bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmission and evolution of OXA-48-producing Klebsiella pneumoniae ST11 in a single hospital in Taiwan
Authors: Lu Min-Chi , Chen Ying-Tsong , Tang Hui-Ling , Liu Yen-Yi , Chen Bo-Han , Wang You-Wun , Chen Yi-Syong , Teng Ru-Hsiou , Hong Yu-Ping , Chiou Chien-Shun , Chiang Ming-Ko , Lai Yi-Chyi
Published: October 2019

Objectives

Epidemic spread of OXA-48-producing Klebsiella pneumoniae, mainly mediated by the transmission of a blaOXA-48-carrying plasmid, has threatened global health during the last decade. Since its introduction to Taiwan in 2013, OXA-48 has become the second most common carbapenemase. We described the transmission and evolution of an OXA-producing K. pneumoniae clone in a single hospital.

Methods

Twenty-two OXA-48 K. pneumoniae were isolated between October 2013 and December 2015. Comparative genomic analysis was performed based on the WGS data generated with Illumina and MinION techniques.

Results

Seventeen of the 22 OXA-48 K. pneumoniae that belonged to ST11, with the same capsular genotype, KL64, and differed from each other by seven or fewer SNPs, were considered outbreak strains. Eight of the 17 outbreak strains harboured a 65 499 bp blaOXA-48-carrying IncL plasmid (called pOXA48). pOXA48 was absent from the remaining nine strains. Instead, a 24.9 kb blaOXA-48-carrying plasmid fragment was integrated into a prophage region of their chromosomes. Transmission routes of the ST11_KL64 K. pneumoniae sublineages, which carried either pOXA48 or chromosomally integrated blaOXA-48, were reconstructed.

Conclusions

Clonal expansion of ST11_KL64 sublineages contributed to the nosocomial outbreak of OXA-48 K. pneumoniae. The chromosome-borne blaOXA-48 lineage emerged during a 2 year period in a single hospital. Dissemination of OXA-48, which is vertically transmitted in K. pneumoniae even in the absence of selective pressure from antimicrobials, deserves public health attention.
The impact of drug order complexity on prospective medication order review and verification time
Authors: Dakwa David S , Marshall Vincent D , Chaffee Bruce W
Published: October 2019

Objective

To assess if the amount of time a pharmacist spends verifying medication orders increases as medication orders become more complex.

Materials and Methods

The study was conducted by observing pharmacist verification of adult medication orders in an academic medical center. Drug order complexity was prospectively defined and validated using a classification system derived from 3 factors: the degree of order variability, ISMP high-alert classification, and a pharmacist perception survey. Screen capture software was used to measure pharmacist order review time for each classification. The annualized volume of low complexity drug orders was used to calculate the potential time savings if these were verified using an alternate system that did not require pharmacist review.

Results

The primary study hypothesis was not achieved. Regression results did not show statistical significance for moderate (n = 30, 23.7 seconds, sd = 23.3) or high complexity (n = 30, 18.6 seconds, sd = 23.1) drugs relative to the low complexity drugs (n = 30, 8.0 seconds, sd = 14.4) nor for moderate vs high complexity; (βmoderate vs low = 15.6, P = .113), (βhigh vs low = 10.3, P = .235), (βmoderate vs high = 5.3, P = .737). The sensitivity analysis showed statistical significance in the high vs low comparison (βhigh vs low = 13.8, P = .017).

Discussion

This study showed that verifying pharmacists spent less time than projected to verify medication orders of different complexities, but the time did not correlate with the classifications used in our complexity scale. Several mitigating factors, including operational aspects associated with timing antimicrobial orders, likely influenced order verification time. These factors should be evaluated in future studies which seek to define drug order complexity and optimize pharmacist time spent in medication order verification.

Conclusion

The findings suggest that there may be other factors involved in pharmacist decision-making that should be considered when categorizing drugs by perceived complexity.
Loxodonta Localizer: A Software Tool for Inferring the Provenance of African Elephants and Their Ivory Using Mitochondrial DNA
Authors: Zhao Kai , Ishida Yasuko , Green Cory E , Davidson Alexis G , Sitam Frankie A T , Donnelly Cassidy L , De Flamingh Alida , Perrin-Stowe Tolulope I N , Bourgeois Stéphanie , Brandt Adam L , Mundis Stephanie J , Van Aarde Rudi J , Greenberg Jonathan A , Malhi Ripan S , Georgiadis Nicholas J , Mcewing Ross , Roca Alfred L
Published: October 2019

Illegal hunting is a major threat to the elephants of Africa, with more elephants killed by poachers than die from natural causes. DNA from tusks has been used to infer the source populations for confiscated ivory, relying on nuclear genetic markers. However, mitochondrial DNA (mtDNA) sequences can also provide information on the geographic origins of elephants due to female elephant philopatry. Here, we introduce the Loxodonta Localizer (LL; www.loxodontalocalizer.org), an interactive software tool that uses a database of mtDNA sequences compiled from previously published studies to provide information on the potential provenance of confiscated ivory. A 316 bp control region sequence, which can be readily generated from DNA extracted from ivory, is used as a query. The software generates a listing of haplotypes reported among 1917 African elephants in 24 range countries, sorted in order of similarity to the query sequence. The African locations from which haplotype sequences have been previously reported are shown on a map. We demonstrate examples of haplotypes reported from only a single locality or country, examine the utility of the program in identifying elephants from countries with varying degrees of sampling, and analyze batches of confiscated ivory. The LL allows for the source of confiscated ivory to be assessed within days, using widely available molecular methods that do not depend on a particular platform or laboratory. The program enables identification of potential regions or localities from which elephants are being poached, with capacity for rapid identification of populations newly or consistently targeted by poachers.
Pathocentric Health Care and a Minimal Internal Morality of Medicine
Authors: Hershenov David B
Published: October 2019

Christopher Boorse is very skeptical of there being a pathocentric internal morality of medicine. Boorse argues that doctors have always engaged in activities other than healing, and so no internal morality of medicine can provide objections to euthanasia, contraception, sterilization, and other practices not aimed at fighting pathologies. Objections to these activities have to come from outside of medicine. I first argue that Boorse fails to appreciate that such widespread practices are compatible with medicine being essentially pathocentric. Then I contend that the pathocentric essence, properly understood, does not prohibit physicians from engaging in actions that are not aimed at combating pathologies, but rather supports an internal morality of medicine that allows medical providers to refuse without penalty to engage in practices that promote pathologies.
Learning from Performance Information
Authors: Andersen Simon Calmar , Nielsen Helena Skyt
Published: October 2019

Years of research on performance management has generally concluded that performance information is seldom used purposefully by public managers and that it does not improve performance as intended. More recently, both theoretical and empirical work have begun to focus on situations in which performance management may facilitate internal organizational learning. In this study, we focus on one key component in performance management systems, namely generation of performance information. Based on a Bayesian learning model, we argue that generation of performance information at the individual level may create performance improvements because both users and frontline workers may learn where to prioritize their efforts. To test the isolated effect of this key component of any performance management system, we use as-good-as-random variation in exposure of students to testing because of a technical breakdown in an IT system. We identify the effect of testing on student learning measured two years after the breakdown. Results show positive and statistically significant effects of about 0.1 standard deviations, which is comparable to much more expensive interventions, and effects tend to persist after four years. We find larger effects for students with low socioeconomic status but also that schools with many students from this group are more reluctant to measure their performance. Implications and limitations in terms of increasing the level of student testing are discussed.
Topical Review: State of the Field of Child Self-Report of Acute Pain
Authors: Cohen Lindsey L , Donati Matthew R , Shih Sharon , Sil Soumitri
Published: October 2019

Objective

Children experience acute pain with routine and emergent healthcare, and untreated pain can lead to a range of repercussions. Assessment is vital to diagnosing and treating acute pain. Given the internal nature of pain, self-report is predominant. This topical review reflects on the state of the field of pediatric acute pain self-report, and proposes a framework for acute pain assessment via self-report.

Method

We examine self-report of acute pain in preschool-age children through adolescents, and we detail a three-step process to optimize acute pain assessment.

Results

The first step is to decide between a pain screening or assessment. Several 0–10 self-report scales are available for pain screenings. Assessment requires specification of the goals and domains to target. Core criteria, common features, modulating factors, and consequences of acute pain provide a framework for a comprehensive pain assessment. Whereas there are some measures available to assess aspects of these domains, there are considerable gaps. Last, it is important to integrate the data to guide clinical care of acute pain.

Conclusions

Self-report of acute pain is dominated by single-item intensity scales, which are useful for pain screening but inadequate for pain assessment. We propose a three-step approach to acute pain assessment in children. However, there is a need for measure development for a comprehensive evaluation of the core criteria, common features, modulating factors, and consequences of pediatric acute pain. In addition, there is limited guidance in merging data found in multifaceted evaluations of pediatric acute pain.
Psychosocial Interventions Targeting Recovery in Child and Adolescent Burns: A Systematic Review
Authors: Hornsby Nancy , Blom Lisa , Sengoelge Mathilde
Published: October 2019

Children post-burn injury experience a range of psychosocial sequelae that benefit from early provision of psychosocial support. However, no systematic review exists evaluating the full range of psychological interventions.

Objective

To critically evaluate psychosocial interventions for children (<18 years old) with burn injuries in improving psychosocial recovery.

Study design

All-language studies were identified from inception to March 2018 in six electronic databases and appraised according to PRISMA checklist and Cochrane Risk of Bias Tool for quality. Studies were stratified into three groups: distraction (virtual reality, child life therapy, imagery-based therapy, hypnosis), burn camps, and other (social skills, cognitive behavioral therapy, parent group counseling).

Results

Out of a total of 5,456 articles identified, 297 underwent full review resulting in 27 included articles published between 1986 and 2018. Sample sizes ranged from 9 to 266, comprising child and adult participants. A range of interventions and psychosocial outcome measures were found. Several studies (n = 21) reported statistically significant improvements in outcome; the majority were distraction interventions to reduce pain and anxiety. A limited number of studies showing effect was found for cognitive behavioral therapy and parent counseling. Risk of bias was high in studies of burn camps and mixed for all other interventions.

Conclusions

A range of psychosocial interventions and outcome tools exist in pediatric burns. Distraction interventions prior to and/or during dressing changes or physical therapy were shown to effectively reduce pain and anxiety for a wide range of pediatric ages.
Safety and Varicella Outcomes in In Utero–Exposed Newborns and Preterm Infants Treated With Varicella Zoster Immune Globulin (VARIZIG): A Subgroup Analysis of an Expanded-Access Program
Authors: Duchon Jennifer M , Levin Myron J , Gershon Anne A
Published: October 2019

Background

Infants exposed to varicella zoster virus (VZV) in utero ≤5 days before or ≤48 hours after delivery and preterm infants are at high risk for varicella complications. An expanded-access program assessed varicella outcomes after administration of varicella zoster immune globulin (human) (VARIZIG) in a real-world setting.

Methods

In this open-label, expanded-access program, high-risk infants received ≤125 IU/10 kg of VARIZIG (NCT00338442). VZV outcomes and safety were assessed.

Results

There were 43 newborns exposed to VZV in utero and 80 preterm infants exposed to VZV; >80% received VARIZIG within 96 hours of reported exposure. When varicella outcomes were available, varicella occurred in 7 of 38 (18%) in utero–exposed newborns and zero of 65 preterm infants. Varicella-related complications were reported in 3 in utero–exposed newborns (3 with >100 lesions, 1 each with encephalitis and pneumonia). Adverse events were reported for 16% of in utero–exposed newborns and 25% of preterm infants, but few were considered related to VARIZIG. There were no deaths attributable to varicella or VARIZIG.

Conclusions

Varicella incidence and morbidity were low in in utero–exposed infants and zero in preterm infants who received prophylactic VARIZIG. There were few VARIZIG-related safety concerns.
Fracture of a popliteal nitinol stent and pseudoaneurysm: a case report and review of the literature
Authors: Reis José Maciel Caldas dos , Kudo Fábio Akimaro , Carmo Bastos Moisés do
Published: October 2019

There is a lack of reports onr stent fracture with pseudoaneurysm formation in the femoropopliteal artery, which can cause restenosis or occlusion of the treated arterial segment. We present a case of a large pseudoaneurysm of the popliteal artery that was observed 18 months after popliteal stenting using a self-expandable nitinol stent. We describe an endovascular approach to overcome this severe complication. Stent fractures are an often overlooked complication of femoropopliteal stenting and can be associated with serious diseases. The popliteal artery was successfully treated using self-expandable Viabahn endoprosthesis.
The Speaker-Oriented Connective Particle ‘Al-Kēn in 2 SAM. 7:22
Authors: Tsumura D T
Published: October 2019

The connective particle ‘al-kēn ‘therefore’ usually functions to intro-duce a logical conclusion or consequence: ‘A therefore B’. However, in cases such as 2 Sam 7:22 it functions as a speaker-oriented particle — what is mentioned in the preceding verse is the reason why the speaker makes the following statement. This usage may be compared with another speaker-oriented particle kî ‘for’, which explains the reason for the speaker's previous utterance. These two speaker-oriented particles may be explained thus:

speaker-oriented kî:   ‘This (B) is the reason why I said that (A)’

speaker-oriented ‘al-kēn:  ‘That (A) is the reason why I say this (B)’
T2Candida magnetic resonance in patients with invasive candidiasis: Strengths and limitations
Authors: Zurl Christoph , Prattes Juergen , Zollner-Schwetz Ines , Valentin Thomas , Rabensteiner Jasmin , Wunsch Stefanie , Hoenigl Martin , Krause Robert
Published: October 2019

T2Candida enables detection of five Candida species in whole blood within approximately 5 hours. Routinely drawn EDTA blood samples were prospectively stored and tested with T2Candida in patients with invasive candidiasis identified by routine index blood or sterile site cultures. T2Candida was compared to diagnostic blood and sterile site cultures and also performed with samples obtained prior and after collection of index cultures. T2Candida was evaluated with 133 samples of 32 patients with candidemia and 22 patients with deep-seated invasive candidiasis. In the candidemic group 28/32 (87.5%) patients had at least one positive T2Candida result at any time point. A total of 17/25 (68%) candidemic patients had a positive T2Candida sample that was drawn concurrently to the index blood culture. In the per patient analysis 17/18 (94.4%) candidemic patients with matched T2Candida samples and peripheral blood cultures at any timepoint had a positive T2Candida test. T2Candida revealed discordant Candida species identification in two candidemic patients. Six of 22 (27.3%) deep-seated IC patients had a positive T2Candida result. Despite advanced time-to-results the clinical value of T2Candida in diagnosing candidemia seems to be limited by missing blood culture positive cases. Positivity rates of T2Candida increased when serial T2Candida samples were tested. In patients with suspected deep-seated invasive candidiasis T2Candida might act as a blood based adjunct to sterile site cultures.
The dynamical Roche lobe in hierarchical triples
Authors: Di Stefano Rosanne
Published: October 2019

The Roche lobe formalism describes mass transfer from one star to another. We develop an extension to hierarchical triples, considering the case in which a star donates mass to a companion which is itself a binary. The L1 point moves as the inner binary rotates, and the Roche lobe pulsates with the period of the inner binary. Signatures of mass transfer may therefore be imprinted with the orbital period of the inner binary. For some system parameters, the pulsing Roche lobe can drive mass transfer at high rates. Systems undergoing this type of mass transfer include those with inner binaries consisting of compact objects that will eventually merge, as well as progenitors of Type Ia supernovae.
Laboratory study on the fullerene–PAH-derived cluster cations in the gas phase
Authors: Zhen Junfeng , Zhang Weiwei , Yang Yuanyuan , Zhu Qingfeng
Published: October 2019

It is possible that fullerene–polycyclic aromatic hydrocarbon (PAH) clusters or associations of fullerenes with PAHs contain a large fraction of interstellar fullerenes in the interstellar medium. Herein, we report the formation and photofragmentation behaviour of fullerene–PAH derivatives, fullerene/9-vinylanthracene (C16H12) and fullerene/9-methylanthracene (C15H12) cluster cations. Experiments are carried out using a quadrupole ion trap in combination with time-of-flight mass spectrometry in the gas phase. The results show that fullerene (C60)/9-vinylanthracene (e.g. [(C16H12)3C60]+), fullerene (C56 and C58)/9-vinylanthracene (e.g. [(C16H12)4C56]+ and [(C16H12)4C58]+), fullerene (C60)/9-methylanthracene (e.g. [(C15H12)3C60]+), and fullerene (C56 and C58)/9-methylanthracene (e.g. [(C15H12)4C56]+ and [(C15H12)4C58]+) cluster cations, i.e. large fullerene-derived molecules, are formed in the gas phase through the ion–molecule reaction pathway. With irradiation, all fullerene–PAH-derived cluster cations lose their monomolecular groups without other fragmentation channels (e.g. dehydrogenation). The structure of newly formed fullerene–PAH-derived cluster cations and the bond energy for these adduction formation pathways are investigated with theoretical calculations.

The obtained results provide a general molecular growth route towards large fullerene–PAH derivatives (e.g. large fullerene-derived molecules) with functional PAHs in a bottom-up formation process and insights into the effect of functional groups (e.g. vinyl, –C2H3, and methyl, –CH3) on their formation and photoevolution behaviours. In addition, the fullerene–PAH-derived clusters (from 83 to 170 atoms in total, or ∼2 nm in size) offer a good model of carbon dust grains, and the relevance to the nanometre-sized carbon dust grain in space is briefly discussed.
The dust mass function from z ∼0 to z ∼2.5
Authors: Pozzi F , Calura F , Zamorani G , Delvecchio I , Gruppioni C , Santini P
Published: October 2019

We derive for the first time the dust mass function (DMF) in a wide redshift range, from z ∼ 0.2 up to z ∼ 2.5. In order to trace the dust emission, we start from a far-IR (160-μm) Herschel selected catalogue in the COSMOS field. We estimate the dust masses by fitting the far-IR data (λrest$\,\, \buildrel\gt \over \sim \,\,$50 μm) with a modified black body function and we present a detailed analysis to take into account the incompleteness in dust masses from a far-IR perspective. By parametrizing the observed DMF with a Schechter function in the redshift range 0.1 < z ≤ 0.25, where we are able to sample faint dust masses, we measure a steep slope (α ∼1.48), as found by the majority of works in the Local Universe. We detect a strong dust mass evolution, with $M_{\rm d}^{\star }$ at z ∼ 2.5 almost 1 dex larger than in the local Universe, combined with a decrease in their number density. Integrating our DMFs, we estimate the dust mass density (DMD), finding a broad peak at z ∼ 1, with a decrease by a factor of ∼ 3 towards z ∼ 0 and z ∼ 2.5. In general, the trend found for the DMD mostly agrees with the derivation of Driver et al., another DMD determination based also on far-IR detections, and with other measures based on indirect tracers.
Young stars raining through the galactic halo: the nature and orbit of price-whelan 1
Authors: Bellazzini Michele , Ibata Rodrigo A , Martin Nicolas , Malhan Khyati , Marasco Antonino , Famaey Benoit
Published: October 2019

We present radial velocities for five member stars of the recently discovered young (age ≃ 100−150 Myr) stellar system Price-Whelan 1 (PW 1), which is located far away in the Galactic Halo (D≃ 29 kpc, Z≃ 15 kpc), and that is probably associated with the leading arm (LA) of the Magellanic Stream. We measure the systemic radial velocity of PW 1, Vr = 275 ± 10 km s−1, significantly larger than the velocity of the LA gas in the same direction. We re-discuss the main properties and the origin of this system in the light of these new observations, computing the orbit of the system and comparing its velocity with that of the H i in its surroundings. We show that the bulk of the gas at the velocity of the stars is more than 10 deg (5 kpc) away from PW 1 and the velocity difference between the gas and the stars becomes larger as gas closer to the stars is considered. We discuss the possibilities that (1) the parent gas cloud was dissolved by the interaction with the Galactic gas, and (2) that the parent cloud is the high-velocity cloud (HVC) 287.5+22.5 + 240, lagging behind the stellar system by ≃ 25 km s−1 and ≃10 deg ≃ 5 kpc. This HVC, which is part of the LA, has metallicity similar to PW 1, displays a strong magnetic field that should help to stabilize the cloud against ram pressure, and shows traces of molecular hydrogen. We also show that the system is constituted of three distinct pieces that do not differ only by position in the sky but also by stellar content.
An optimised STAPUT method for the purification of mouse spermatocyte and spermatid populations
Authors: Dunleavy Jessica E M , O’Connor Anne E , O’Bryan Moira K
Published: October 2019

The purification of individual male germ cell populations is integral for the molecular and biochemical characterisation of specific spermatogenic phases. Although a number of more contemporary techniques have been developed, velocity sedimentation using the STAPUT method remains as a gold standard for this purpose. The gentle nature of the technique, wherein germ cell subpopulations are separated by sedimentation at unit gravity, results in the isolation of viable and high-purity cells. We provide an updated and simplified step-by-step version of the STAPUT protocol for the purification of mouse male germ cells. As per the original method, the protocol described herein allows for the purification of mouse spermatocyte and round spermatids, however it also allows for successful purification of elongating, and elongated spermatid populations, and is optimised for the preservation of cellular ultrastructure. This method yields sufficient numbers of high-purity cells from one adult mouse for RNA or protein extraction or for immunolocalisation studies.
Genus for biomolecules
Authors: Rubach Paweł , Zajac Sebastian , Jastrzebski Borys , Sulkowska Joanna I , Sułkowski Piotr
Published: October 2019

The ‘Genus for biomolecules’ database (http://genus.fuw.edu.pl) collects information about topological structure and complexity of proteins and RNA chains, which is captured by the genus of a given chain and its subchains. For each biomolecule, this information is shown in the form of a genus trace plot, as well as a genus matrix diagram. We assemble such information for all and RNA structures deposited in the Protein Data Bank (PDB). This database presents also various statistics and extensive information about the biological function of the analyzed biomolecules. The database is regularly self-updating, once new structures are deposited in the PDB. Moreover, users can analyze their own structures.
Click-encoded rolling FISH for visualizing single-cell RNA polyadenylation and structures
Authors: Chen Feng , Bai Min , Cao Xiaowen , Zhao Yue , Xue Jing , Zhao Yongxi
Published: October 2019

Spatially resolved visualization of RNA processing and structures is important for better studying single-cell RNA function and landscape. However, currently available RNA imaging methods are limited to sequence analysis, and not capable of identifying RNA processing events and structures. Here, we developed click-encoded rolling FISH (ClickerFISH) for visualizing RNA polyadenylation and structures in single cells. In ClickerFISH, RNA 3′ polyadenylation tails, single-stranded and duplex regions are chemically labeled with different clickable DNA barcodes. These barcodes then initiate DNA rolling amplification, generating repetitive templates for FISH to image their subcellular distributions. Combined with single-molecule FISH, the proposed strategy can also obtain quantitative information of RNA of interest. Finally, we found that RNA poly(A) tailing and higher-order structures are spatially organized in a cell type-specific style with cell-to-cell heterogeneity. We also explored their spatiotemporal patterns during cell cycle stages, and revealed the highly dynamic organization especially in S phase. This method will help clarify the spatiotemporal architecture of RNA polyadenylation and structures.
Structure of tRNA methyltransferase complex of Trm7 and Trm734 reveals a novel binding interface for tRNA recognition
Authors: Hirata Akira , Okada Keisuke , Yoshii Kazuaki , Shiraishi Hiroyuki , Saijo Shinya , Yonezawa Kento , Shimizu Nobutaka , Hori Hiroyuki
Published: October 2019

The complex between Trm7 and Trm734 (Trm7–Trm734) from Saccharomyces cerevisiae catalyzes 2′-O-methylation at position 34 in tRNA. We report biochemical and structural studies of the Trm7–Trm734 complex. Purified recombinant Trm7–Trm734 preferentially methylates tRNAPhe transcript variants possessing two of three factors (Cm32, m1G37 and pyrimidine34). Therefore, tRNAPhe, tRNATrp and tRNALeu are specifically methylated by Trm7–Trm734. We have solved the crystal structures of the apo and S-adenosyl-L-methionine bound forms of Trm7–Trm734. Small angle X-ray scattering reveals that Trm7–Trm734 exists as a hetero-dimer in solution. Trm7 possesses a Rossmann-fold catalytic domain, while Trm734 consists of three WD40 β-propeller domains (termed BPA, BPB and BPC). BPA and BPC form a unique V-shaped cleft, which docks to Trm7. The C-terminal region of Trm7 is required for binding to Trm734. The D-arm of substrate tRNA is required for methylation by Trm7–Trm734. If the D-arm in tRNAPhe is docked onto the positively charged area of BPB in Trm734, the anticodon-loop is located near the catalytic pocket of Trm7. This model suggests that Trm734 is required for correct positioning of tRNA for methylation. Additionally, a point-mutation in Trm7, which is observed in FTSJ1 (human Trm7 ortholog) of nosyndromic X-linked intellectual disability patients, decreases the methylation activity.
GWAS Central: a comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies
Authors: Beck Tim , Shorter Tom , Brookes Anthony J
Published: October 2019

The GWAS Central resource provides a toolkit for integrative access and visualization of a uniquely extensive collection of genome-wide association study data, while ensuring safe open access to prevent research participant identification. GWAS Central is the world's most comprehensive openly accessible repository of summary-level GWAS association information, providing over 70 million P-values for over 3800 studies investigating over 1400 unique phenotypes. The database content comprises direct submissions received from GWAS authors and consortia, in addition to actively gathered data sets from various public sources. GWAS data are discoverable from the perspective of genetic markers, genes, genome regions or phenotypes, via graphical visualizations and detailed downloadable data reports. Tested genetic markers and relevant genomic features can be visually interrogated across up to sixteen multiple association data sets in a single view using the integrated genome browser. The semantic standardization of phenotype descriptions with Medical Subject Headings and the Human Phenotype Ontology allows the precise identification of genetic variants associated with diseases, phenotypes and traits of interest. Harmonization of the phenotype descriptions used across several GWAS-related resources has extended the phenotype search capabilities to enable cross-database study discovery using a range of ontologies. GWAS Central is updated regularly and available at https://www.gwascentral.org.
Mutations of R882 change flanking sequence preferences of the DNA methyltransferase DNMT3A and cellular methylation patterns
Authors: Emperle Max , Adam Sabrina , Kunert Stefan , Dukatz Michael , Baude Annika , Plass Christoph , Rathert Philipp , Bashtrykov Pavel , Jeltsch Albert
Published: October 2019

Somatic DNMT3A mutations at R882 are frequently observed in AML patients including the very abundant R882H, but also R882C, R882P and R882S. Using deep enzymology, we show here that DNMT3A-R882H has more than 70-fold altered flanking sequence preferences when compared with wildtype DNMT3A. The R882H flanking sequence preferences mainly differ on the 3′ side of the CpG site, where they resemble DNMT3B, while 5′ flanking sequence preferences resemble wildtype DNMT3A, indicating that R882H behaves like a DNMT3A/DNMT3B chimera. Investigation of the activity and flanking sequence preferences of other mutations of R882 revealed that they cause similar effects. Bioinformatic analyses of genomic methylation patterns focusing on flanking sequence effects after expression of wildtype DNMT3A and R882H in human cells revealed that genomic methylation patterns reflect the details of the altered flanking sequence preferences of R882H. Concordantly, R882H specific hypermethylation in AML patients was strongly correlated with the R882H flanking sequence preferences. R882H specific DNA hypermethylation events in AML patients were accompanied by R882H specific mis-regulation of several genes with strong cancer connection, which are potential downstream targets of R882H. In conclusion, our data provide novel and detailed mechanistic understanding of the pathogenic mechanism of the DNMT3A R882H somatic cancer mutation.
Survival of patients treated with extended-hours haemodialysis in Europe: an analysis of the ERA-EDTA Registry
Authors: Jansz Thijs T , Noordzij Marlies , Kramer Anneke , Laruelle Eric , Couchoud Cécile , Collart Frederic , Cases Aleix , Arici Mustafa , Helve Jaako , Waldum-Grevbo Bård , Rydell Helena , Traynor Jamie P , Zoccali Carmine , Massy Ziad A , Jager Kitty J , van Jaarsveld Brigit C
Published: October 2019

Background

Previous US studies have indicated that haemodialysis with ≥6-h sessions [extended-hours haemodialysis (EHD)] may improve patient survival. However, patient characteristics and treatment practices vary between the USA and Europe. We therefore investigated the effect of EHD three times weekly on survival compared with conventional haemodialysis (CHD) among European patients.

Methods

We included patients who were treated with haemodialysis between 2010 and 2017 from eight countries providing data to the European Renal Association–European Dialysis and Transplant Association Registry. Haemodialysis session duration and frequency were recorded once every year or at every change of haemodialysis prescription and were categorized into three groups: CHD (three times weekly, 3.5–4 h/treatment), EHD (three times weekly, ≥6 h/treatment) or other. In the primary analyses we attributed death to the treatment at the time of death and in secondary analyses to EHD if ever initiated. We compared mortality risk for EHD to CHD with causal inference from marginal structural models, using Cox proportional hazards models weighted for the inverse probability of treatment and censoring and adjusted for potential confounders.

Results

From a total of 142 460 patients, 1338 patients were ever treated with EHD (three times, 7.1 ± 0.8 h/week) and 89 819 patients were treated exclusively with CHD (three times, 3.9 ± 0.2 h/week). Crude mortality rates were 6.0 and 13.5/100 person-years. In the primary analyses, patients treated with EHD had an adjusted hazard ratio (HR) of 0.73 [95% confidence interval (CI) 0.62–0.85] compared with patients treated with CHD. When we attributed all deaths to EHD after initiation, the HR for EHD was comparable to the primary analyses [HR 0.80 (95% CI 0.71–0.90)].

Conclusions

EHD is associated with better survival in European patients treated with haemodialysis three times weekly.
Incidence, prognostic impact and clinical outcomes of renal impairment in patients with multiple myeloma: a population-based registry
Authors: Courant Maxime , Orazio Sebastien , Monnereau Alain , Preterre Julie , Combe Christian , Rigothier Claire
Published: October 2019

Background

Renal impairment (RI), a severe complication in multiple myeloma (MM), is considered as a poor prognostic factor. Patient survival has increased with the use of novel drugs and autologous stem-cell transplantation (ASCT). However, specific evolution of the incidence of RI in MM and its impact on prognosis remain unclear.

Methods

Using a population-based registry of 1038 newly diagnosed MM in Gironde, France, we evaluated the incidence trends of RI in MM patients and assessed net survival according to factors of interest using Pohar-Perme indicator and excess mortality rate regression. We also reviewed 114 cases of MM with RI to describe their clinical outcomes.

Results

In our population-based study, 24.6% of MM patients presented with RI (12.9% required haemodialysis). Median survival time was 21 months in patients with RI versus not reached at 3 years for other patients (P < 0.01). Age >73 years, RI, comorbidities and non-use of drugs or ASCT were associated with excess mortality risk. The effect of RI on excess mortality rates was maximum in the first 6 months after diagnosis. In the observational study, median follow-up time was 22.5 months; factors associated with renal response were haematologic response [odds ratio (OR) 6.81; P < 0.01] and previous chronic kidney disease (OR 0.26; P = 0.04). Factors associated with 1-year overall survival were haematological [hazard ratio (HR) 0.13; P < 0.01] and renal response (HR 0.27; P = 0.03).

Conclusions

RI represents an independent negative prognostic factor in MM in the first 6 months after diagnosis. Renal recovery and haematologic response are the strongest markers associated with patient survival.
No mere tautology: the division of labour is limited by the division of labour
Authors: Smyth Andrew , Wilson Bart J
Published: October 2019

We explore the intersection of growth theory and the theory of the firm with an experiment. Economic growth is possible in our experiment when agents specialize to exploit increasing returns. We find that low opportunity costs are sufficient for Marshallian internal economies, but that Marshallian external economies are slow to emerge in four probing treatment conditions. Transaction costs do not hamper external economies as we anticipated prior to collecting data. When external economies falter, it is because new ideas of more extensive specialization fail to emerge. Ideas make further divisions of the division of labour—and thus economic growth—possible. Conversely, a lack of ideas make further divisions of labour and economic growth impossible. Our data reveal how the likelihood of new ideas is inseparably tied to the existing extent of specialization.
“It Hurts as If…”: Pain-Associated Language, Visual Characterization, and Storytelling in Hmong Adults
Authors: Lor Maichou , Vang Xia , Rabago David , Brown Roger L , Backonja Miroslav
Published: October 2019

Objective

Pain is challenging to diagnose and manage in primary care, especially when patients have limited English proficiency (LEP). Little is known about whether LEP patients can provide pain information that is consistent with the process and the content that providers expect in a clinical interaction. We explore how LEP Hmong patients communicate their pain to providers in primary care settings.

Methods

A qualitative study with 67 Hmong participants (63% female and x̄ age = 53.7 years) were recruited from a Midwestern state. Semistructured interviews on pain communication were conducted, audio-recorded, transcribed, and analyzed using directed content analysis.

Results

The Hmong participants described pain using stories that generally had the same dimensions of information that providers require for pain assessment. These included references to time, causality, associated symptoms or related experiences, intensity, and consequences of pain. However, the participants expressed some pain dimensions in language that was not shared by providers: visual metaphors that were generally in reference to pain quality and fewer words for pain location, intensity, and some qualities. Participants used two strategies to decide whether they should tell their pain story: assessing the provider and determining whether their story was appreciated. The perception that providers underappreciated their stories resulted in dissatisfaction and undertreatment of pain. Ultimately, this resulted in having less frequent contact with providers or changing providers.

Conclusions

Findings demonstrate a discordance in the expected process and content of the clinical interaction between LEP Hmong patients and providers, suggesting the need for culturally appropriate pain assessments in this population.
Predicting Success for Student Physical Therapists on the National Physical Therapy Examination: Systematic Review and Meta-Analysis
Authors: Wolden Mitch , Hill Brent , Voorhees Sara
Published: October 2019

Background

In physical therapist education, the National Physical Therapy Examination (NPTE) is the predominant measure of student success. Because the NPTE is a high-stakes examination, predicting NPTE performance is important for physical therapist students and programs.

Purpose

The purpose of this study was to determine the relationships between first attempt NPTE performance, physical therapist applicant variables, and physical therapist student variables. The 4 identified physical therapist applicant variables were undergraduate cumulative grade point average (GPA), undergraduate GPA for prerequisite courses, Graduate Record Examination verbal and quantitative subscale scores, and admission scores. The 4 identified physical therapist student variables were first- and third-year physical therapist student GPA, clinical performance scores (first and final clinical experiences), noncognitive student variables, and comprehensive examination scores.

Data Sources

A systematic search was performed using the databases PubMed and EBSCO (1966–2018).

Study Selection

Studies included in the review met the following criteria: the physical therapist education program offered an entry-level master’s or doctorate degree, pertinent data were available for each independent variable, the relationship between the independent variable and the NPTE was investigated, the NPTE was a continuous variable, the program was a US entry-level therapist education program, and the study was peer reviewed.

Data Extraction

Two independent reviewers completed data extraction and quality appraisal using the McMaster Appraisal Tool.

Data Synthesis

Random-effects meta-analyses using the Pearson product-moment correlation coefficient as the measure of effect size was used.

Limitations

Limitations of the review included a lack of homogeneity, high NPTE pass rates, modifications to the McMaster Appraisal Tool, small sample sizes, and publication bias.

Conclusions

No one physical therapist applicant variable should be used as an independent predictor of first attempt NPTE performance. For physical therapist students, first- and third-year physical therapist student GPA had a strong relationship with first attempt NPTE performance; clinical performance had a weak and nonsignificant relationship with first attempt NPTE performance.
A survey on a rural in-hospital population diagnosed with Atrial Fibrillation in west Shewa region, Ethiopia
Authors: Bregani Enrico Rino , Valcarenghi Caterina , Conti Matilde
Published: October 2019

Background

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. It has been extensively studied in Western countries but less is known about developing countries.

Methods

We collected data on a rural population afferent to Wolisso hospital in Ethiopia, analysing epidemiology, clinical and cardiac ultrasound profile.

We enrolled 54 patients with first diagnosis of AF who undertook cardiac ultrasound and a questionnaire about personal and clinical profile.

Results

Enrolled patients were younger than reported in the African urban population (mean age 51 years) and females were symptomatic at a younger age than males (61.8% of females were <50 years old versus 30% of males) and had complicated disease (100% of females had CHF). Rheumatic heart disease (RHD) was found in 38.9% of patients, especially in females (41.1%) and young patients, whereas hypertension (HTN) and degenerative valvular disease were predisposing to AF in old patients.

Conclusion

Low socio-economic level may explain findings we observed, particularly male to female ratio, more relevant than in urban subsets. RHD and HTN are many etiological factors of AF in our small population, so low-cost strategies to prevent their complications are surely cost-effective in rural catchment area of Wolisso hospital.
Viral antigens elicit augmented immune responses in primary Sjögren’s syndrome
Authors: Björk Albin , Thorlacius Gudny Ella , Mofors Johannes , Richardsdotter Andersson Elina , Ivanchenko Margarita , Tingström Joanna , James Tojo , Brokstad Karl A , Cox Rebecca J , Jonsson Roland , Kvarnström Marika , Wahren-Herlenius Marie
Published: October 2019

Objectives

Infections have been suggested in the pathogenesis of primary SS (pSS). Systematic studies of immune responses to microbial antigens in vivo may be performed during vaccination. In the present study, we therefore longitudinally followed patients with pSS and controls during split-virion influenza vaccination to identify pSS-specific cellular, transcriptomic and serological responses.

Methods

Patients without treatment (pSSUntr, n = 17), on hydroxychloroquine-treatment (pSSHCQ, n = 8), and healthy controls (n = 16) were included. Antibody titres were determined by ELISA. Plasma proteins were measured by proximity extension assay. Monocyte gene expression was assessed by Nanostring. Routine laboratory tests were performed and clinical disease symptoms were registered by questionnaires.

Results

pSSUntr developed higher vaccine-specific IgG titres compared with controls. Notably, anti-Ro52 autoantibody titres increased in pSSUntr but remained unchanged in pSSHCQ. No changes in disease symptoms including EULAR Sjögren's Syndrome Patient Reported Index score were registered. Twenty-four hours after vaccination, the leucocyte count in pSSUntr decreased, with a concomitant increase of CCL7 in plasma. Transcriptomic analysis in monocytes revealed differential vaccination-related expression of the NEMO/IKBKG gene, and its higher induced expression in pSSUntr associated with higher serological vaccine responses. Moreover, titres of vaccine-specific antibodies were associated with higher vaccination-induced NF-κB signalling and higher steady-state IFN signatures in monocytes, and with the levels of several plasma proteins with soluble PD-1 displaying the strongest association.

Conclusion

We observed augmented innate and adaptive immune responses in pSS following viral antigen exposure suggesting an underlying hyper-responsiveness to immune challenges, supporting a role for infections driving the immunopathology and acting as environmental risk factor for pSS.
Pathways to the Glass Cliff: A Risk Tax for Women and Minority Leaders?
Authors: Glass Christy , Cook Alison
Published: October 2019

Do women and racial/ethnic minority leaders pay a risk tax on their way to the top? Theories of the glass cliff have focused on the penalties imposed upon women and minority leaders due to bias and discrimination at the time of appointment to top leadership positions. Much less attention has focused on the strategic agency these leaders exercise in response to bias across the career. This paper advances theory and research on the glass cliff by analyzing the choices, decisions, and priorities of white women and people of color that, across the career, result in their appointment to glass cliff positions. Our analysis relies on in-depth, semi-structured interviews with 33 senior leaders across a range of industries. Our findings suggest that rather than isolated instances of high-risk promotions, glass cliff appointments represent the culmination of a long-term career strategy centered on risk and risk-taking. We find evidence that these leaders pay a significant risk tax in order to achieve upward mobility in their organizations.