bluuebunny/crossref_metadata_2025 huggingface dataset:
Adulticidal Activity of Metarhizium anisopliae s.l. (Hypocreales: Clavicipitaceae) Native Strains From Argentina Against Aedes aegypti (Diptera: Culicidae)
Authors: Falvo Marianel L , Musso Anahi , Ordoqui Eliana , López Lastra Claudia C , Luz Christian , García Juan J
Published: November 2019

The adulticidal activity of six fungal strains of Metarhizium anisopliae (Metschn.) Sorokin s.l. (Hypocreales: Clavicipitaceae) against Aedes aegypti (L.) (Diptera: Culicidae) was assessed. These strains (CEP 085, CEP 087, CEP 120, CEP 350, CEP 404, and CEP 423) were isolated from soil samples or nondipteran hosts collected from areas in Argentina where Ae. aegypti is distributed. Bioassays were performed with four conidial concentrations plus a control of each fungal strain to determine the lethal concentrations (LC50/LC90), the median survival times (ST50), the mean percentage of the surviving individuals, and the mean percentage of mycotized cadavers. The strains were able to infect and kill adult Ae. aegypti. Significant differences were found among the LC50 values, with CEP 423 as the most virulent strain with the lowest LC50 (2.4 × 106 conidia/ml). At 1 × 107 conidia/ml: no significant differences were found in the Kaplan–Meier survival functions among the strains; the ST50 ranged from 5 (CEP 085) to 8 d (CEP 350); and the mean percentage of the surviving adults was between 13.3 (CEP 085, CEP 350 and CEP 423) and 46.7% (CEP 087). Significant differences were also found among strains in the mean percentage of cadavers with fungal sporulation. Strain CEP 423 produced the highest percentage of mycotized adults (70%). The concentration of the inoculum significantly affected the survival of individuals and the percentage of mycotized cadavers within each strain. Metarhizium anisopliae s.l. CEP 423 was selected as the most promising candidate for further research aiming to develop a mycoinsecticide against Ae. aegypti.
First Use of an Entire Age Cohort to Evaluate the Role of Sex in the Development of the Forensically Important Chrysomya megacephala (Diptera: Calliphoridae)
Authors: Smith Joshua L , Cook Ashley K
Published: November 2019

The age of a blow fly larval specimen found on a body can be used to estimate a minimum postmortem interval by comparing a physical feature of a larva (e.g., length) to a reference growth curve created under similar conditions. A better understanding of factors known to influence growth rates would lead to more precise estimates of larval age. A factor known to influence insect development, but almost always lacking in blow fly larval growth curves, is sex. We wanted to understand how sex might affect larval growth rates and therefore lead to more precise age estimates, in the forensically important blow fly Chrysomya megacephala (F.). We examined sex for an entire age cohort at 70 h and found on average, males were longer than females. To assess whether this difference would cause an investigator to interpret the results differently if comparing a larval specimen of one sex based on reference data from the other sex, we made sex-specific 95% prediction intervals. We did not find a difference when comparing a male specimen with the female prediction interval, but did find more females outside the interval than expected using the male interval. All females outside the male interval were shorter. Investigators commonly remove the largest individuals from a body to estimate age, so these females are less likely to be chosen. These results do not support the generation of sex-specific growth curves for this species, though this study’s narrow scope means more information is required before making a final conclusion.
Surveillance of a kdr Resistance Mutation in Culex pipiens (Diptera: Culicidae) and Culex quinquefasciatus in California
Authors: Yoshimizu Melissa Hardstone , Padgett Kerry , Kramer Vicki
Published: November 2019

Culex pipiens Linnaeus and Culex quinquefasciatus Say are the primary vectors of West Nile and St. Louis encephalitis viruses in California. Pyrethrins and pyrethroids (synthetic pyrethrins) are the most widely used insecticides to control adult stage mosquitoes to prevent disease transmission. The most abundant and widespread mutation associated with pyrethroid resistance is the L1014F mutation of the voltage-sensitive sodium channel gene. Statewide, based on the testing of almost 2,000 mosquitoes from 14 counties, the resistant allele frequency was 71%. Although the L1014F mutation was found in all counties assessed, the resistance allele profiles differed between regions of California. The highest resistant allele frequency occurred in the Central region and lowest frequencies were from the Northern and Southern regions. Resistance allele frequencies observed in 2014–2016 are nearly 1.5 times higher than those from pre-2012, indicating that resistance profiles can change over time. Regular monitoring of the L1014F kdr mutation will help aid in operational decisions.
Comparison of Physician Data in Two Data Files Available for Cancer Health Services Research
Authors: White Dolly P , Enewold Lindsey , Geiger Ann M , Banks Robert , Warren Joan L
Published: November 2019

Introduction

Physicians are vital to health-care delivery, but assessing their impact on care can be challenging given limited data. Historically, health services researchers have obtained physician characteristics data from the American Medical Association (AMA) Physician Masterfile. The Center for Medicare and Medicaid Services’ Medicare Data on Provider Practice and Specialty (MD-PPAS) file was assessed, as an alternative source of physician data, particularly in the context of cancer health services research.

Methods

We used physician National Provider Identifiers in the MD-PPAS data (2008–2014) to identify physicians in the AMA data current as of July 18, 2016. Within each source, we grouped physicians into six broad specialty groups. Percent agreement and Cohen’s kappa coefficient (k) were calculated for age, sex, specialty, and practice state.

Results

Among the 698 202 included physicians, there was excellent agreement for age (percent agreement = 97.7%, k = 0.97) and sex (99.4%, k = 0.99) and good agreement for specialty (86.1%, k = 0.80). Within specialty, using AMA as the reference, agreement was lowest for oncologists (77%). Approximately 85.9% of physicians reported the same practice state in both data sets.

Conclusion

Although AMA data have been commonly used to account for physician-level factors in health services research, MD-PPAS data provide researchers with an alternative option depending on study needs. MD-PPAS data may be optimal if nonphysicians, provider utilization, practice characteristics, and/or temporal changes are of interest. In contrast, the AMA data may be optimal if more granular specialty, physician training, and/or a broader inclusion of physicians is of interest.
The ‘Host’ Label: Forming and Transforming a Community Identity at the Kakuma Refugee Camp
Authors: Rodgers Cory
Published: November 2019

In 1986, Robert Chambers argued that refugee-centric responses to displacement tend to neglect the populations that host them. Three decades later, the Comprehensive Refugee Response Framework (CRRF) has made assistance to host communities a matter of high priority for agencies, policymakers and other stakeholders involved in refugee protection. While recognizing the progressive principles of responsibility sharing and inclusivity that underlie this shift, this article calls for greater critical attention to the meaning of the term ‘host community’ and the ways in which it is applied. Taking the Kakuma refugee camps in north-western Kenya as a case study, I describe the rise of a ‘host community’ identity in the context of humanitarian programming, contested attempts to define it as a bureaucratic label and its transformations under a socio-economic-integration agenda. While the case presented here is specific to Kenya, the argument is relevant more broadly as hosts are brought under the purview of refugee-protection policies, especially in countries implementing the CRRF.
Public Speaking
Authors: Hope Debra A. , Heimberg Richard G. , Turk Cynthia L.
Published: November 2019

Fear of public speaking is nearly always listed as the number 1 fear experienced by the general public in national surveys in the United States. It has been found that fear of public speaking is extremely common among individuals with social anxiety disorder. Over 90% reported at least some fear about speaking in front of a group, and for most of those individuals, the fear is moderate or severe. There are many forms of public speaking that most people confront much more frequently. Common automatic thoughts reported by individuals with public speaking fears usually center on the visibility of anxiety symptoms or concerns about the quality of one’s performance.
Working Alliance Skills for Healthcare Professionals
Authors: Fuertes Jairo N. , Mele Patrick , Rapaport Julian
Published: November 2019

In this chapter, the authors provide a brief overview of the history of the working alliance and a brief summary of the primary empirical findings on the topic to date. They also provide a rationale for the current book, including the need to better advance training in working alliance skills in graduate programs and, relatedly, the need for examples of in-session interventions that can help beginning as well as advanced clinicians establish stronger working alliances with their clients. A brief description is given of the chapters making up the book, along with an overall summary of the importance of educating students in the skills needed to form and maintain the working alliance with clients.
Therapeutic Interpersonal Skills for Facilitating the Working Alliance
Authors: Anderson Timothy , Perlman Matthew R.
Published: November 2019

The authors focus on the interpersonal skills that can be cultivated to promote a productive working alliance between therapist and client/patient. Specifically, they identify pan-theoretical, pragmatic methods of improving therapist interpersonal skills with the goal of establishing and maintaining working alliances. The authors review the eight facilitative interpersonal skills (FIS) and discuss the role of therapist responsiveness—the ability to detect and modify in-session processes based on subtle, interpersonal shifts in the client’s expression and communication. Therapist responsiveness and the use of FIS is of particular importance during challenging, emotionally charged incidents during therapy, known as “critical relational markers.” Finally, they discuss how therapists can foster these relational capacities through deliberate practice. Clinical examples are utilized to facilitate understanding of the application of these skills.
Multicultural Considerations in the Working Alliance
Authors: Duan Changming
Published: November 2019

The author addresses the importance of the working alliance from a multicultural perspective. In order to best serve the needs of racial/ethnic minority clients, it is critical to acknowledge and consider their differential social and cultural realities, as well as the therapists’ own sociocultural contexts. Therapists may need to be intentional in their attempt to connect with racial/ethnic minority clients by developing appreciation and respect for cultural diversity. The appreciation and respect for cultural diversity that is developed from therapist’s self-work can then facilitate an open, accepting, honest, and empathic working relationship with racial/ethnic minority clients. The author of this chapter provides clinical examples and specific therapeutic skills that can foster the working alliance with racial/ethnic minority clients.
Artificial Womb Technology and the Choice to Gestate Ex Utero: Is Partial Ectogenesis the Business of the Criminal Law?
Authors: Romanis Elizabeth Chloe
Published: November 2019

It is frequently claimed that artificial wombs (AWs) could alleviate the burdens placed exclusively on women in reproduction. In this article, I demonstrate how AWs used for the partial gestation of preterm neonates could introduce new choices for women by changing perceptions of tolerable risks in gestation. In light of advancing medical technology, it is necessary to consider whether the current legal framework in England and Wales would support increased choice for women about alternative forms of gestation. I examine the ill-defined offence of ‘unlawfully procuring miscarriage’ in the Offences Against the Person Act 1861 and demonstrate that different conclusions about the legal significance of ending a pregnancy are evident, depending on the analytical lens adopted in interpreting ambiguities. Furthermore, I demonstrate that the defences available to pregnancy termination under the Abortion Act 1967 are too narrow to support choices about alternative forms of gestation, even if they become physically and medically possible. Therefore, we should decriminalise termination of pregnancy, or, if it is assumed that gestation is the business of the criminal law, specific reforms to the legal framework are necessary. The offence of unlawfully procuring miscarriage is too uncertain and broad, and the defences available are too restrictive.
An optical search for transients lasting a few seconds
Authors: Richmond Michael W , Tanaka Masaomi , Morokuma Tomoki , Sako Shigeyuki , Ohsawa Ryou , Arima Noriaki , Tominaga Nozomu , Doi Mamoru , Aoki Tsutomu , Arimatsu Ko , Ichiki Makoto , Ikeda Shiro , Ita Yoshifusa , Kasuga Toshihiro , Kawabata Koji S , Kawakita Hideyo , Kobayashi Naoto , Kokubo Mitsuru , Konishi Masahiro , Maehara Hiroyuki , Mito Hiroyuki , Miyata Takashi , Mori Yuki , Morii Mikio , Motohara Kentaro , Nakada Yoshikazu , Okumura Shin-Ichiro , Onozato Hiroki , Sarugaku Yuki , Sato Mikiya , Shigeyama Toshikazu , Soyano Takao , Takahashi Hidenori , Tanikawa Ataru , Tarusawa Ken’ichi , Urakawa Seitaro , Usui Fumihiko , Watanabe Junichi , Yamashita Takuya , Yoshikawa Makoto
Published: November 2019

Using a prototype of the Tomo-e Gozen wide-field CMOS mosaic camera, we acquire wide-field optical images at a cadence of $2\:$Hz and search them for transient sources of duration 1.5 to $11.5\:$s. Over the course of eight nights, our survey encompasses the equivalent of roughly two days on one square degree, to a fluence equivalent to a limiting magnitude of about $V = 15.6$ in a 1-s exposure. After examining by-eye the candidates identified by a software pipeline, we find no sources which meet all our criteria. We compute upper limits to the rate of optical transients consistent with our survey, and compare those to the rates expected and observed for representative sources of ephemeral optical light.
Electrostatic interactions modulate the differential aggregation propensities of IgG1 and IgG4P antibodies and inform charged residue substitutions for improved developability
Authors: Heads James T , Lamb Richard , Kelm Sebastian , Adams Ralph , Elliott Peter , Tyson Kerry , Topia Sarfaraj , West Shauna , Nan Ruodan , Turner Alison , Lawson Alastair D G
Published: November 2019

Native state aggregation is an important concern in the development of therapeutic antibodies. Enhanced knowledge of mAb native state aggregation mechanisms would permit sequence-based selection and design of therapeutic mAbs with improved developability. We investigated how electrostatic interactions affect the native state aggregation of seven human IgG1 and IgG4P mAb isotype pairs, each pair having identical variable domains that are different for each set of IgG1 and IgG4P constructs. Relative aggregation propensities were determined at pH 7.4, representing physiological conditions, and pH 5.0, representing commonly used storage conditions. Our work indicates that the net charge state of variable domains relative to the net charge state of the constant domains is predominantly responsible for the different native state aggregation behavior of IgG1 and IgG4P mAbs. This observation suggests that the global net charge of a multi domain protein is not a reliable predictor of aggregation propensity. Furthermore, we demonstrate a design strategy in the frameworks of variable domains to reduce the native state aggregation propensity of mAbs identified as being aggregation-prone. Importantly, substitution of specifically identified residues with alternative, human germline residues, to optimize Fv charge, resulted in decreased aggregation potential at pH 5.0 and 7.4, thus increasing developability.
G-Graph: An interactive genomic graph viewer
Authors: Andrews Peter A. , Alexander Joan , Kendall Jude , Wigler Michael
Published: November 2019

Motivation

Effective and efficient exploration of numeric data and annotations as a function of genomic position requires specialized software.

Results

We present G-Graph, an interactive genomic scatter plot viewer. G-Graph stacks or tiles multiple data series in one graph using different colors and markers. It displays gene annotation and other metadata, allows easy changes to the appearance of data series, implements stack-based undo functionality, and saves user-selected application views as image and pdf files. G-Graph delivers smooth and rapid scrolling and zooming even for datasets with millions of points and line segments. The primary target user is a researcher examining many copy number profiles to identify potentially deleterious variants. G-Graph runs under Linux, Mac OSX and Windows.

Availability

https://github.com/docpaa/mumdex/ or https://mumdex.com/ggraph/

Contact

andrewsp@cshl.edu (or paa@drpa.us)
Predictive coding models for pain perception
Authors: Song Yuru , Yao Mingchen , Kemprecos Helen , Byrne Áine , Xiao Zhengdong , Zhang Qiaosheng , Singh Amrita , Wang Jing , Chen Zhe S.
Published: November 2019

Pain is a complex, multidimensional experience that involves dynamic interactions between sensory-discriminative and affective-emotional processes. Pain experiences have a high degree of variability depending on their context and prior anticipation. Viewing pain perception as a perceptual inference problem, we propose a predictive coding paradigm to characterize evoked and non-evoked pain. We record the local field potentials (LFPs) from the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC) of freely behaving rats—two regions known to encode the sensory-discriminative and affective-emotional aspects of pain, respectively. We further use predictive coding to investigate the temporal coordination of oscillatory activity between the S1 and ACC. Specifically, we develop a phenomenological predictive coding model to describe the macroscopic dynamics of bottom-up and top-down activity. Supported by recent experimental data, we also develop a biophysical neural mass model to describe the mesoscopic neural dynamics in the S1 and ACC populations, in both naive and chronic pain-treated animals. Our proposed predictive coding models not only replicate important experimental findings, but also provide new prediction about the impact of the model parameters on the physiological or behavioral read-out—thereby yielding mechanistic insight into the uncertainty of expectation, placebo or nocebo effect, and chronic pain.
Geometric principles underlying the proliferation of a model cell system
Authors: Wu Ling Juan , Lee Seoungjun , Park Sungshic , Eland Lucy E. , Wipat Anil , Holden Seamus , Errington Jeff
Published: November 2019

Wall deficient variants of many bacteria, called L-forms, divide by a simple mechanism that does not depend on the complex FtsZ-based cell division machine. We have used microfluidic systems to probe the growth, chromosome cycle and division mechanism ofBacillus subtilisL-forms. The results show that forcing cells into a narrow linear configuration greatly improves the efficiency of cell growth and chromosome segregation. This reinforces the view that L-form division is driven by an excess accumulation of surface area over volume. Cell geometry was also found to play a dominant role in controlling the relative positions and movement of segregating chromosomes. The presence of the nucleoid appears to influence division both via a cell volume effect and by nucleoid occlusion, even in the absence of the FtsZ machine. Overall, our results emphasise the importance of geometric effects for a range of critical cell functions and are of relevance for efforts to develop artificial or minimal cell systems.
The kinesin-8 Kip3 depolymerizes microtubules with a collective force-dependent mechanism
Authors: Bugiel Michael , Chugh Mayank , Jörg Jachowski Tobias , Schäffer Erik , Jannasch Anita
Published: November 2019

Microtubules are highly dynamic filaments with dramatic structural rearrangements and length changes during the cell cycle. An accurate control of the microtubule length is essential for many cellular processes in particular, during cell division. Motor proteins from the kinesin-8 family depolymerize microtubules by interacting with their ends in a collective and length-dependent manner. However, it is still unclear how kinesin-8 depolymerizes microtubules. Here, we tracked the microtubule end-binding activity of yeast kinesin-8, Kip3, under varying loads and nucleotide conditions using high-precision optical tweezers. We found that single Kip3 motors spent up to 200 s at the microtubule end and were not stationary there but took several 8-nm forward and backward steps that were suppressed by loads. Interestingly, increased loads, similar to increased motor concentrations, also exponentially decreased the motors’ residence time at the microtubule end. On the microtubule lattice, loads also exponentially decreased the run length and time. However, for the same load, lattice run times were significantly longer compared to end residence times suggesting the presence of a distinct force-dependent detachment mechanism at the microtubule end. The force dependence of the end residence time enabled us to estimate what force must act on a single motor to achieve the microtubule depolymerization speed of a motor ensemble. This force is higher than the stall force of a single Kip3 motor, supporting a collective force-dependent depolymerization mechanism that unifies the so-called “bump-off” and “switching” models. Understanding the mechanics of kinesin-8’s microtubule end activity will provide important insights into cell division with implications for cancer research.

STATEMENT OF SIGNIFICANCE

Kinesin-8 motors are important for microtubule length regulation and are over-expressed in different types of cancer. Yet, on the molecular level, it is unclear how these motors depolymerize microtubules. Using high-precision optical tweezers, we measured how single yeast kinesin-8 motors, Kip3, interacted with the microtubule end. Interestingly, we found that single Kip3 motors were still motile at the microtubule end. The force dependence of how long single motors were associated with the microtubule end enabled us to estimate what force motors must exert onto each other to achieve the collective microtubule depolymerization speed of many motors. Our data support a collective force-dependent depolymerization mechanism. A better understanding of Kip3’s microtubule end activity has implications for cell division and associated diseases.
Differential robustness to specific potassium channel deletions in midbrain dopaminergic neurons
Authors: Haddjeri-Hopkins Alexis , Marqueze-Pouey Béatrice , Tapia Monica , Tell Fabien , Amalric Marianne , Goaillard Jean-Marc
Published: November 2019

The authors have withdrawn this preprint titled “Differential robustness to specific potassium channel deletions in midbrain dopaminergic neurons”. Upon review of breeding and genotyping data, Kcnn3-/- mice could not be trusted as representative of the expected genetic deletion. As a consequence data generated from these animals do not constitute a valid description of the Kcnn3-/- genotype in dopaminergic neurons. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Isogenic sets of hiPSC-CMs harboringKCNH2mutations capture location-related phenotypic differences
Authors: Brandão Karina O. , van den Brink Lettine , Miller Duncan C. , Grandela Catarina , van Meer Berend J. , Mol Mervyn P.H. , Tertoolen Leon G.J. , Mummery Christine L. , Sala Luca , Verkerk Arie O. , Davis Richard P.
Published: November 2019

Aims

Long QT syndrome type 2 (LQT2) is caused by mutations in the geneKCNH2, encoding the hERG ion channel. Clinically, mild and severe phenotypes are associated with this cardiac channelopathy, complicating efforts to predict patient risk. The location of the mutation withinKCNH2contributes to this variable disease manifestation. Here we determined whether such phenotypic differences could be detected in cardiomyocytes derived from isogenic human induced pluripotent stem cells (hiPSCs) genetically edited to harbour a range ofKCNH2mutations.

Methods and Results

The hiPSC lines heterozygous for missense mutations either within the pore or tail region of the ion channel were generated using CRISPR-Cas9 editing and subsequently differentiated to cardiomyocytes (hiPSC-CMs) for functional assessment. Electrophysiological analysis confirmed the mutations prolonged the action potentials and field potentials of the hiPSC-CMs, with differences detected between the pore and tail region mutations when measured as paced 2D monolayers. This was also reflected in the cytosolic Ca2+transients and contraction kinetics of the different lines. Pharmacological blocking of the hERG channel in the hiPSC-CMs also revealed that mutations in the pore-loop region conferred a greater susceptibility to arrhythmic events.

Conclusion

These findings establish that subtle phenotypic differences related to the location of theKCNH2mutation in LQT2 patients are reflected in hiPSC-CMs under genetically controlled conditions. Moreover, the results validate hiPSC-CMs as a strong candidate for evaluating the underlying severity of individualKCNH2mutations in humans which could ultimately facilitate patient risk stratification.

Translational perspective

Clinical management of patients diagnosed with cardiac channelopathy diseases such as LQT2 is complicated by the variable disease phenotypes observed among mutation carriers, creating challenges for diagnosis, risk stratification and treatment. The genotype of the patient contributes to this clinical heterogeneity, with the influence of the mutation’s location withinKCNH2on a patient’s risk of a cardiac event being an example. Here we demonstrate that under stringently controlled genetic and experimental conditions, hiPSC-CMs are able to reflect these subtle genotype-phenotype differences, thereby providing new opportunities to stratify and potentially lessen sudden cardiac death risk amongstKCNH2mutation carriers.
Long-term molecular evolutionary rate determines intraspecific genetic diversity
Authors: Wu Jiaqi , Yonezawa Takahiro , Kishino Hirohisa
Published: November 2019

What determines genetic diversity and how it connects to the various biological traits is unknown. In this work, we offer answers to these questions. By comparing genetic variation of 14,671 mammalian gene trees with thousands of individual genomes of human, chimpanzee, gorilla, mouse and dog/wolf, we found that intraspecific genetic diversity is determined by long-term molecular evolutionary rates, rather thande novomutation rates. This relationship was established during the early stage of mammalian evolution. Expanding this new finding, we developed a method to detect fluctuations of species-specific selection on genes as the deviations of intra-species genetic diversity predicted from long-term rates. We show that the evolution of epithelial cells, rather than of connective tissue, mainly contributes to morphological evolution of different species. For humans, evolution of the immune system and selective sweeps subjected by infectious diseases are most representative of adaptive evolution.
Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation
Authors: Marchingo Julia M. , Sinclair Linda V. , Howden Andrew J. M. , Cantrell Doreen A.
Published: November 2019

T cell expansion and differentiation are critically dependent on the transcription factor c-Myc (Myc). Herein we use quantitative mass-spectrometry to reveal how Myc controls antigen receptor driven cell growth and proteome restructuring in T cells. Analysis of copy numbers per cell of >7000 proteins provides new understanding of the selective role of Myc in controlling the protein machinery that govern T cell fate. The data identify both Myc dependent and independent metabolic processes in immune activated T cells. We uncover that a primary function of Myc is to control expression of multiple amino acid transporters and that loss of a single Myc-controlled amino acid transporter effectively phenocopies the impact of Myc deletion. This study provides a comprehensive map of how Myc selectively shapes T cell phenotypes, revealing that Myc induction of amino acid transport is pivotal for subsequent bioenergetic and biosynthetic programs and licences T cell receptor driven proteome reprogramming.
SNP-CRISPR: a web tool for SNP-specific genome editing
Authors: Chen Chiao-Lin , Rodiger Jonathan , Chung Verena , Viswanatha Raghuvir , Mohr Stephanie E. , Hu Yanhui , Perrimon Norbert
Published: November 2019

CRISPR-Cas9 is a powerful genome editing technology in which a single guide RNA (sgRNA) confers target site specificity to achieve Cas9-mediated genome editing. Numerous sgRNA design tools have been developed based on reference genomes for humans and model organisms. However, existing resources are not optimal as genetic mutations or single nucleotide polymorphisms (SNPs) within the targeting region affect the efficiency of CRISPR-based approaches by interfering with guide-target complementarity. To facilitate identification of sgRNAs (1) in non-reference genomes, (2) across varying genetic backgrounds, or (3) for specific targeting of SNP-containing alleles, for example, disease relevant mutations, we developed a web tool, SNP-CRISPR (https://www.flyrnai.org/tools/snp_crispr/). SNP-CRISPR can be used to design sgRNAs based on public variant data sets or user-identified variants. In addition, the tool computes efficiency and specificity scores for sgRNA designs targeting both the variant and the reference. Moreover, SNP-CRISPR provides the option to upload multiple SNPs and target single or multiple nearby base changes simultaneously with a single sgRNA design. Given these capabilities, SNP-CRISPR has a wide range of potential research applications in model systems and for design of sgRNAs for disease-associated variant correction.
Non-merohedral twinning: from minerals to proteins
Authors: Sevvana Madhumati , Ruf Michael , Usón Isabel , Sheldrick George M. , Herbst-Irmer Regine
Published: November 2019

In contrast to twinning by merohedry, the reciprocal lattices of the different domains of non-merohedral twins do not overlap exactly. This leads to three kinds of reflections: reflections with no overlap, reflections with an exact overlap and reflections with a partial overlap of a reflection from a second domain. This complicates the unit-cell determination, indexing, data integration and scaling of X-ray diffraction data. However, with hindsight it is possible to detwin the data because there are reflections that are not affected by the twinning. In this article, the successful solution and refinement of one mineral, one organometallic and two protein non-merohedral twins using a common strategy are described. The unit-cell constants and the orientation matrices were determined by the programCELL_NOW. The data were then integrated withSAINT.TWINABSwas used for scaling, empirical absorption corrections and the generation of two different data files, one with detwinned data for structure solution and refinement and a second one for (usually more accurate) structure refinement against total integrated intensities. The structures were solved by experimental phasing usingSHELXTfor the first two structures andSHELXC/D/Efor the two protein structures; all models were refined withSHELXL.
The use of statistics in social sciences
Authors: Maravelakis Petros
Published: November 2019

Purpose

The purpose this paper is to review some of the statistical methods used in the field of social sciences.

Design/methodology/approach

A review of some of the statistical methodologies used in areas like survey methodology, official statistics, sociology, psychology, political science, criminology, public policy, marketing research, demography, education and economics.

Findings

Several areas are presented such as parametric modeling, nonparametric modeling and multivariate methods. Focus is also given to time series modeling, analysis of categorical data and sampling issues and other useful techniques for the analysis of data in the social sciences. Indicative references are given for all the above methods along with some insights for the application of these techniques.

Originality/value

This paper reviews some statistical methods that are used in social sciences and the authors draw the attention of researchers on less popular methods. The purpose is not to give technical details and also not to refer to all the existing techniques or to all the possible areas of statistics. The focus is mainly on the applied aspect of the techniques and the authors give insights about techniques that can be used to answer problems in the abovementioned areas of research.
Measuring the use of knowledge management systems in supply firms
Authors: Centobelli Piera , Cerchione Roberto , Esposito Emilio
Published: November 2019

Purpose

This paper aims to propose a taxonomic scheme of knowledge management systems (KMSs) and a set of technologies and managerial practices supporting supply firms in knowledge management processes.

Design/methodology/approach

Based on a field analysis involving a sample of suppliers operating in high-tech manufacturing and service industries, this paper investigates the use of KMSs in the sample investigated.

Findings

The paper shows that suppliers are generally reluctant to use updated and innovative KMSs replacing traditional ones. This gap confirms that suppliers have difficulties in facing rapid technological changes. The field analysis also points out that suppliers investigated perceive knowledge management mainly as an issue of knowledge transfer and knowledge storage while appear to be neglected the phase of knowledge creation.

Originality/value

Moreover, the paper highlights a misalignment between the intensity of use of knowledge management practices that support the phase of knowledge creation and knowledge management tools that should support such practices.
Five‐year results of a modified left atrial maze IV procedure in the treatment of atrial fibrillation: a randomized study
Authors: Zhang Dengshen , Shi Jun , Quan Huayan , Liu Lu , Zhang Jian , Guo Yingqiang
Published: November 2019

Background

The left atrial maze IV (LAM‐IV) alone has been used to eliminate atrial fibrillation (AF) without severe right heart diseases. However, we felt that it could be improved and developed a modified LAM‐IV (MLAM‐IV). In this prospective trial, we aimed to investigate 5‐year clinical outcomes of AF in patients treated by the novel MLAM‐IV technique.

Methods

Between September 2012 and October 2013, 120 patients who underwent valve surgery and bipolar radiofrequency ablation for AF were randomized into the LAM‐IV group (n = 60) or MLAM‐IV group (n = 60). At postoperative follow‐up examinations, data were recorded at 1, 3 and 6 months, and annually thereafter.

Results

The mean ablation time and postoperative ventilation time were shorter in the MLAM‐IV group than in the LAM‐IV group (P < 0.001 and P = 0.03, respectively). At 5 years, the rate of freedom from AF was 69.0% in the MLAM‐IV group and 60.0% in the LAM‐IV group (hazard ratio 0.71, 95% confidence interval 0.39 to 1.32, P = 0.42). There were no differences with respect to the early operative mortality and major complications, late mortality, and major adverse events.

Conclusions

The MLAM‐IV provides a technically simpler ablation process. The MLAM‐IV was associated with less ventilation support in the early postoperative period. The long‐term efficacy of the MLAM‐IV in the treatment of AF is comparable to that of the LAM‐IV.
Front Cover
Authors: Rao Man , Guo Guangran , Li Mengmeng , Chen Shi , Chen Kai , Chen Xiao , Song Jiangping , Hu Shengshou
Published: November 2019

The cover image is based on the Original Article The homozygous variant c.245G > A/p.G82D in PNPLA2 is associated with arrhythmogenic cardiomyopathy phenotypic manifestations by Man Rao et al., https://doi.org/10.1111/cge.13642.

image
Early ischemia identification employing 2D speckle tracking selective layers analysis during dobutamine stress echocardiography
Authors: Cadeddu Dessalvi Christian , Deidda Martino , Farci Salvatore , Longu Giorgio , Mercuro Giuseppe
Published: November 2019

Purpose

Two‐dimensional (2D) strain derived from speckle tracking proved to be feasible and accurate in the quantitative evaluation of myocardial ischemia during stress echocardiography. We compared the accuracy in detecting myocardial ischemia of the transmural segmental analysis with an endocardial specific evaluation in 20 patients undergoing dobutamine stress echocardiography (DSE) and coronary angiography.

Methods

Peak systolic global strain (G‐ε) and at the subendocardial level (Endo‐ε) were measured off‐line at rest, a low dose, and peak stress; then, we compared the results with wall‐motion analysis and significant coronary artery disease (CAD > 70% diameter stenosis). Endocardial strain variation from basal to low and peak dose was computed both for global or subendocardial analysis. The utilization of the ROC curve allowed us to derive optimal cutoffs, sensibility and specificity for ischemic segments.

Results

The subendocardial analysis at high dose showed to be able to increase significantly the accuracy of the test to detect the ischemic segments (sens 90.2% vs 85.4%; spec 93.1% vs 92.2%). Moreover, at the low dose, the subendocardial analysis showed to be able to increase significantly, mostly the specificity of the test (sens 69.6% vs 68.3%; spec 92.2% vs 86.2%). Notably, the strain subendocardial analysis at low dose showed to reach a high specificity, similar to the peak dose transmural analysis.

Conclusions

Measurement of subendocardial strain during DSE is feasible and can increase the accuracy of the test. Moreover, the subendocardial strain during DSE can reach a high specificity, even limiting the test at a low dose infusion.
Spatial connectedness imposes local‐ and metapopulation‐level selection on life history through feedbacks on demography
Authors: Masier Stefano , Bonte Dries
Published: November 2019

Dispersal evolution impacts the fluxes of individuals and hence, connectivity in metapopulations. Connectivity is therefore decoupled from the structural connectedness of the patches within the spatial network. Because of demographic feedbacks, local selection also drives the evolution of other life history traits. We investigated how different levels of connectedness affect trait evolution in experimental metapopulations of the two‐spotted spider mite. We separated local‐ and metapopulation‐level selection and linked trait divergence to population dynamics. With lower connectedness, an increased starvation resistance and delayed dispersal evolved. Reproductive performance evolved locally by transgenerational plasticity or epigenetic processes. Costs of dispersal, but also changes in local densities and temporal fluctuations herein are found to be putative drivers. In addition to dispersal, demographic traits are able to evolve in response to metapopulation connectedness at both the local and metapopulation level by genetic and/or non‐genetic inheritance. These trait changes impact the persistence of spatially structured populations.
Characteristics and management of the haemophilia‐associated pseudotumours
Authors: Doyle Andrew J. , Back Diane L. , Austin Steve
Published: November 2019

The management of haemophilia‐associated pseudotumours presents an ongoing challenge to the haematologist, surgeon and interventional radiologist alike. There is a range of therapeutic approaches including factor replacement, embolization, radiotherapy and a variety of surgical interventions. However, there remains little evidence regarding the most appropriate treatment. We aimed to evaluate the available options of management for the haemophilia‐associated pseudotumour. A literature review was performed using relevant terminology and reviewed for treatment approaches and outcomes. The results demonstrated that most of the data is from single case reports with a small number of single‐ and multicentre case series. In total, 133 patients with 134 described pseudotumours were identified. Adequate haemostatic control with factor replacement was a key component to successful treatment. Surgical excision was the most commonly reported surgical intervention with various composites used for filling of the surgical cavity. The use of radiotherapy has been described particularly in the paediatric population and sites of difficult surgical access. Embolization can be considered as a method of presurgical optimization. Patients with both factor inhibitors and pseudotumours have poorer postoperative outcomes. This review demonstrates that although a lack of large‐centre, randomized studies, timely surgical intervention with adequate haemostatic support and the consideration adjuvant therapies in selected cases can achieve acceptable outcomes in this cohort of patients.
Expanding the spectrum of chronic necrotising (semi‐invasive) aspergillosis: a series of eight cases presenting as radiologically solid lung nodules mimicking malignancy
Authors: Dermawan Josephine K , Ghosh Subha , Mukhopadhyay Sanjay
Published: November 2019

Aim

To clinicopathologically characterise a subset of aspergillosis cases characterised by radiologically solid lung nodules.

Methods and results

We reviewed our archives for lung biopsies/resections with fungal hyphae on histology. Cases classifiable as a well‐established form of aspergillosis were excluded. Unclassifiable cases with radiologically solid lung nodules and histological evidence of fungal hyphae consistent with Aspergillus were analysed in detail. Of 134 lung biopsies/resections with fungal hyphae, eight presented as a solid lung nodule on imaging and could not be classified as a well‐recognised form of aspergillosis. All patients were non‐immunocompromised/minimally immunocompromised adult smokers. Imaging showed solid, predominantly solitary, spiculated, subpleural, hypermetabolic upper lobe nodules in emphysematous lungs. Malignancy was suspected clinically in all cases. Histologically, the nodules were necrotising granulomas containing fungal hyphae consistent with Aspergillus. On follow‐up, none of the nodules recurred or progressed to invasive disease.

Conclusions

Aspergillosis can present as a radiologically solid, spiculated lung nodule suspicious for malignancy.
Hospital safety climate from nurses’ perspective in four European countries
Authors: Gurková E. , Zeleníková R. , Friganovic A. , Uchmanowicz I. , Jarošová D. , Papastavrou E. , Žiaková K.
Published: November 2019

Background

Nursing shortages, the substitution of practical nurses for registered nurses, an ageing workforce, the decreasing number of nurse graduates and the increasing migration of young nurses are important factors associated with the hospital safety climate in Central European countries.

Aims

The aim of the study was to investigate nurses’ perceptions of the safety climate in four selected central European countries (Croatia, the Czech Republic, Poland and Slovakia) and to determine the relationship between safety climate and unfinished nursing care.

Methods

A cross‐sectional study was used. The sample consisted of 1353 European nurses from four countries. Instruments used were the Hospital Survey on Patient Safety Culture and the Perceived Implicit Rationing of Nursing Care. Data were analysed using descriptive statistics and multiple regression analyses.

Results

Significant differences were found between countries in all unit/hospital/outcome dimensions. ‘Perceived Patient Safety’ and ‘Reporting of Incident Data’ were associated with aspects of ‘Organizational Learning’ and ‘Feedback and Communication about Error’. Higher prevalence of unfinished nursing care is associated with more negative perceptions of patient safety climate.

Conclusions

Cross‐cultural comparisons allow us to examine differences and similarities in safety dimensions across countries. The areas with potential for initiating strategies for improvement in all four countries are ‘Staffing’, ‘Non‐punitive Response to Error’ and ‘Teamwork across Hospital Units’.

Implications for nursing and health policy

‘Feedback and Communicating about Error’ and ‘Organizational Learning ‐ Continuous Improvement’ were the main predictors of ‘Overall Perception of Patient Safety’ and ‘Reporting of Incident Data’. Therefore, nurse managers should focus on how to empower nurses in these areas in order to foster a no‐blame culture and effective reporting. In addition, it is important for policymakers to update nursing education standards in order to address patient safety.
Measurement of stress build‐up of ion exchange strengthened lithium aluminosilicate glass
Authors: Hödemann Siim , Valdmann Andreas , Paemurru Mart , Anton Johan , Kiisk Valter , Tkaczyk Eric , Kikas Jaak
Published: November 2019

A recently developed nondestructive method was used to investigate the stress build‐up in chemically strengthened lithium aluminosilicate glass. We utilized an updated version of the gradient scattered light method, which now enables more precise determination of the depth coordinates, recovering a more detailed stress profile around the knee. The main motivation of the work was to characterize and optimize the development of the knee‐shaped breaking point in stress profile in lithium aluminosilicate glass prepared by the Saunders‐Kubichan method of one‐step strengthening in a mixture of KNO3+NaNO3 molten salt bath. In the industry, a two‐step process is still commonly used to build such a stress profile; the one‐step strengthening will simplify the process as well as save the cost. Compared to previous studies, which used a destructive method based on transmitted light photoelasticity, we found that in the samples ion exchanged for 24 hours, the knee‐shaped breaking points were situated two times deeper whereas the case depths were 28% shallower. The measured stress profiles were validated by stress equilibrium and by comparison to Na+ ion concentration profiles.