flavonoid genistein, and the resistance to these antimicrobial compounds was increased by peTrpL. The role of peTrpL in resistance is conserved in other soil Alphaproteobacteria.
BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity
Authors: Bittner Zsófia A. , Liu Xiao , Shankar Sangeetha , Tapia-Abellán Ana , Kalbacher Hubert , Andreeva Liudmila , Mangan Matthew , Düwell Peter , Lovotti Marta , Bosch Karlotta , Dickhöfer Sabine , Marcu Ana , Stevanović Stefan , Herster Franziska , Löffler Markus W. , Wolz Olaf-Oliver , Schilling Nadine A. , Kümmerle-Deschner Jasmin , Wagner Samuel , Delor Anita , Grimbacher Bodo , Wu Hao , Latz Eicke , Weber Alexander N. R.
Published: December 2019

Activity of the NLRP3 inflammasome, a critical mediator of inflammation (1), is controlled by accessory proteins (2, 3), post-translational modifications (4, 5), cellular localization (6, 7) and oligomerization (8). How these factors relate, is unclear. We show that the established drug target, Bruton’s Tyrosine Kinase (BTK) (2, 9), integrates several levels of NLRP3 regulation: BTK phosphorylation of four conserved tyrosine residues, by neutralizing the charge of a polybasic linker region, weakens the interaction of NLRP3 with Golgi phospholipids and may thus guide NLRP3 cytosolic localization. BTK activity also promotes NLRP3 oligomerization and subsequent formation of inflammasomes. As NLRP3 tyrosine modification ultimately also impacts on IL-1β release, we propose BTK-mediated, charge-switch-based NLRP3 regulation as a novel and therapeutically tractable step in the control of inflammation.

One Sentence Summary

Multi-phosphorylation of NLRP3 by Bruton’s tyrosine kinase modulates NLRP3 cellular localization, inflammasome assembly, and IL-1β release.
Experience and relatedness influence mating interactions in a simultaneously hermaphroditic snail,Physa gyrina
Authors: McCarthy Thomas M.
Published: December 2019

The means by which animals assess potential mates is an important issue in studies of reproductive systems. I tested whether an individual’s previous experiences and the relatedness of mates affected mating behavior in a simultaneous hermaphrodite snail,Physa gyrina. Previous work with this species showed reduced reproductive success resulting from both strong outbreeding and inbreeding. Thus, I predicted that individuals should prefer partners of intermediate relatedness. During activity trials, snails moved longer distances when exposed to chemical cues from conspecifics of lesser relatedness. Furthermore, during mating interactions, behavioral responses to relatedness varied with gender-role: male-role behaviors did not vary across relatedness treatments, while snails paired with either closely related or highly dissimilar partners increased their female-role resistance behaviors as interactions escalated. Experiences with their current partner also affected behavioral dynamics. Familiar pairs had fewer matings and longer latency times until a mating occurred than unfamiliar pairs. Snails acting in the female role also exhibited higher resistance rates in familiar pairs than in unfamiliar pairs. Previous, brief exposure to chemical cues in a non-mating context also influenced behavior during a subsequent mating interaction. Snails that were previously exposed to chemical cues from unfamiliar individuals tended to be more likely to occupy the male role following an encounter, and had significantly lower copulation frequencies and higher female-role resistance rates (i.e. were choosier) than those previously exposed to cues from familiar individuals. Overall, the results show that: 1) relatedness, past exposure to conspecific chemical cues, and experience with a current partner all influence mating behaviors in these snails; and 2) in these simultaneous hermaphrodites, an individual’s responses depend on whether it is occupying the male or female role.
The trade-offs of sharing pollinators: pollination service is determined by the community context
Authors: Cagua E. Fernando , Marrero Hugo J. , Tylianakis Jason M. , Stouffer Daniel B.
Published: December 2019

A fundamental feature of pollination systems is the indirect facilitation and competition that arises when plants species share pollinators. When plants share pollinators, the pollination service can be influenced. This depends not only on how many partners plant species share, but also by multiple intertwined factors like the plant species’ abundance, visitation, or traits. These factors inherently operate at the community level. However, most of our understanding of how these factors may affect the pollination service is based on systems of up to a handful of species. By examining comprehensive empirical data in eleven natural communities, we show here that the pollination service is—surprisingly—only partially influenced by the number of shared pollinators. Instead, the factors that most influence the pollination service (abundance and visit effectiveness) also introduce a trade-off between the absolute amount of conspecific pollen received and the amount relative to heterospecific pollen. Importantly, the ways plants appear to balance these trade-offs depend strongly on the community context, as most species showed flexibility in the strategy they used to cope with competition for pollination.
The nucleus measures shape deformation for cellular proprioception and regulates adaptive morphodynamics
Authors: Venturini Valeria , Pezzano Fabio , Castro Frederic Català , Häkkinen Hanna-Maria , Jiménez-Delgado Senda , Colomer-Rosell Mariona , Sánchez Mónica Marro , Tolosa-Ramon Queralt , Paz-López Sonia , Valverde Miguel A. , Loza-Alvarez Pablo , Krieg Michael , Wieser Stefan , Ruprecht Verena
Published: December 2019

The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within their local environment remains largely unknown. Here we show that the nucleus, the biggest cellular organelle, functions as a non-dissipative cellular shape deformation gauge that enables cells to continuously measure shape variations on the time scale of seconds. Inner nuclear membrane unfolding together with the relative spatial intracellular positioning of the nucleus provides physical information on the amplitude and type of cellular shape deformation. This adaptively activates a calcium-dependent mechano-transduction pathway, controlling the level of actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behaviour to their microenvironment.

One Sentence Summary

The nucleus functions as an active deformation sensor that enables cells to adapt their behavior to the tissue microenvironment.
Hacienda Flandes: Los Altibajos De Una Finca Cafetera Colombiana
Authors: Gonzalez Ana Cristina , Ossa Vesga Henry
Published: December 2019

Supplementary materials

Las notas pedagógicas contienen materiales de lectura específicos para apoyar la discusión en clase.

Learning outcomes

Los estudiantes podrán comprender y explicar el concepto de una empresa familiar como un sistema dinámico: empresa, familia e individuos, cada uno con acciones y resultados; analizar las oportunidades y las amenazas para las empresas familiares a través de las generaciones; y formular estrategias para equilibrar las demandas de la empresa y de la familia.

Case overview/synopsis

Este caso cuenta la historia de dos generaciones de caficultores de la Hacienda Flandes, en la región cafetera de Colombia. Describe los factores externos e internos que afectaron el negocio familiar desde 1970 hasta 2013. El caso presenta los antecedentes y las consecuencias de las circunstancias medioambientales y de las decisiones de los miembros de la familia, y que llevaron el negocio desde la bonanza hasta el decaimiento y posteriormente a su posible reinvención. Se espera que los estudiantes, mediante el análisis de esta plantación de café familiar que se extiende varias generaciones, comprendan la importancia de la planeación estratégica en las empresas familiares, en el contexto de un ambiente cambiante y competitivo. Las empresas más comunes son las empresas familiares en las economías emergentes. En Latinoamérica, la mayoría de empresas familiares suelen ser más jóvenes que aquellas de Europa e incluso Norte América. Por lo tanto, las empresas familiares en estas economías pueden estar atravesando o pronto atravesarán una sucesión. La tasa de éxito de las sucesiones es baja, independientemente de la cultura o el país en el que se desarrolle la empresa. Este caso lidia con la preparación (o falta de preparación) de la siguiente generación para la administración de empresas familiares, y con las consecuencias de esto, y ayuda a los estudiantes a sugerir alternativas y mejores decisiones para dirigir empresas familiares en una economía emergente.

Complexity academic level

Cursos de MBA sobre empresas familiares y/o cursos de educación ejecutiva que se enfoquen en empresas familiares. El caso se puede usar en sesiones introductorias relacionadas con estrategia de empresas familiares.

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
Applying the Delphi method to determine best practices for outsourcing logistics in disaster relief
Authors: Gossler Timo , Falagara Sigala Ioanna , Wakolbinger Tina , Buber Renate
Published: December 2019

Purpose

The purpose of this paper is to determine best practices of aid agencies for outsourcing logistics to commercial logistics service providers (LSPs) in disaster relief. Moreover, it evaluates the application of the Delphi method for research in humanitarian logistics.

Design/methodology/approach

The paper is based on a two-round Delphi study with 31 experts from aid agencies and a complementary full-day focus group with 12 experts from aid agencies and LSPs.

Findings

The study revealed 12 best practices for outsourcing logistics in disaster relief and a compilation of more than 100 activities for putting these practices into action. Experts consider a proper balance between efficiency and compliance, a detailed contract and a detailed service request most important. Additionally, the Delphi method was found to be a promising technique for research on humanitarian logistics.

Research limitations/implications

By critically examining the Delphi method, this study establishes the basis for a wider application of the technique in the field of humanitarian logistics. Furthermore, it can help to prioritize future research as the ranking of practices reflects the priorities of practitioners.

Practical implications

The paper provides guidance to practitioners at aid agencies in charge of outsourcing logistics.

Originality/value

This research is one of the first in the field of humanitarian logistics to apply the Delphi method. Moreover, it addresses the lack of literature dealing with approaches for building successful cross-sectoral partnerships.
A comprehensive review of ultrasonic additive manufacturing
Authors: Hehr Adam , Norfolk Mark
Published: December 2019

Purpose

This paper aims to comprehensively review ultrasonic additive manufacturing (UAM) process history, technology advancements, application areas and research areas. UAM, a hybrid 3D metal printing technology, uses ultrasonic energy to produce metallurgical bonds between layers of metal foils near room temperature. No melting occurs in the process – it is a solid-state 3D metal printing technology.

Design/methodology/approach

The paper is formatted chronologically to help readers better distinguish advancements and changes in the UAM process through the years. Contributions and advancements are summarized by academic or research institution following this chronological format.

Findings

This paper summarizes key physics of the process, characterization methods, mechanical properties, past and active research areas, process limitations and application areas.

Originality/value

This paper reviews the UAM process for the first time.
Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single‐center, open‐label, prospective randomized study
Authors: Okamoto Teppei , Hatakeyama Shingo , Konishi Sakae , Okita Kazutaka , Tanaka Yoshimi , Imanishi Kengo , Takashima Tooru , Saitoh Fumitada , Suzuki Tadashi , Ohyama Chikara
Published: December 2019

The efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single‐center, open‐label, parallel‐group trial for MHD patients with serum zinc level <70 μg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6‐month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients.
“Nerve” and violent encounters: An assessment of fearlessness in the face of danger
Authors: Melde Chris , Berg Mark T. , Esbensen Finn‐Aage
Published: December 2019

The findings from a large body of research on the ecology of violence indicate that individuals demonstrate a willingness to engage in violence to reduce their risk for violent victimization. Scholars have suggested that a reputation for toughness and aggression acts as an informal signal that deters mistreatment. Anderson (1999), in his street code thesis, in particular, argued that adherence to the street code functions as a signal that reduces violent victimization risk. Other research findings, however, reveal that the street code leads to an increase in victimization risk; moreover, violent offenders are routinely victimized at high rates given their lifestyle and routine activities. The evidence, therefore, does not show support for the position that a reputation for toughness or aggression effectively reduces violent victimization. In the current study, we operationalize the concept of nerve, which findings from criminological studies indicate is an important mechanism for protecting adolescents from victimization. Using data from the second national evaluation of the Gang Resistance Education and Training Program, we test this operationalization of nerve to determine whether the concept is associated with later violent offending and violent victimization in ways consistent with theory and research on the ecology of youth violence. Our results demonstrate support for the notion that nerve is positively associated with violent offending, whereas those at the highest levels of this construct experience fewer violent victimizations.
The cost to perform uterine fibroid embolisation in the Australian public hospital system
Authors: Clements Warren , Moriarty Heather K , Koukounaras Jim , Joseph Tim , Phan Tuan , Goh Gerard S
Published: December 2019

Introduction

Uterine fibroids have the potential to cause morbidity, and there is a substantial cost to both the healthcare system and society. There is support for minimally invasive intervention, and uterine fibroid embolisation (UFE) is an established cost‐effective option for women wishing for an alternative to surgery. There is a lack of local Australian costing data to compliment use in the public hospital system, and we offer a costing analysis of running a public hospital service.

Methods

We reviewed the costs for 10 sequential uterine fibroid embolisation cases, by assessing the direct and indirect hospital costs.

Results

The total cost of providing a uterine fibroid embolisation service using our model in a public hospital including initial outpatient assessment, procedure costs, overnight hospital ward stay and outpatient follow‐up is $3995 per admission.

Conclusion

Using our model, the overall cost to perform this procedure is low, and lower than prior estimates for surgical alternatives. We encourage government and regulatory bodies to support UFE through guidelines and remuneration models, and encourage more public Australian interventional radiology departments to offer this service.
Genetic liability to ADHD and substance use disorders in individuals with ADHD
Authors: Wimberley Theresa , Agerbo Esben , Horsdal Henriette Thisted , Ottosen Cæcilie , Brikell Isabell , Als Thomas Damm , Demontis Ditte , Børglum Anders D. , Nordentoft Merete , Mors Ole , Werge Thomas , Hougaard David , Bybjerg‐Grauholm Jonas , Hansen Marie Bækvad , Mortensen Preben Bo , Thapar Anita , Riglin Lucy , Langley Kate , Dalsgaard Søren
Published: December 2019

Aims

1) To investigate whether genetic liability to attention‐deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS‐ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual‐ or family‐related risk factors for SUD could mediate or confound this association.

Design

Population‐based cohort study

Setting and participants

ADHD cases in the iPSYCH sample (a Danish case‐cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register‐based information on hospital diagnoses of SUD was available until December 31, 2016.

Measurements

We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS‐ADHD decile to the lowest.

Findings

PRS‐ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11–1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio‐economic status) were independently associated with increased risk of SUD. PRS‐ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS‐ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03–1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales = 1.59, 95% CI: 1.19–2.12, ORmales = 1.18, 95% CI: 0.98–1.42).

Conclusions

A higher genetic liability to attention‐deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention‐deficit/hyperactivity disorder.
Efficacy of mifepristone and misoprostol for medical treatment of missed miscarriage in clinical practice—A cohort study
Authors: Ehrnstén Lisa , Altman Daniel , Ljungblad Anton , Kopp Kallner Helena
Published: November 2019

Introduction

It has been estimated that one out of every four women experience first‐trimester miscarriage. Missed miscarriage is a common form of early miscarriage where the products of conception are not expelled from the uterus. It is diagnosed by ultrasound. The primary objective of this study was to evaluate the success rate of a combination treatment with mifepristone and misoprostol for missed miscarriage in clinical practice. The secondary objective was to identify significant factors influencing the rate of success.

Material and methods

A cohort of 941 consecutive women with an ICD‐10 diagnosis of missed miscarriage who received treatment with 800 µg vaginal misoprostol and 2 repeat doses of 400 µg oral misoprostol after mifepristone pretreatment between 1 January 2012 and 31 December 2014 was analyzed. Women with a uterine size smaller than 12 weeks who were planned for medical treatment were included in the study. The exclusion criteria were primary surgical management or planned follow up outside the Stockholm County Council area.

Results

The success rate of medical treatment, defined as no need for surgical treatment, was 85.5% (805/941) in women with a uterine size of less than 12 weeks. However, for women with uterine size below 9 weeks the success rate was 88.9% (586/659). Indeed, uterine size of 9 gestational weeks or larger at time of treatment was identified as the only significant risk factor for surgical intervention.

Conclusions

The medical regimen for missed miscarriage offered in this study appears to be safe and with high rates of success. Conclusions about which women to exclude from medical treatment could not be made. Medical treatment may therefore benefit all women with missed miscarriage who wish to avoid primary surgery.
An analytical relation between the Weibull and Basquin laws for smooth and notched specimens and application to constant amplitude fatigue
Authors: D'Antuono Pietro
Published: December 2019

Starting from the classical definition of stress‐life Wöhler curve in the form of the Basquin law, an analytical procedure for the calibration of the four parameters' Wöhler curve (the Weibull law) for a plain specimen is proposed. The obtained parameters are then adjusted by means of an additional slope factor preserving the inflection point of the curve while changing its slope in order to model the experimental observations in which an increase of the scatter in life prediction is observed when reducing the stress amplitude. The same approach has then been adopted to calibrate the Weibull law parameters for a notched specimen, and the fitting slope factor has been found to be a value that changes with the material but remains constant with the stress concentration factor. The findings have been validated with existing experimental data on 2024‐T3 aluminum alloy and normalized SAE 4130 steel.
Spinal muscular atrophy with respiratory distress type 1: Clinical phenotypes, molecular pathogenesis and therapeutic insights
Authors: Saladini Matteo , Nizzardo Monica , Govoni Alessandra , Taiana Michela , Bresolin Nereo , Comi Giacomo P. , Corti Stefania
Published: December 2019

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder caused by mutations in the IGHMBP2 gene, which encodes immunoglobulin μ‐binding protein 2, leading to progressive spinal motor neuron degeneration. We review the data available in the literature about SMARD1. The vast majority of patients show an onset of typical symptoms in the first year of life. The main clinical features are distal muscular atrophy and diaphragmatic palsy, for which permanent supportive ventilation is required. No effective treatment is available yet, but novel therapeutic approaches, such as gene therapy, have shown encouraging results in preclinical settings and thus represent possible methods for treating SMARD1. Significant advancements in the understanding of both the SMARD1 clinical spectrum and its molecular mechanisms have allowed the rapid translation of preclinical therapeutic strategies to human patients to improve the poor prognosis of this devastating disease.