bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of RNA Polymerase I Transcription Activates Targeted DNA Damage Response and Enhances the Efficacy of PARP Inhibitors in High-Grade Serous Ovarian Cancer
Authors: Sanij Elaine , Hannan Katherine M. , Yan Shunfei , Xuan Jiachen , Ahern Jessica E. , Chan Keefe T. , Son Jinbae , Kondrashova Olga , Lieschke Elizabeth , Wakefield Matthew J. , Trigos Anna S. , Frank Daniel , Ellis Sarah , Cullinane Carleen , Kang Jian , Poortinga Gretchen , Nag Purba , Khanna Kum Kum , Mileshkin Linda , McArthur Grant A. , Soong John , Berns Els M.J.J. , Hannan Ross D , Scott Clare L. , Sheppard Karen E , Pearson Richard B
Published: April 2019

High-grade serous ovarian cancer (HGSOC) accounts for the majority of ovarian cancer and has a dismal prognosis. PARP inhibitors (PARPi) have revolutionized disease management of patients with homologous recombination (HR) DNA repair-deficient HGSOC. However, acquired resistance to PARPi by complex mechanisms including HR restoration and stabilisation of replication forks is a major challenge in the clinic. Here, we demonstrate CX-5461, an inhibitor of RNA polymerase I transcription of ribosomal RNA genes (rDNA), induces replication stress at rDNA leading to activation of DNA damage response and DNA damage involving MRE11-dependent degradation of replication forks. CX-5461 cooperates with PARPi in exacerbating DNA damage and enhances synthetic lethal interactions of PARPi with HR deficiency in HGSOC-patient-derived xenograft (PDX)in vivo. We demonstrate CX-5461 has a different sensitivity spectrum to PARPi and destabilises replication forks irrespective of HR pathway status, overcoming two well-known mechanisms of resistance to PARPi. Importantly, CX-5461 exhibits single agent efficacy in PARPi-resistant HGSOC-PDX. Further, we identify CX-5461-sensitivity gene expression signatures in primary and relapsed HGSOC. Therefore, CX-5461 is a promising therapy alone and in combination therapy with PARPi in HR-deficient HGSOC. CX-5461 is also an exciting treatment option for patients with relapsed HGSOC tumors that have poor clinical outcome.
Female mice are resilient to age-related decline of substantia nigra dopamine neuron firing parameters
Authors: Howell Rebecca D. , Dominguez-Lopez Sergio , Ocañas Sarah , Freeman Willard M. , Beckstead Michael J.
Published: April 2019

The degeneration of substantia nigra (SN) dopamine neurons is a central feature in the pathology associated with Parkinson’s disease, which is characterized by progressive loss of motor and cognitive functions. The largest risk factors for Parkinson’s disease are age and sex; most cases occur after age 60 and males have nearly twice the incidence as females. While much research in Parkinson’s has focused on the mechanisms underlying dopamine neuron degeneration, very little work has considered the influence of these two risk factors to disease risk and presentation. In this work, we performed whole cell patch clamp recordings in brain slices to study the alterations in intrinsic firing properties of single dopamine neurons in C57BL/6 mice across ages and between sexes. We observed a progressive decline in dopamine neuron firing activity in males by 18 months of age, while dopamine neurons from females remained largely unaffected. A semiquantitative analysis of midbrain dopamine neuron populations revealed a slight decrease only in substantia nigra dopamine neurons in males, while females did not change. This was also accompanied by increases in the expression of genes that have been linked to Parkinson’s including PTEN-induced kinase 1 (PINK1) in both males and females, and the ubiquitin ligase parkin, primarily in the substantia nigra of males. These impairments in dopamine neuron function in males may represent a vulnerability to further insults that could predispose these cells to neurodegenerative diseases such as in Parkinson’s.
Systematic determination of in vitro phenotypic resistance to HIV-1 integrase strand transfer inhibitors from clinical samples
Authors: Shahid Aniqa , Zhang Wendy W. , Montoya Vincent , Cheung Peter K. , Oliveira Natalia , Sidhu Manraj S. , Woods Conan K. , Robbins Marjorie A. , Brumme Chanson J. , Harrigan P. Richard
Published: April 2019

Phenotypic resistance data is relatively sparse for the newest HIV-1 integrase strand transfer inhibitors (INSTIs), dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB). In this study, we report the phenotypic susceptibility of a large panel of oligo-clonal patient-derived HIV-1 integrase viruses. Representative clinical samples (N=141) were selected from a large database (N=17,197) of clinically-derived HIV integrase sequences, based on the presence of permutations of substitutions at 27 pre-defined positions in integrase (N=288). HIV-1 RNA was extracted from patient samples and diluted to approximately 500 HIV RNA copies/mL. Using an “oligo-clonal” amplification approach to achieve single-copy amplification, these dilutions were subjected to 12 parallel RT-PCR reactions to amplify integrase. Confirmed clonal amplicons were co-transfected with linearized pNL4.3∆int into CEM-GXR cells. In total, 162 HIV-1 viruses that carried no mixtures and had a unique sequence were harvested, and phenotyped in MT4-LTR-EGFP cells subsequently. Variants with the highest fold change (FC) had G140S and Q148R/H and resistant to all five drugs; R263K was the only single variant conferring >3-FC to DTG, BIC and CAB. There was extensive cross-resistance between DTG, BIC, and CAB and phenotypic resistance values for all the three INSTIs were almost collinear. The greatest exceptions were variants with N155H/G163E or L74I/T97M/F121C/V151I/E157Q/G163K, where both had >70-FC for CAB, while <3-FC for DTG and BIC. While site-directed mutagenesis is invaluable; the systematic selection of representative mutational patterns observedin vivoprovides an efficient way to identify clinically relevant drug resistance.
Investigating Coronary Artery Disease methylome through targeted bisulfite sequencing
Authors: Ghose Subhoshree , Ghosh Sourav , Tanwar Vinay Singh , Tolani Priya , Sharma Anju , Bhardwaj Nitin , Shamsudheen KV , Verma Ankit , Jayarajan Rijith , Sivasubbu Sridhar , Scaria Vinod , Seth Sandeep , Sengupta Shantanu
Published: April 2019

Background

Gene environment interactions leading to epigenetic alterations play pivotal role in the pathogenesis of Coronary Artery Disease (CAD). Altered DNA methylation is one such epigenetic factor that could lead to altered disease etiology. In this study, we comprehensively identified methylation sites in several genes that have been previously associated with young CAD patients.

Methods

The study population consisted of 42 healthy controls and 33 young CAD patients (age group < 50 years). We performed targeted bisulfite sequencing of promoter as well as genic regions of several genes in various pathways like cholesterol synthesis and metabolism, endothelial dysfunction, apoptosis, which are implicated in the development of CAD.

Results

We observed that the genes likeGALNT2, HMGCRwere hypermethylated in the promoter whereasLDLRgene promoter was hypomethylated indicating that intracellular LDL uptake was higher in CAD patients. AlthoughAPOA1did not show significant change in methylation butAPOC3andAPOA5showed variation in methylation in promoter and exonic regions. Glucokinase (GCK) and endothelial nitric oxide synthase 3(NOS3)were hyper methylated in the promoter. Genes involved in apoptosis(BAX/BCL2/AKT2)and inflammation (PHACTR1/LCK) also showed differential methylation between controls and CAD patients.

Conclusions

This study is unique because it highlights important gene methylation alterations which might predict the risk of young CAD in Indian population. Large scale studies in different populations would be important for validating our findings and understanding the epigenetic events associated with CAD.
Critical length in long read resequencing
Authors: Wouter De Coster , Mojca Strazisar , Peter De Rijk
Published: April 2019

Long read sequencing has a substantial advantage for structural variant discovery and phasing of variants compared to short-read technologies, but the required and optimal read length has not been assessed. In this work, we used simulated long reads and evaluated structural variant discovery and variant phasing using current best practice bioinformatics methods. We determined that optimal discovery of structural variants from human genomes can be obtained with reads of minimally 15 kbp. Haplotyping genes entirely only reaches its optimum from reads of 100 kbp. These findings are important for the design of future long read sequencing projects.
Novel feeding and mating behaviors of a population of nautiluses, Nautilus belauensis, in Palau
Authors: Barord Gregory J. , Swanson Rebecca L. , Ward Peter D.
Published: April 2019

The nautiloid lineage extends back nearly 500 million years but today, is represented by only two living genera, Nautilus and Allonautilus. Behavioral observations of these living nautiluses have improved our understanding of how nautiloids, and ammonoids, behaved and interacted in their environment. These behaviors may also help to inform conservation practices. Here, we describe feeding and mating behaviors in wild nautiluses not reported from any other population. In Palau, Nautilus belauensis was observed actively preying on a large, living crab (Chaceon sp.) and performing courtship-like behaviors prior to mating. These behaviors occurred across multiple nights and from different nautiluses, suggesting that the behaviors are characteristic of at least a subset of the population, if not the entire population. Perhaps the behaviors exhibited by the Palauan nautiluses are an outlier and simply a localized characteristic of a far-removed population. Or, perhaps these apparent abnormal behaviors of Palauan nautiluses are what all nautiluses across the Indo-Pacific should be exhibiting. If the latter explanation is correct, we can start to address the potential causes of the behavioral differences, such as population size, habitat type, and prey availability. In either case, this apparent behavioral plasticity may have also been a reason that the nautiloid lineage has been able to survive throughout millions of years of environmental changes. Today, these behavioral observations could prove to be a valuable conservation tool to protect species and environments, especially in the deep-sea ecosystem the nautiluses inhabit.
Structural and spectroscopic investigations on the quenching free luminescence of europium oxalate nanocrystals
Authors: Alexander Dinu , Thomas Kukku , Joy Monu , Biju P. R. , Unnikrishnan N. V. , Joseph Cyriac
Published: April 2019

The structural features leading to the intense quenching free luminescence exhibited by europium oxalate nanocrystals, poly[[hexaaquatri-μ2-oxalato-dieuropium] 4.34-hydrate], {[Eu2(C2O4)3(H2O)6]·4.34H2O}
n
, is the focal point of this report. Europium oxalate nanocrystals were synthesized by a simple microwave-assisted co-precipitation method. Powder X-ray diffraction analysis revealed the monoclinic structure of the nanocrystals and the phase purity. The morphology and particle size were examined by transmission electron microscopy (TEM) analysis. Luminescence measurements on a series of samples of La2–x
Eu
x
(C2O4)3·10H2O, with x varying in the range 0.1 to 2, established the quenching free nature exhibited by the europium oxalate nanocrystals. A single-crystal structure analysis was carried out and the quenching free luminescence is explained on the basis of the crystal structure. A detailed photoluminescence characterization was carried out using excitation and emission studies, decay analysis, and CIE coordinate and colour purity evaluation. The various spectroscopic parameters were evaluated by Judd–Ofelt theoretical analysis and the results are discussed on the basis of the crystal structure analysis.
Completing the picture of tolazamide polymorphism under extreme conditions: a low-temperature study
Authors: Fedorov Alexey Yu. , Rychkov Denis A. , Losev Evgeniy A. , Drebushchak Tatiana N. , Boldyreva Elena V.
Published: April 2019

We present the results of an experimental and computational study of structural changes in two polymorphs of tolazamide {systematic name: 1-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide}, C14H21N3O3S, on cooling to 100 K and reverse heating. No phase transitions occurred in this temperature range. The anisotropy of the thermal expansion was different for the two polymorphs and differed from that reported previously for the hydrostatic compression. The changes in different intermolecular contacts responsible for the strain anisotropy were analysed. Relative shortening of the contacts was related directly to their initial length and reversely to the steric density around them. Increasing steric density is likely to be the driving force for the conformational ordering of the azepane ring under compression.
Crystal structure of the leucine-rich repeat ectodomain of the plant immune receptor kinase SOBIR1
Authors: Hohmann Ulrich , Hothorn Michael
Published: April 2019

Plant-unique membrane receptor kinases with leucine-rich repeat (LRR) extracellular domains are key regulators of development and immune responses. Here, the 1.55 Å resolution crystal structure of the immune receptor kinase SOBIR1 fromArabidopsisis presented. The ectodomain structure reveals the presence of five LRRs sandwiched between noncanonical capping domains. The disulfide-bond-stabilized N-terminal cap harbours an unusual β-hairpin structure. The C-terminal cap features a highly positively charged linear motif which was found to be largely disordered in this structure. Size-exclusion chromatography and right-angle light-scattering experiments suggest that SOBIR1 is a monomer in solution. The protruding β-hairpin, a set of highly conserved basic residues at the inner surface of the SOBIR LRR domain and the presence of a genetic missense allele in LRR2 together suggest that the SOBIR1 ectodomain may mediate protein–protein interaction in plant immune signalling.
Dot sensitivity analysis of ferromagnetic materials for topology optimization in an axi-symmetric magnetostatic system
Authors: Hong SeungGeon , Lee Kang Hyouk , Park Il Han
Published: April 2019

Purpose

The purpose of this paper is to propose dot sensitivity analysis of ferromagnetic materials for topology optimization in an axi-symmetric magnetostatic system.

Design/methodology/approach

The dot sensitivity formula for the axi-symmetric system is derived as a closed form using the continuum shape sensitivity formula. The dot sensitivity method is combined with the level set method to perform topology optimization.

Findings

Derived dot sensitivity analysis can generate a ferromagnetic ring torus in a vacant region. Thus, an initial design is not needed for the design material. Two design problems are tested to demonstrate the usefulness of dot sensitivity.

Originality/value

By simultaneously using the shape sensitivity and dot sensitivity, in axi-symmetric magnetic system, the design space is expanded and it includes the interface and the inside of the vacant region. This property can reduce the possibility of local optimum convergence.
Effects of authentic leadership on work–family balance in China
Authors: Lyu Yijing , Wang Minmin , Le Jiaqi , Kwan Ho Kwong
Published: April 2019

Purpose

The purpose of this paper is to examine the effects of authentic leadership on the work–family balance (WFB) of followers by focusing on the mediating roles of leader–member exchange (LMX) and work-to-family enrichment (WFE) and the moderating role of traditionality in China.

Design/methodology/approach

Data were collected using field survey research design. Participants included 206 employees in a pharmaceutical company in China.

Findings

The results indicate that LMX and WFE sequentially mediated the positive relationship between authentic leadership and WFB. In addition, traditionality strengthened the relationship between authentic leadership and LMX.

Research limitations/implications

This study contributes to the integration of authentic leadership literature and the WFB model. This research also indicates that authentic leadership is a source of enhancing employees’ WFB. However, data are correlational and cross-sectional, which limits the ability to draw causal relationships.

Practical implications

The findings reveal that authentic leadership is effective in inducing followers’ WFB. The value of traditionality can strengthen the effect of authentic leadership.

Originality/value

This study addresses unexplored theoretical predictions and provides new directions for authentic leadership and work–family research.
Audit committee effectiveness and family firms: impact on performance
Authors: Al-Okaily Jihad , Naueihed Salma
Published: April 2019

Purpose

The purpose of this paper is to empirically examine the relationship between audit committee characteristics and firm performance, and whether family ownership and involvement moderate the latter relationship.

Design/methodology/approach

Following Anderson and Reeb (2003), this paper estimates a two-way fixed effects model. A sub-sample analysis is used by first examining the impact of audit committee effectiveness on firm performance only in non-family firms and then only in family firms. A fully interacted model was also analyzed in the robustness tests.

Findings

This paper finds that the audit committee characteristics of size, expertise and meeting frequency are positively and significantly related to non-family firm performance, while insignificantly related to family firm performance.

Research limitations/implications

The evidence reported in this paper may be of use for regulators and policy makers pondering corporate governance reforms, as well as for investors, managers and minority shareholders concerned with firm performance and valuation.

Originality/value

To the best of the authors’ knowledge, this is the first study of its kind to examine the moderating effect of family control and involvement on the relationship between firm performance and audit committee effectiveness in terms of size, expertise and meeting frequency.
A randomised controlled trial of amnioexchange for fetal gastroschisis
Authors: Luton D , Mitanchez D , Winer N , Muller F , Gallot D , Perrotin F , Jouannic J‐M , Bretelle F , de Lagausie P , Ville Y , Guibourdenche J , Oury J‐F , Alberti C , Benachi A
Published: April 2019

Objective

Morbidity in fetuses affected by gastroschisis is mainly the result of bowel ischaemic and inflammatory processes. Experimental studies on animal models show that clearing amniotic fluid from the digestive secretions by amnioexchange procedures reduces the inflammatory process. We evaluated the benefit of the amnioexchange procedure for fetal gastroschisis in humans.

Design

Prospective, interventional, randomised study.

Setting

Eight referral centres for fetal medicine.

Population

Pregnant women carrying a fetus with gastroschisis.

Methods

We compared, in utero, amnioexchange with a sham procedure. The protocol included, in both arms, steroid injections at 30 weeks of gestation and the use of postnatal minimal enteral feeding.

Main outcome measures

The primary outcome was a composite variable based on the duration of ventilation and parenteral nutrition. Secondary outcomes were the effectiveness and safety of the amnioexchange procedure, including the rate of perinatal death, time to full enteral feeding, primary closure, and late feeding disorders.

Results

Sixty‐four patients were randomised. There was no difference in the composite criteria between the amnioexchange and control groups. Based on an intention‐to‐treat analysis, there were no significant between‐group differences in pregnancy outcome or complications. When studying the relationship between digestive compounds and amniotic fluid inflammatory markers, a clear correlation was found between bile acid and both ferritin and interleukin 1β (IL1β).

Conclusions

In humans, amnioexchange, as described in our protocol, is not an option for fetal care; however, we provide supplementary proof of the involvement of inflammation in the pathogenicity of gastroschisis and suggest that future research should aim at reducing inflammation. ClinicalTrials.gov: NCT00127946.

Tweetable abstract

A prospective, interventional, randomised study shows no benefit of amnioexchange for fetal gastroschisis in humans.
Cytological diagnosis of vitreoretinal lymphomas: A case series
Authors: Quintyn Jean‐Claude , Olle Priscille , Courtade‐Saidi Monique , Laurent Camille , Obéric Lucie , Quintyn‐Ranty Marie‐Laure
Published: April 2019

Objective

To assess the cytological diagnosis and follow‐up of patients suffering from vitreoretinal lymphoma (VRL) diagnosed in our institution.

Methods and Results

From January 2010 to June 2017, we collected 15 patients with VRL. Twelve patients had diffuse large B‐cell lymphoma (DLBCL); of these, 11 had primary central nervous system (CNS) DLBCL, one had ocular localisation of follicular lymphoma, one had extranodal NK/T‐cell nasal type lymphoma and one had chronic lymphocytic leukaemia. The results of the cytological examination (cell morphology and immunocytochemistry) of the vitreous fluid were available for 9/15 VRL. The interleukin‐10/‐6 ratio was >1 in eight of 12 DLBCL. Molecular testing was useful in 6/15 cases (clonality evaluation or MYD88 L265P mutation testing). Eight out of 11 primary CNS DLBCL patients had CNS involvement, with 22‐month progression‐free survival. In our series, only two out of 11 CNS DLBCL patients died of disease after 2 and 5 years, respectively.

Conclusions

The short delay to assert the diagnosis of VRL could explain the quite good prognosis in our series, which highlights the need to consider a diagnosis of DLBCL as first step. The cytological features, as a reliable way to identify VRL, must always guide the choice of techniques for further investigations given the small amount of vitreous fluid available for analysis.
Varieties of Limited Access Orders: The nexus between politics and economics in hybrid regimes
Authors: Ademmer Esther , Langbein Julia , Börzel Tanja A.
Published: April 2019

This article advances our understanding of differences in hybrid stability by going beyond existing regime typologies that separate the study of political institutions from the study of economic institutions. It combines the work of Douglass North, John Wallis, and Barry Weingast (NWW) on varieties of social orders with the literature on political and economic regime typologies and dynamics to understand hybrid regimes as Limited Access Orders (LAOs) that differ in the way dominant elites limit access to political and economic resources. Based on a measurement of political and economic access applied to seven post‐Soviet states, the article identifies four types of LAOs. Challenging NWW's claim, it shows that hybrid regimes can combine different degrees of political and economic access to sustain stability. Our typology allows to form theoretical expectations about the kinds of political and/or economic changes that will move different types of LAOs toward more openness or closure.
Sleep and daytime sleepiness in adolescents with and without ADHD: differences across ratings, daily diary, and actigraphy
Authors: Becker Stephen P. , Langberg Joshua M. , Eadeh Hana‐May , Isaacson Paul A. , Bourchtein Elizaveta
Published: April 2019

Background

Children with attention‐deficit/hyperactivity disorder (ADHD) experience greater sleep problems than their peers. Although adolescence is generally a developmental period characterized by insufficient sleep, few studies have used a multi‐informant, multi‐method design, to examine whether sleep differs in adolescents with and without ADHD.

Methods

Targeted recruitment was used to enroll an approximately equal number of eighth‐grade adolescents (mean age = 13 years) with (n = 162) and without ADHD (n = 140). Adolescents and parents completed global ratings of sleep problems; adolescents, parents, and teachers completed ratings of daytime sleepiness. Adolescents wore actigraphs and completed a daily sleep diary for approximately 2 weeks.

Results

Adolescents with ADHD were more likely than adolescents without ADHD to obtain insufficient sleep on school days (per diary) and weekends (per diary and actigraphy). Adolescents with ADHD were also more likely to report falling asleep in class and to have stayed up all night at least twice in the previous 2 weeks (14% and 5% reported all‐nighters for ADHD and comparison, respectively). In regression analyses controlling for a number of variables known to impact sleep (e.g. pubertal development, sex, medication use, having an externalizing, anxiety, or depression diagnosis), ADHD remained associated with shorter diary and actigraphy school night sleep duration, adolescent‐ and parent‐reported daytime sleepiness, and parent‐reported difficulties initiating and maintaining sleep and total sleep disturbance. Controlling for other variables, the odds of being classified with clinically elevated parent‐reported sleep disturbance were 6.20 times greater for adolescents with ADHD.

Conclusions

Findings provide some of the clearest evidence yet that adolescents with ADHD experience more sleep problems and sleepiness than their peers without ADHD. It may be especially important to assess for sleep problems in adolescents with ADHD and to evaluate whether existing sleep interventions are effective, or can be optimized, for use in adolescents with ADHD who also have sleep problems.
Lethal RNA interference response in the pepper weevil
Authors: Wu Ke , Taylor Caitlin E. , Pinheiro Daniele H. , Skelley Lucile H. , McAuslane Heather J. , Siegfried Blair D.
Published: April 2019

The pepper weevil, Anthonomus eugenii Cano (Coleoptera: Curculionidae) is an important pest of peppers (Capsicum spp.) in the southern United States, Mexico, and Central America. Current management practices rely on chemical control of adults although grower options are limited. A more integrated strategy to manage the pepper weevil infestations may benefit from measures that can control this pest specifically such as RNA interference (RNAi). We cloned and sequenced transcript fragments of two possible essential genes of the pepper weevil, Snf7 and V‐ATPase‐A. We treated pepper weevil females with the double‐stranded RNAs (dsRNAs) of these genes and found that orally delivered dsRNA of either gene was not effective in eliciting strong RNAi response or causing mortality. In contrast, Snf7 and V‐ATPase‐A dsRNAs delivered through injections produced robust gene silencing and led to more than 90% mortality within 12 days. Our results suggest that the pepper weevil possesses the molecular machinery needed for a robust RNAi response and that Snf7 and V‐ATPase‐A genes likely encode essential functions in this insect. Moreover, RNAi‐mediated silencing of essential genes can potentially be used to control this pest if strong RNAi response can be induced by orally delivered dsRNA.
Taxonomic notes on Macromitrium catharinense (Bryopsida, Orthotrichaceae) with its new synonyms
Authors: Li Dan Dan , Guo Shui Liang , Fang Yan Ming
Published: April 2019

Macromitrium catharinense Paris is a poorly known moss of the family Orthotrichaceae reported from Brazil. In the present paper, Macromitrium catharinense is taxonomically re‐evaluated, resulting in the synonymization of M. drewii H. Rob. from Ecuador and M. catharinense var. gracilius (Müll. Hal.) Paris from Brazil. The phenetic relationships between M. catharinense and other closely related species of Macromitrium from Brazil and Ecuador are also discussed.
Optimization of medical waste routing problem: The case of TRB1 region in Turkey
Authors: Mete Suleyman , Serin Faruk
Published: April 2019

A fundamental problem concerning medical waste disposal is the evaluation of the real and potential risks arising from waste with the focus on the risk of infection. Therefore, the optimization of medical waste routing from collection to disposal center can minimize the risk of infection. The routing of medical waste considers significant to determine potential routes and select the route with minimum distance. The management of the medical waste is important decision for environmental sustainability and includes the collection, transportation and disposal of these materials. In this paper, a geographic information system (GIS) solution approach is proposed to determine the best location of disposal center. Proposed approach is applied to medical waste transportation between 167 health institutions (collection centers) and predetermined 5 disposal centers through TRB1 region in Turkey, which consist of Malatya, Elaz??, Bingöl and Tunceli provinces. The results of case study are examined and suggestions for future research are provided.
The description and molecular phylogenetic position of a new conifer-associated mite, Setoptus tsugivagus n. sp. (Eriophyoidea, Phytoptidae, Nalepellinae)

Authors: Chetverikov Philipp , Desnitskaya Eugenia A. , Efimov Peter G. , Bolton Samuel , Cvrkovic Tatjana , Petanovic Radmila , Zukoff Sarah , Klimov Pavel , Amrine James , Klimov Pavel
Published: April 2019

A new vagrant eriophyoid mite species, Setoptus tsugivagus n. sp. Chetverikov (Eriophyoidea, Phytoptidae, Nalepellinae, Nalepellini), is described from the needles of the western hemlock, Tsuga heterophylla (Rafinesque) Sargent (Pinaceae) in Vancouver, Canada. The new species can be distinguished from all other members of Setoptus by a distinct pattern of several short longitudinal ridges on the posterior half of the prodorsal shield. Elements of the anal secretory apparatus (ASA) were observed in adults of S. tsugivagus n. sp., suggesting that the ASA is present in both major phylogenetic lineages of Eriophyoidea (Eriophyidae s. l. and Phytoptidae s. l.). Therefore, this structure could be a synapomorphy for all Eriophyoidea. We briefly discuss the function and morphological variety of the ASA in Eriophyoidea. D2 28S rDNA sequences of four nalepelline species were obtained: Boczekella reticulata Bagnyuk 1987 (GenBank accession number MK124605), Nalepella tsugifoliae Keifer 1953 (MK124606), Setoptus pini Boczek, 1964 (MK124607), and S. tsugivagus n. sp. (MK124608). Molecular phylogenetic analyses of D2 28S rDNA sequences of the mites of the subfamily Nalepellinae confirmed monophyly of the tribe Nalepellini and retrieved Setoptus and Nalepella as polyphyletic. Additionally, our data indicate that 28S rDNA sequence KF782472.1, previously reported to be Trisetacus ehmanni Keifer 1963 by Li et al. (2014), belongs to another species of the genus Trisetacus, possibly T. quadrisetus (Thomas), and the sequence KF782471.1, previously reported to be Trisetacus sp., might belong to T. juniperinus (Nalepa). We also discuss the systematics of nalepellines and their host association with conifers.
Seasonal changes in populations of sheep tick, Ixodes ricinus (L., 1758) (Acari: Ixodinae) in natural biotopes of St. Petersburg and Leningrad province, Russian Federation
Authors: Grigoryeva Luydmila Anatolyevna , Tokarevich N.k. , Freilikhman O.A. , Samoylova E.P. , Lunina G.A.
Published: April 2019

Changes in the seasonal activity and age composition of adults and nymphs in populations of the Ixodes ricinus in northwestern Russia have been studied. Adult ticks and nymphs were collected on flag twice a month from April to October in 2014–2016. They were investigated for biological age (light-optical preparations of the midgut after staining fat with Sudan III). DNA isolated from ticks was analyzed using real-time PCR (fluorescent probe technology) for the presence of Borrelia burgdorferi s.l. pathogens based on amplification of the 16SrRNA and Hbb gene fragments.        The season of activity of the adults shows one peak, the largest numbers show up in July–August (September). The population of adults is composed of two generations. The first generation is active from the beginning of the season until nearly its end, mid-October. Until the end of June, young individuals with large fat reserves predominate in the population. From July to the end of September, the adult population is formed mainly of mature individuals. Older individuals in the population appear from mid-July, and become dominating only in August and, mainly, in September. Ticks of the second generation, as young individuals, were recorded from the end of August until the end of the season of activity. The active nymphs were captured from late April until late October. The season of activity of nymphs begins and ends with a 100% content of young individuals. The spring population (April–May) consists of young nymphs, in June the proportions of young and mature are equalized, in July and August the ratio of mature and old nymphs is balanced, in September old individuals prevail, which were not found in October. The first generation is the nymphs who have hatched from August to October during the previous season, and the second one is the nymphs hatching in August of the current year. The lifespan of adults and nymphs can reach 13–15 months. The proportion of infected ticks in May and June is 24.5% and 25%, with the highest rates of in the young (10–12 months) part of population (70–85% of individuals). In July, the number of mature (12–13 months) individuals increases (up to 75–95%), at the same time the average values of infection fall to 20.8%. In August, the shares of mature (45–55%) and old -13–15 months (45–55%) individuals are approximately balanced. Borrelia contamination is also decreasing (14.3%). In September, the number of mature individuals (29.7%) was about 2 times lower than the old ones (65.3%), and the infection rate decreased to 11.4%.        The population of nymphs and adults is composed of two tick generations in the season of activity. The season of activity of adult ticks is holistic; it is not interrupted during the summer months. Infection of adults with Borrelia decreases simultaneously with the ageing of the population.
Molecular Testing of Serial Blood Specimens from Patients with Early Lyme Disease during Treatment Reveals Changing Coinfection with Mixtures of Borrelia burgdorferi Genotypes
Authors: Mosel Michael R. , Carolan Heather E. , Rebman Alison W. , Castro Steven , Massire Christian , Ecker David J. , Soloski Mark J. , Aucott John N. , Eshoo Mark W.
Published: April 2019

Borrelia burgdorferi
is the etiological agent of Lyme disease. In the current study, we used direct-detection PCR and electrospray ionization mass spectrometry to monitor and genotype
B. burgdorferi
isolates from serially collected whole-blood specimens from patients clinically diagnosed with early Lyme disease before and during 21 days of antibiotic therapy.
Refractory urticaria and the importance of diagnosing Schnitzler’s syndrome
Authors: Nham Tina , Saleh Carol , Chu Derek , Vakaljan Stephanie L , Ohayon Jason A , Siegal Deborah M
Published: April 2019

A 52-year-old man presented with chronic urticaria that was refractory to standard chronic spontaneous urticaria (CSU) treatment. Over time, he developed systemic symptoms including fatigue, weight loss, arthralgia and bone pain. His laboratory investigations also became significant for microcytic anaemia, neutrophilia and elevated C reactive protein, erythrocyte sedimentation rate and IgE levels, in addition to an IgM monoclonal protein. He achieved only partial remission with typical medications for CSU including omalizumab, cyclosporine and cetirizine. After 6 years, his worsening symptoms and abnormal investigations led to a rare diagnosis of Schnitzler’s syndrome and a trial of the interleukin 1 receptor antagonist, anakinra, which caused a rapid and complete resolution of his symptoms.
Two-year observation of posterior corneal elevations after small incision lenticule extraction (SMILE) for myopia higher than −10 dioptres
Authors: Zhou Xueyi , Shang Jianmin , Qin Bing , Zhao Yu , Zhou Xingtao
Published: April 2019

Aim

To investigate the change in posterior corneal elevations (PCEs) of eyes with extremely high myopia 2 years after small incision lenticule extraction (SMILE).

Methods

We evaluated 39 eyes of 39 patients with spherical equivalent higher than −10.00 dioptres (D). Using a Scheimpflug camera (Pentacam), we measured change in PCEs at 1 day, 3 months, 6 months and 2 years after SMILE. Another 34 eyes of 34 patients who underwent femtosecond laser-assisted in situ keratomileusis (FS-LASIK) were examined before, at 1 day and long-term after surgery as the control group. For each eye, elevations at central, thinnest, maximal points and 24 other predetermined points were measured.

Results

No significant forward displacements of PCEs were observed in both surgeries. The maximal but not significant forward displacement occurred around 3–6 months following SMILE, and all returned to original levels 6 months postoperatively except superior area. The peripheral area tended to displace backward, while the central area tended forwardly. In both procedures, elevations along horizontal meridians, inferior and temporal hemispheres were significantly higher than those along vertical meridians, superior and nasal hemispheres, respectively (p<0.05). Elevation on the 4 mm, 6 mm diameters at 1 day and on the 6 mm diameter and temporal hemisphere at long-term follow-up postoperatively were significantly higher in FS-LASIK than SMILE (p<0.05). Change in elevations on the 6 mm diameter circle correlated with residual bed thickness (p=0.047).

Conclusions

SMILE is a safe way to correct for myopia higher than −10 D, with PCEs remaining stable 2 years after surgery.
Quality improvement initiative increases total paracentesis and early paracentesis rates in hospitalised cirrhotics with ascites
Authors: Jesudian Arun , Barraza Luis , Steel Peter , Shen Nicole , Schneider Yecheskel , Bodnar David , Farmer Brenna , Dargar Savira , Del Toro Cristina , Sharma Rahul , Brown, Jr. Robert S , Lee Jennifer Inhae
Published: April 2019

Objective

Early paracentesis (EP) for rapid diagnosis of spontaneous bacterial peritonitis is considered best practice in the care of admitted patients with cirrhosis and ascites, but inpatient paracentesis is frequently not performed or delayed. We developed a quality improvement (QI) initiative aimed at increasing the proportion of admitted patients with cirrhosis who undergo paracentesis and EP.

Design 

Pre–post study of a QI initiative.

Setting 

A tertiary care hospital in a major metropolitan area.

Patients 

Hospitalised patients with cirrhosis and ascites.

Interventions

We targeted care providers in the emergency department (ED) by raising awareness of the importance of EP, developing criteria to identify patients at highest risk of SBP who were prioritised for EP by ED providers and restructuring the ED environment to enable timely paracentesis.

Results

76 patients meeting inclusion criteria were admitted during the postintervention 9-month study period. Of these, 91% (69/76) underwent paracentesis during admission versus 71 % (77/109) preintervention (p=0.001). 81% (56/69) underwent EP within 12 hours of presentation or after a predefined acceptable reason for delay versus 48% (37/77) preintervention (p=0.001). There were no significant differences in in-hospital mortality or length of stay before and after intervention.

Conclusion

A multidisciplinary QI intervention targeting care in the ED successfully increased the proportion of patients with cirrhosis and ascites undergoing diagnostic paracentesis during admission and EP within 12 hours of presentation.
A QDWH-based SVD Software Framework on Distributed-memory Manycore Systems
Authors: Sukkari Dalal , Ltaief Hatem , Esposito Aniello , Keyes David
Published: April 2019

This article presents a high-performance software framework for computing a dense SVD on distributed-memory manycore systems. Originally introduced by Nakatsukasa et al. (2010) and Nakatsukasa and Higham (2013), the SVD solver relies on the polar decomposition using the QR Dynamically Weighted Halley algorithm (QDWH). Although the QDWH-based SVD algorithm performs a significant amount of extra floating-point operations compared to the traditional SVD with the one-stage bidiagonal reduction, the inherent high level of concurrency associated with Level 3 BLAS compute-bound kernels ultimately compensates for the arithmetic complexity overhead. Using the ScaLAPACK two-dimensional block cyclic data distribution with a rectangular processor topology, the resulting QDWH-SVD further reduces excessive communications during the panel factorization, while increasing the degree of parallelism during the update of the trailing submatrix, as opposed to relying on the default square processor grid. After detailing the algorithmic complexity and the memory footprint of the algorithm, we conduct a thorough performance analysis and study the impact of the grid topology on the performance by looking at the communication and computation profiling trade-offs. We report performance results against state-of-the-art existing QDWH software implementations (e.g., Elemental) and their SVD extensions on large-scale distributed-memory manycore systems based on commodity Intel x86 Haswell processors and Knights Landing (KNL) architecture. The QDWH-SVD framework achieves up to 3/8-fold speedups on the Haswell/KNL-based platforms, respectively, against ScaLAPACK
PDGESVD
and turns out to be a competitive alternative for well- and ill-conditioned matrices. We finally come up herein with a performance model based on these empirical results. Our QDWH-based polar decomposition and its SVD extension are freely available at https://github.com/ecrc/qdwh.git and https://github.com/ecrc/ksvd.git, respectively, and have been integrated into the Cray Scientific numerical library LibSci v17.11.1.
Near-Optimal and Practical Algorithms for Graph Scan Statistics with Connectivity Constraints
Authors: Cadena Jose , Chen Feng , Vullikanti Anil
Published: April 2019

One fundamental task in network analysis is detecting “hotspots” or “anomalies” in the network; that is, detecting subgraphs where there is significantly more activity than one would expect given historical data or some baseline process. Scan statistics is one popular approach used for anomalous subgraph detection. This methodology involves maximizing a score function over all connected subgraphs, which is a challenging computational problem. A number of heuristics have been proposed for these problems, but they do not provide any quality guarantees. Here, we propose a framework for designing algorithms for optimizing a large class of scan statistics for networks, subject to connectivity constraints. Our algorithms run in time that scales linearly on the size of the graph and depends on a parameter we call the “effective solution size,” while providing rigorous approximation guarantees. In contrast, most prior methods have super-linear running times in terms of graph size. Extensive empirical evidence demonstrates the effectiveness and efficiency of our proposed algorithms in comparison with state-of-the-art methods. Our approach improves on the performance relative to all prior methods, giving up to over 25% increase in the score. Further, our algorithms scale to networks with up to a million nodes, which is 1--2 orders of magnitude larger than all prior applications.
ML, Visibly Pushdown Class Memory Automata, and Extended Branching Vector Addition Systems with States
Authors: Cotton-Barratt Conrad , Murawski Andrzej S. , Ong C.-H. Luke
Published: April 2019

We prove that the observational equivalence problem for a finitary fragment of the programming langauge ML is recursively equivalent to the reachability problem for
extended branching vector addition systems with states
(EBVASS). This result has two natural and independent parts. We first prove that the observational equivalence problem is equivalent to the emptiness problem for a new class of class memory automata equipped with a visibly pushdown stack, called
Visibly Pushdown Class Memory Automata
(VPCMA). Our proof uses the fully abstract game semantics of the language. We then prove that the VPCMA emptiness problem is equivalent to the reachability problem for EBVASS. The results of this article complete our programme to give an automata classification of the ML types with respect to the observational equivalence problem for closed terms.
ChASE
Authors: Winkelmann Jan , Springer Paul , Napoli Edoardo Di
Published: April 2019

Solving dense Hermitian eigenproblems arranged in a sequence with direct solvers fails to take advantage of those spectral properties that are pertinent to the entire sequence and not just to the single problem. When such features take the form of correlations between the eigenvectors of consecutive problems, as is the case in many real-world applications, the potential benefit of exploiting them can be substantial. We present the Chebyshev Accelerated Subspace iteration Eigensolver (ChASE), a modern algorithm and library based on subspace iteration with polynomial acceleration. Novel to ChASE is the computation of the spectral estimates that enter in the filter and an optimization of the polynomial degree that further reduces the necessary floating-point operations. ChASE is written in C++ using the modern software engineering concepts that favor a simple integration in application codes and a straightforward portability over heterogeneous platforms. When solving sequences of Hermitian eigenproblems for a portion of their extremal spectrum, ChASE greatly benefits from the sequence’s spectral properties and outperforms direct solvers in many scenarios. The library ships with two distinct parallelization schemes, supports execution over distributed GPUs, and is easily extensible to other parallel computing architectures.
Leveraging Label-Specific Discriminant Mapping Features for Multi-Label Learning
Authors: Guo Yumeng , Chung Fulai , Li Guozheng , Wang Jiancong , Gee James C.
Published: April 2019

As an important machine learning task, multi-label learning deals with the problem where each sample instance (feature vector) is associated with multiple labels simultaneously. Most existing approaches focus on manipulating the label space, such as exploiting correlations between labels and reducing label space dimension, with identical feature space in the process of classification. One potential drawback of this traditional strategy is that each label might have its own specific characteristics and using identical features for all label cannot lead to optimized performance. In this article, we propose an effective algorithm named LSDM, i.e.,
leveraging label-specific discriminant mapping features for multi-label learning
, to overcome the drawback. LSDM sets diverse ratio parameter values to conduct cluster analysis on the positive and negative instances of identical label. It reconstructs label-specific feature space which includes distance information and spatial topology information. Our experimental results show that combining these two parts of information in the new feature representation can better exploit the clustering results in the learning process. Due to the problem of diverse combinations for identical label, we employ simplified linear discriminant analysis to efficiently excavate optimal one for each label and perform classification by querying the corresponding results. Comparison with the state-of-the-art algorithms on a total of 20 benchmark datasets clearly manifests the competitiveness of LSDM.