bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinimetric properties and suitability of selected quality indicators for assessing antibiotic use in hospitalized adults: a multicentre point prevalence study in 24 hospitals in Germany
Authors: Först Gesche , Kern Winfried V , Weber Nadine , Querbach Christiane , Kleideiter Johannes , Knoth Holger , Hagel Stefan , Ambrosch Andreas , Löbermann Micha , Schröder Philipp , Borde Johannes , Steib-Bauert Michaela , de With Katja ,   ABS-QI Study Group, Binesch Faranak , Clausing Beate , Devide Anette , Donat Martina , Endler Katja , Feihl Susanne , Freidank Annette , Früchtel-Unterholzner Edeltraud , Gödde Norbert , Gründel Ralf , Grzibiela Wolfgang , Kaiser Réné , Kawecki Piotr , Kohlbrenner Stefan , Lerner Johanna , Lörs Edeltraud , Müller Matthias , Papathanasiou Nikolas , Peltroche Heidrun , Probst Wiltrud , Putzbach Jens , Reimer Marion , Reinwald Ann-Christin , Rusche Ruth , Scheerer Martin , Schulz Claudia , Zessin Enrico
Published: July 2019

Objectives

The capability to measure and monitor the quality of antibiotic prescribing is an important component of antibiotic stewardship (ABS) programmes. Several catalogues of consensus-based structure and process-of-care quality indicators (QIs) have been proposed, but only a few studies have tested and validated ABS QIs in practice tests. This multicentre study determined the clinimetric properties and suitability of a set of 33 process QIs for ABS that had earlier been developed and in part recommended in a German–Austrian hospital ABS practice guideline.

Methods

Two point prevalence surveys were conducted in a convenience sample of 24 acute care hospitals throughout Germany, and data of all screened adult inpatients with prescription of a systemic antibiotic at a given day (n=4310) were included in the study. For each QI, the following clinimetric properties were assessed: applicability, feasibility, performance, case mix stability and interobserver reliability.

Results

Eighteen QIs were considered sufficiently feasible, applicable and reliable, and had adequate room for improvement. The finally selected QIs primarily cover antibiotic therapy of common infections (bloodstream infection, pneumonia and urinary tract infection), while two of the QIs each address surgical prophylaxis and general aspects of antibiotic administration.

Conclusions

Practice tests may be important to test the suitability of consensus process-of-care QIs in the field of hospital ABS. The 18 selected QIs considered suitable enough for hospital ABS in this study should be regarded as priority QIs useful for internal quality control and assurance. More research and additional practice tests may be needed to confirm their suitability for external quality assessment schemes.
Taxonomy of the Sylvilagus brasiliensis complex in Central and South America (Lagomorpha: Leporidae)
Authors: Ruedas Luis A , Silva Sofia Marques , French Johnnie H , Platt Roy Nelson , Salazar-Bravo Jorge , Mora José M , Thompson Cody W
Published: July 2019

A taxonomic framework for South American cottontail rabbits (Lagomorpha: Leporidae: Sylvilagus) was recently published by Diersing and Wilson (2017). Although we agree with some of its taxonomic conclusions (e.g., species status for S. apollinaris and S. fulvescens), we disagree with others. We provide herein evidence supporting S. andinus as a valid species based on morphological characters and novel molecular data. We also provide details of the morphological characters of S. apollinaris and S. fulvescens that support separating these from S. brasiliensis. We adduce data suggestive to the effect that—absent any type material—S. defilippi is at best a nomen dubium. Finally, we provide evidence in support of recognizing additional Neotropical species of Sylvilagus.

Un esquema taxonómico para los conejos sudamericanos (Lagomorpha: Leporidae: Sylvilagus) fue recientemente publicado por Diersing y Wilson (2017). Aunque estamos de acuerdo con algunas de sus conclusiones (por ejemplo: estatus de especie válida para S. apollinaris y S. fulvescens), no estamos de acuerdo con las restantes conclusiones taxonómicas. Aportamos aquí pruebas convincentes sobre la característica naturaleza de los caracteres morfológicos y moleculares de S. andinus, pruebas que esgrimimos en apoyo de la hipótesis que esta última es una especie válida, así confirmando su escisión de S. brasiliensis. Proporcionamos detalles de los caracteres morfológicos de S. apollinaris y S. fulvescens que confirman la decisión taxonómica de asimismo separarlos de S. brasiliensis. Proporcionamos datos en aditamento que indican que a falta de cualquier material tipo para S. defilippi, este nombre es en el mejor de los casos un nomen dubium. Finalmente, ofrecemos datos y evidencia apoyando nuestras decisiones de reconocer un mayor número de especies Neotropicales de Sylvilagus que previamente se conocían.
Possible origin of the slow-diffusion region around Geminga
Authors: Fang Kun , Bi Xiao-Jun , Yin Peng-Fei
Published: July 2019

Geminga pulsar is surrounded by a multiTeV γ-ray halo radiated by the high-energy electrons and positrons accelerated by the central pulsar wind nebula (PWN). The angular profile of the γ-ray emission reported by High-Altitude Water Cherenkov Observatory indicates an anomalously slow diffusion for the cosmic-ray electrons and positrons in the halo region around Geminga. In the paper we study the possible mechanism for the origin of the slow diffusion. At first, we consider the self-generated Alfvén waves due to the streaming instability of the electrons and positrons released by Geminga. However, even considering a very optimistic scenario for the wave growth, we find this mechanism does not work to account for the extremely slow diffusion at the present day, if taking the proper motion of Geminga pulsar into account. The reason is straightforward as the PWN is too weak to generate enough high-energy electrons and positrons to stimulate strong turbulence at the late time. We then propose an assumption that the strong turbulence is generated by the shock wave of the parent supernova remnant (SNR) of Geminga. Geminga may still be inside the SNR, and we find that the SNR can provide enough energy to generate the slow-diffusion circumstance. The TeV haloes around PSR B0656+14, Vela X, and PSR J1826-1334 may also be explained under this assumption.
Basilisk: Bayesian hierarchical inference of the galaxy–halo connection using satellite kinematics – I. Method and validation
Authors: van den Bosch Frank C , Lange Johannes U , Zentner Andrew R
Published: July 2019

We present a Bayesian hierarchical inference formalism (Basilisk) to constrain the galaxy–halo connection using satellite kinematics. Unlike traditional methods, Basilisk does not resort to stacking the kinematics of satellite galaxies in bins of central luminosity, and does not make use of summary statistics, such as satellite velocity dispersion. Rather, Basilisk leaves the data in its raw form and computes the corresponding likelihood. In addition, Basilisk can be applied to flux-limited, rather than volume-limited samples, greatly enhancing the quantity and dynamic range of the data. And finally, Basilisk is the only available method that simultaneously solves for halo mass and orbital anisotropy of the satellite galaxies, while properly accounting for scatter in the galaxy–halo connection. Basilisk uses the conditional luminosity function to model halo occupation statistics, and assumes that satellite galaxies are a relaxed tracer population of the host halo’s potential with kinematics that obey the spherical Jeans equation. We test and validate Basilisk using mocks of varying complexity, and demonstrate that it yields unbiased constraints on the galaxy–halo connection and at a precision that rivals galaxy–galaxy lensing. In particular, Basilisk accurately recovers the full PDF of the relation between halo mass and central galaxy luminosity, and simultaneously constrains the orbital anisotropy of the satellite galaxies. Basilisk ’s inference is not affected by potential velocity bias of the central galaxies, or by slight errors in the inferred, radial profile of satellite galaxies that arise as a consequence of interlopers and sample impurity.
The Kelvin–Helmholtz instability and smoothed particle hydrodynamics
Authors: Tricco Terrence S
Published: July 2019

We perform simulations of the Kelvin–Helmholtz instability using smoothed particle hydrodynamics (SPH). The instability is studied both in the linear and strongly non-linear regimes. The smooth, well-posed initial conditions of Lecoanet et al. (2016) are used, along with an explicit Navier–Stokes viscosity and thermal conductivity to enforce the evolution in the non-linear regime. We demonstrate convergence to the reference solution using SPH. The evolution of the vortex structures and the degree of mixing, as measured by a passive scalar ‘colour’ field, match the reference solution. Tests with an initial density contrast produce the correct qualitative behaviour. The $\mathcal {L}_2$ error of the SPH calculations decreases as the resolution is increased. The primary source of error is numerical dissipation arising from artificial viscosity, and tests with reduced artificial viscosity have reduced $\mathcal {L}_2$ error. A high-order smoothing kernel is needed in order to resolve the initial velocity amplitude of the seeded mode and inhibit excitation of spurious modes. We find that standard SPH with an artificial viscosity has no difficulty in correctly modelling the Kelvin–Helmholtz instability and yields convergent solutions.
Optical follow-up of the tidal disruption event iPTF16fnl: new insights from X-shooter observations
Authors: Onori F , Cannizzaro G , Jonker P G , Fraser M , Kostrzewa-Rutkowska Z , Martin-Carrillo A , Benetti S , Elias-Rosa N , Gromadzki M , Harmanen J , Mattila S , Strizinger M D , Terreran G , Wevers T
Published: July 2019

We present the results from Nordic Optical Telescope and X-shooter follow-up campaigns of the tidal disruption event (TDE) iPTF16fnl, covering the first ∼100 d after the transient discovery. We followed the source photometrically until the TDE emission was no longer detected above the host galaxy light. The bolometric luminosity evolution of the TDE is consistent with an exponential decay with e-folding constant t0 = 17.6 ± 0.2 d. The early-time spectra of the transient are dominated by broad He ii λ4686, H $\beta$, H $\alpha$, and N iii λ4100 emission lines. The latter is known to be produced together with the N iii λ4640 in the Bowen fluorescence mechanism. Due to the medium-resolution X-shooter spectra we have been able to separate the Bowen blend contribution from the broad He ii emission line. The detection of the Bowen fluorescence lines in iPTF16fnl place this transient among the N-rich TDE subset. In the late-time X-shooter spectra, narrow emission lines of [O iii] and [N ii] originating from the host galaxy are detected, suggesting that the host galaxy harbours a weak active galactic nucleus in its core. The properties of all broad emission lines evolve with time. The equivalent widths follow an exponential decay compatible with the bolometric luminosity evolution. The full width at half-maximum of the broad lines decline with time and the line profiles develop a narrow core at later epochs. Overall, the optical emission of iPTF16fnl can be explained by being produced in an optically thick region in which high densities favour the Bowen fluorescence mechanism and where multiple electron scatterings are responsible for the line broadening.
Zoom-in cosmological hydrodynamical simulation of a star-forming barred, spiral galaxy at redshift z = 2
Authors: Vincenzo Fiorenzo , Kobayashi Chiaki , Yuan Tiantian
Published: July 2019

We present gas and stellar kinematics of a high-resolution zoom-in cosmological chemodynamical simulation, which fortuitously captures the formation and evolution of a star-forming barred spiral galaxy, from redshift z ∼ 3 to z ∼ 2 at the peak of the cosmic star formation rate. The galaxy disc grows by accreting gas and substructures from the environment. The spiral pattern becomes fully organized when the gas settles from a thick (with vertical dispersion σv > 50 km s−1) to a thin (σv ∼ 25 km s−1) disc component in less than 1 Gyr. Our simulated disc galaxy also has a central X-shaped bar, the seed of which formed by the assembly of dense gas-rich clumps by z ∼ 3. The star formation activity in the galaxy mainly happens in the bulge and in several clumps along the spiral arms at all redshifts, with the clumps increasing in number and size as the simulation approaches z = 2. We find that stellar populations with decreasing age are concentrated towards lower galactic latitudes, being more supported by rotation, and having also lower velocity dispersion; furthermore, the stellar populations on the thin disc are the youngest and have the highest average metallicities. The pattern of the spiral arms rotates like a solid body with a constant angular velocity as a function of radius, which is much lower than the angular velocity of the stars and gas on the thin disc; moreover, the angular velocity of the spiral arms steadily increases as a function of time, always keeping its radial profile constant. The origin of our spiral arms is also discussed.
L’importance des relations : comment les cliniciens peuvent soutenir des pratiques parentales positives pendant la petite enfance
Authors: Williams Robin C , Biscaro Anne , Clinton Jean
Published: July 2019

Il est essentiel que l’enfant forme des liens d’attachement stables avec au moins un adulte en bonne santé pour développer des capacités d’adaptation optimales. Les professionnels de la santé de première ligne, tels que les pédiatres et les médecins de famille, peuvent y contribuer en soutenant les parents dans leur milieu de pratique. Le clinicien peut profiter de chaque rencontre pour s’informer auprès des parents des relations et des comportements des enfants, des habitudes quotidiennes et du fonctionnement global de la famille. Le présent document de principes, qui porte sur les enfants de 0 à six ans, décrit les principes de base pour soutenir des pratiques parentales positives et recommande des pratiques en cabinet pour promouvoir des relations parents-enfant stables, mobiliser les familles et établir un climat de confiance avec les parents. Les pleurs, le sommeil et les comportements difficiles sont décrits comme des occasions pour le clinicien de donner des conseils préventifs et réceptifs aux besoins des parents.
Associations between family characteristics and influenza vaccination coverage among children
Authors: Ding Xiaofei , Tian Changwei , Wang Hua , Wang Wenming , Luo Xiaoming
Published: July 2019

Background

To assess the associations between family characteristics and influenza vaccination coverage among children.

Methods

Data were used from the National Health Interview Survey 2011–2016.

Results

The number of children ranged from 10 720 to 12 991 per year from 2011 to 2016. After adjustment for the high-risk status of influenza complications, sex, age, region, race and office visits of children, children of adults who received influenza vaccination were 3.83–4.79 times (the lowest and the highest odds ratios from 2011 to 2016) more likely to be immunized for influenza. Health insurance (1.36–1.61) was also associated with vaccination in children. However, the education level of family adults (0.59–0.79) and marital status of being widowed/divorced/separated (0.74–0.79) were negatively associated with vaccination uptake in children. The following characteristics were not major concerns with influenza vaccination in children: class of worker, years on the job, physical activity, drinking, smoking, hepatitis B immunization, number of family members aged ≥65 years and the ratio of family income to the poverty threshold. Overall, results from the pooled analysis (2011–2016) were consistent with the above-mentioned findings.

Conclusions

Promoting parental influenza immunization and access to health insurance may be the most effective tools to promote the coverage of influenza vaccine among children.
Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome
Authors: Modinos Gemma , Allen Paul , Zugman Andre , Dima Danai , Azis Matilda , Samson Carly , Bonoldi Ilaria , Quinn Beverly , Gifford George W G , Smart Sophie E , Antoniades Mathilde , Bossong Matthijs G , Broome Matthew R , Perez Jesus , Howes Oliver D , Stone James M , Grace Anthony A , McGuire Philip
Published: July 2019

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis.
Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity
Authors: de Lima-Junior Jose Carlos , Virginio Vitor W.M. , Moura Filipe A. , Bertolami Adriana , Bertolami Marcelo , Coelho-Filho Otavio R , Zanotti Ilaria , Nadruz Wilson , de Faria Eliana Cotta , de Carvalho Luiz Sergio F. , Sposito Andrei C
Published: July 2019

Objective

Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. Besides, potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range.

Methods

Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. HDL functions were measured in a subgroup (n=101).

Results

Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI. CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely associated with HDL-mediated inhibition of platelet aggregation and CEC, but surprisingly it was directly associated with the antioxidant activity. Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden.

Conclusion

Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.
fMRI as an outcome measure in clinical trials: A systematic review in clinicaltrials.gov
Authors: Sadraee Alaleh , Paulus Martin P. , Ekhtiari Hamed
Published: July 2019

Background

Functional magnetic resonance imaging (fMRI) is quickly becoming a significant outcome measure for clinical trials and as more than one thousand trials with fMRI as an outcome measure were registered in clinicaltrials.gov at the time of writing this article. However, 93% of these registered trials are still not completed with published results and there is no picture available about methodological dimensions of these ongoing trials with fMRI as an outcome measure.

Methods

We collected trials that use fMRI as an outcome measure by searching “fMRI” in the ClinicalTrials.gov registry on October 13 2018 and reviewing each trial’s record entry. Eligible trials’ characteristics were extracted and summarized.

Results

In total, 1386 clinical trials were identified that reported fMRI in their outcome measures with fMRI as the only primary outcome in 33% of them. 82% of fMRI trials were started after 2011. The most frequent intervention was drug (29%). 57% of trials had parallel assignment design and 20% were designed for cross over assignment. For task-based fMRI, cognitive systems (46%) based on RDoC was the most frequent domain of tasks, followed by positive valence systems (19%), systems for social processing (10%) and sensorimotor systems (5%). Less than one-third of trials (28%) registered at least one region of interest for their analysis. Food cue reactivity task, pain perception task, n-back task and monetary incentive delay task were recruited in more than 25 registered trials.

Conclusion

The number of fMRI trials (fMRI as an outcome measure) with both task and rest protocols is growing rapidly. Different RDoC domains are covered by various tasks in fMRI trials. However, our study suggests the need of greater harmony and better standardization for registration of fMRI details on both methods and analysis which would allow for more effective comparison across studies in systematic reviews and also help the validation of results towards having fMRI as a biomarker in the future.
The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier
Authors: Brohawn Stephen G. , Wang Weiwei , Schwarz Jürgen R. , Handler Annie , Campbell Ernest B. , MacKinnon Roderick
Published: July 2019

TRAAK is a membrane tension-activated K+channel that has been associated through behavioral studies to mechanical nociception. We used specific monoclonal antibodies in mice to show that TRAAK is localized exclusively to nodes of Ranvier, the action potential propagating elements of myelinated nerve fibers. Approximately 80 percent of myelinated nerve fibers throughout the central and peripheral nervous system contain TRAAK in an all-nodes or no-nodes per axon fashion. TRAAK is not observed at the axon initial segment where action potentials are first generated. We used polyclonal antibodies, the TRAAK inhibitor RU2 and node clamp amplifiers to demonstrate the presence and functional properties of TRAAK in rat nerve fibers. TRAAK contributes to the ‘leak’ K+current in mammalian nerve fiber conduction by hyperpolarizing the resting membrane potential, thereby increasing Na+channel availability for action potential propagation. Mechanical gating in TRAAK might serve a neuroprotective role by counteracting mechanically-induced ectopic action potentials. Alternatively, TRAAK may open in response to mechanical forces in the nodal membrane associated with depolarization during saltatory conduction and thereby contribute to repolarization of the node for subsequent spikes.
Taxon appearance from extraction and amplification steps demonstrates the value of multiple controls in tick microbiota analysis
Authors: Lejal Emilie , Estrada-Peña Agustín , Marsot Maud , Cosson Jean-François , Rué Olivier , Mariadassou Mahendra , Midoux Cédric , Vayssier-Taussat Muriel , Pollet Thomas
Published: July 2019

Background

The development of high throughput sequencing technologies has substantially improved analysis of bacterial community diversity, composition, and functions. Over the last decade, high throughput sequencing has been used extensively to identify the diversity and composition of tick microbial communities. However, a growing number of studies are warning about the impact of contamination brought along the different steps of the analytical process, from DNA extraction to amplification. In low biomass samples, e.g. individual tick samples, these contaminants may represent a large part of the obtained sequences, and thus generate considerable errors in downstream analyses and in the interpretation of results. Most studies of tick microbiota either do not mention the inclusion of controls during the DNA extraction or amplification steps, or consider the lack of an electrophoresis signal as an absence of contamination. In this context, we aimed to assess the proportion of contaminant sequences resulting from these steps. We analyzed the microbiota of individual Ixodes ricinus ticks by including several categories of controls throughout the analytical process: crushing, DNA extraction, and DNA amplification.

Results

Controls yielded a significant number of sequences (1,126 to 13,198 mean sequences, depending on the control category). Some operational taxonomic units (OTUs) detected in these controls belong to genera reported in previous tick microbiota studies. In this study, these OTUs accounted for 50.9% of the total number of sequences in our samples, and were considered contaminants. Contamination levels (i.e. the percentage of sequences belonging to OTUs identified as contaminants) varied with tick stage and gender: 76.3% of nymphs and 75% of males demonstrated contamination over 50%, while most females (65.7%) had rates lower than 20%. Contamination mainly corresponded to OTUs detected in crushing and DNA extraction controls, highlighting the importance of carefully controlling these steps.

Conclusion

Here, we showed that contaminant OTUs from extraction and amplification steps can represent more than half the total sequence yield in sequencing runs, and lead to unreliable results when characterizing tick microbial communities. We thus strongly advise the routine use of negative controls in tick microbiota studies, and more generally in studies involving low biomass samples.
A polygenic and phenotypic risk prediction for Polycystic Ovary Syndrome evaluated by Phenome-wide association studies
Authors: Joo Yoonjung Yoonie , Actkins Ky’Era , Pacheco Jennifer A. , Basile Anna O. , Carroll Robert , Crosslin David R. , Day Felix , Denny Joshua C. , Velez Edwards Digna R. , Hakonarson Hakon , Harley John B. , Hebbring Scott J , Ho Kevin , Jarvik Gail P. , Jones Michelle , Karderi Tugce , Mentch Frank D. , Meun Cindy , Namjou Bahram , Pendergrass Sarah , Ritchie Marylyn D. , Stanaway Ian B. , Urbanek Margrit , Walunas Theresa L. , Smith Maureen , Chisholm Rex L. ,   International PCOS Consortium, Kho Abel N. , Davis Lea , Hayes M. Geoffrey
Published: July 2019

Purpose

As many as 75% of patients with Polycystic ovary syndrome (PCOS) are estimated to be unidentified in clinical practice. Utilizing polygenic risk prediction, we aim to identify the phenome-wide comorbidity patterns characteristic of PCOS to improve accurate diagnosis and preventive treatment.

Methods and Findings

Leveraging the electronic health records (EHRs) of 124,852 individuals, we developed a PCOS risk prediction algorithm by combining polygenic risk scores (PRS) with PCOS component phenotypes into a polygenic and phenotypic risk score (PPRS). We evaluated its predictive capability across different ancestries and perform a PRS-based phenome-wide association study (PheWAS) to assess the phenomic expression of the heightened risk of PCOS. The integrated polygenic prediction improved the average performance (pseudo-R2) for PCOS detection by 0.228 (61.5-fold), 0.224 (58.8-fold), 0.211 (57.0-fold) over the null model across European, African, and multi-ancestry participants respectively. The subsequent PRS-powered PheWAS identified a high level of shared biology between PCOS and a range of metabolic and endocrine outcomes, especially with obesity and diabetes: ‘morbid obesity’, ‘type 2 diabetes’, ‘hypercholesterolemia’, ‘disorders of lipid metabolism’, ‘hypertension’ and ‘sleep apnea’ reaching phenome-wide significance.

Conclusions

Our study has expanded the methodological utility of PRS in patient stratification and risk prediction, especially in a multifactorial condition like PCOS, across different genetic origins. By utilizing the individual genome-phenome data available from the EHR, our approach also demonstrates that polygenic prediction by PRS can provide valuable opportunities to discover the pleiotropic phenomic network associated with PCOS pathogenesis.
Targeted optimization of regulatory DNA sequences with neural editing architectures
Authors: Gupta Anvita , Kundaje Anshul
Published: July 2019

Targeted optimizing of existing DNA sequences for useful properties, has the potential to enable several synthetic biology applications from modifying DNA to treat genetic disorders to designing regulatory elements to fine tune context-specific gene expression. Current approaches for targeted genome editing are largely based on prior biological knowledge or ad-hoc rules. Few if any machine learning approaches exist for targeted optimization of regulatory DNA sequences.

Here, we propose a novel generative neural network architecture for targeted DNA sequence editing – the EDA architecture – consisting of an encoder, decoder, and analyzer. We showcase the use of EDA to optimize regulatory DNA sequences to bind to the transcription factor SPI1. Compared to other state-of-the-art approaches such as a textual variational autoencoder and rule-based editing, EDA significantly improves predicted binding of SPI1 of genomic sequences with the minimal set of edits. We also use EDA to design regulatory elements with optimized grammars of CREB1 binding sites that can tune reporter expression levels as measured by massively parallel reporter assays (MPRA). We analyze the properties of the binding sites in the edited sequences and find patterns that are consistent with previously reported grammatical rules which tie gene expression to CRE binding site density, spacing and affinity.
Infection ofBorrelia burgdorferisensu lato of small mammals in Yunnan Province, China
Authors: He Zhi-hai , Jiang Bao-gui , Gao Zi-hou , Shao Zong-ti , Zhang Yun , Liu Zheng-xiang , Li Yu-qiong , Pu En-nian , Tang Li , Yao Ming-guo , Jia Na , von Fricken Michael E. , Jiang Jia-fu , Cao Wu-chun , Du Chun-hong
Published: July 2019

Background

Lyme disease is caused byBorrelia burgdorferisensulato (BBSL) which is usually found in wild and domestic mammals worldwide. Human cases ofB. burgdorferiinfections have been identified in China, but little direct surveillance of potential rodent reservoirs has been performed in Yunnan Province, Southwestern China. Yunnan Province is a tropical area with a diverse topographic range and sustains a high biodiversity of small mammals that could potentially play an important role in the transmission of a variety ofB. burgdorferigenospecies.

Methods

3659 small mammals were captured in 159 sample siteslocated 23 countries inYunnan Province and screened for BBSL infection by nested PCR based on 5S-23S rRNA intergenic spacer gene of BBSL.Univariate and multivariate forward stepwise logistic regression analysis was used to access the association between infections and related risk factors.

Results

Infection with BBSL was confirmed in 3.99%(146/3659) of small mammals. Significant differences in prevalence rates of BBSL were observed at varying landscape types and altitudes.Small mammals in forested areas had higher prevalence rates than other landscape types as did small mammals found at altitudes greater than 2500 meters. The 5S-23S rRNA intergenic spacergene revealed that there were 5 genotype of BBSL, includingB. afzelii, B. burgdorferisensustricto, B.japonica, B.gariniiand B.valaisiana, which demonstrate the genetic diversity and regional distribution.

Conclusions

There exists a wide distribution and genetic diversity of endemic BBSL in Southwestern China, warranting further investigations and monitoring of clinical disease in individuals presenting with symptoms of Lyme disease in these areas.

Author summary

Lyme disease is caused byBorrelia burgdorferisensu lato (BBSL) which is usually found in wild and domestic mammals worldwide. Human cases ofBorrelia burgdorferisensu lato infections have been identified in China, but little direct surveillance of potential rodent reservoirs has been performed in Southwestern China. This study documents potential small mammal reservoir hosts collected from a large of sample sites from different landscape types and altitudes, with PCR and sequencing identifying the wide distribution and genetic diversity of endemicBorrelia burgdorferisensu lato in Southwestern China. This was the first report thatB. japonicawas detected inApodemus dracoandNiviventer excelsiorin China. This study adds to body of literature onBorrelia burgdorferisensu lato in China. This work will provide insight regarding small mammals to target for surveillance and we access the association between gender, developmental stage of rodents, environmental landscape and altitude to better prevent human exposure.
Conjugated linoleic acid as a novel insecticide targeting the agricultural pestLeptinotarsa decemlineata
Authors: Clements Justin , Groves Russell L. , Cava JoAnn , Barry Caroline , Chapman Scott , Olson Jake M.
Published: July 2019

The Colorado Potato Beetle,Leptinotarsa decemlineata, is a major agricultural pest of solanaceous crops in the United States. Historically, a multitude of insecticides have been used to control problematic populations. Due to increasing resistance to insecticides, novel compounds and methodologies are warranted for the control of beetle populations. Mixed-isomer conjugated linoleic acid has been studied in-depth for its beneficial properties to mammalian systems. At the same time, studies have demonstrated that conjugated linoleic acid can manipulate fatty acid composition in non-mammalian systems, resulting in embryo mortality. Consequently, experiments were conducted to assess the effects of foliar-applied conjugated linoleic acid on larval growth, embryogenesis, and feeding preference in Colorado potato beetle. Both maternal and deterrent effects of dietary conjugated linoleic acid were assessed. Conjugated linoleic acid demonstrated desirable insecticidal properties, including increased larval mortality, slowed larval development, antifeedant effects, and decreased egg viability after maternal ingestion.
Pyruvate Kinase M Links Glucose Availability to Protein Synthesis
Authors: Kejiou Nevraj S. , Ilan Lena , Aigner Stefan , Luo Enching , Rabano Ines , Rajakulendran Nishani , Najafabadi Hamed S. , Angers Stephane , Yeo Gene W. , Palazzo Alexander F.
Published: July 2019

How human cells coordinate various metabolic processes, such as glycolysis and protein translation, remains unclear. One key insight is that various metabolic enzymes have been found to associate with mRNAs, however whether these enzymes regulate mRNA biology in response to changes in cellular metabolic state remains unknown. Here we report that the glycolytic enzyme, pyruvate kinase M (PKM), inhibits the translation of 7% of the transcriptome in response to elevated levels of glucose and pyruvate. Our data suggest that in the presence of glucose and pyruvate, PKM associates with ribosomes that are synthesizing stretches of polyacidic nascent polypeptides and stalls the elongation step of translation. PKM-regulated mRNAs encode proteins required for the cell cycle and may explain previous results linking PKM to cell cycle regulation. Our study uncovers an unappreciated link between glycolysis and the ribosome that likely coordinates the intake of glycolytic metabolites with the regulation of protein synthesis and the cell cycle.
Machine Learning for Prioritization of Thermostabilizing Mutations for G-protein Coupled Receptors
Authors: Muk S. , Ghosh S. , Achuthan S. , Chen X. , Yao X. , Sandhu M. , Griffor M. C. , Fennell K. F. , Che Y. , Shanmugasundaram V. , Qiu X. , Tate C. G. , Vaidehi N.
Published: July 2019

Although the three-dimensional structures of G-protein-coupled receptors (GPCRs), the largest superfamily of drug targets, have enabled structure-based drug design, there are no structures available for 87% of GPCRs. This is due to the stiff challenge in purifying the inherently flexible GPCRs. Identifying thermostabilized mutant GPCRs via systematic alanine scanning mutations has been a successful strategy in stabilizing GPCRs, but it remains a daunting task for each GPCR. We developed a computational method that combines sequence, structure and dynamics based molecular properties of GPCRs that recapitulate GPCR stability, with four different machine learning methods to predict thermostable mutations ahead of experiments. This method has been trained on thermostability data for 1231 mutants, the largest publicly available dataset. A blind prediction for thermostable mutations of the Complement factor C5a Receptor retrieved 36% of the thermostable mutants in the top 50 prioritized mutants compared to 3% in the first 50 attempts using systematic alanine scanning.

Statement Of Signifigance

G-protein-coupled receptors (GPCRs), the largest superfamily of membrane proteins play a vital role in cellular physiology and are targets to blockbuster drugs. Hence it is imperative to solve the three dimensional structures of GPCRs in various conformational states with different types of ligands bound. To reduce the experimental burden in identifying thermostable GPCR mutants, we report a computational framework using machine learning algorithms trained on thermostability data for 1231 mutants and features calculated from analysis of GPCR sequences, structure and dynamics to predict thermostable mutations ahead of experiments. This work represents a significant advancement in the development, validation and testing of a computational framework that can be extended to other class A GPCRs and helical membrane proteins.
A survey on data-driven process monitoring and diagnostic methods for variation reduction in multi-station assembly systems
Authors: Liu Yinhua , Sun Rui , Jin Sun
Published: July 2019

Purpose

Driven by the development in sensing techniques and information and communications technology, and their applications in the manufacturing system, data-driven quality control methods play an essential role in the quality improvement of assembly products. This paper aims to review the development of data-driven modeling methods for process monitoring and fault diagnosis in multi-station assembly systems. Furthermore, the authors discuss the applications of the methods proposed and present suggestions for future studies in data mining for quality control in product assembly.

Design/methodology/approach

This paper provides an outline of data-driven process monitoring and fault diagnosis methods for reduction in variation. The development of statistical process monitoring techniques and diagnosis methods, such as pattern matching, estimation-based analysis and artificial intelligence-based diagnostics, is introduced.

Findings

A classification structure for data-driven process control techniques and the limitations of their applications in multi-station assembly processes are discussed. From the perspective of the engineering requirements of real, dynamic, nonlinear and uncertain assembly systems, future trends in sensing system location, data mining and data fusion techniques for variation reduction are suggested.

Originality/value

This paper reveals the development of process monitoring and fault diagnosis techniques, and their applications in variation reduction in multi-station assembly.
Study on the effect of surface tannic acid/silane conversion film on properties of epoxy resin coatings
Authors: Xing Tianji , Ying Lixia , Wu Chunxi , Fu Zhen , Wang Guixiang
Published: July 2019

Purpose

The purpose of this paper is to improve binding force between the coating and the steel substrate by using chemical modification on the steel surface; at the same time, it can also increase the corrosion resistance of the coating.

Design/methodology/approach

The main components of the conversion film include tannic acid, sodium molybdate and silane coupling agent KH560. After the preparation was completed, the samples were tested and analyzed, including surface morphology, conversion film components, bonding force with organic resins and corrosion resistance. Finally, it drew a conclusion that the conversion film can greatly improve the bonding strength of the steel substrate and epoxy resin.

Findings

When the content of tannic acid is 4 g/L meanwhile the content of KH560 is 20 g/L, the conversion film has the strongest binding force with epoxy resin, from 2.15 Mpa of untreated steel to 4.60 Mpa, growth of 140 per cent. At the same time, the resulting conversion film also improves the corrosion resistance of the steel surface by a small margin.

Originality/value

A method of enhancing the bond between an epoxy coating and steel is provided. Verify the mechanism of this method.
Enhanced corrosion resistance of Cr-Mn ASS by low temperature salt bath nitriding technique for the replacement of convectional Cr-Ni ASS
Authors: Tandon Vipin , Patil Awanikumar P. , Rathod Ramesh C.
Published: July 2019

Purpose

The purpose of this paper is to enhance the corrosion resistance of Cr-Mn austenitic stainless steel (ASS) via low temperature salt bath nitriding and to replace the convectional Cr-Ni ASS with newly developed enhanced corrosion resistive Cr-Mn ASS.

Design/methodology/approach

The low temperature salt bath nitriding was performed on Cr-Mn ASS at 450°C for 3 h in potassium nitrate salt bath.

Findings

The present paper compares the corrosion resistance of salt bath nitrided Cr-Mn ASS with convectional Cr-Ni ASSs (316 L and 304 L ASSs) in 3.5 per cent NaCl by electrochemical techniques. The electrochemical impedance spectroscopy result shows the increase in film resistance and potentiodynamic polarization results show the enhanced corrosion resistance of nitrided Cr-Mn ASS, which is almost equivalent to that of 316 L and 304 L ASSs. This is attributed to the formation of nitrogen supersaturated dense nitride layer. The present results therefore suggest that the nitrided Cr-Mn ASS may replace costly convectional Cr-Ni ASSs for commercial and industrial applications.

Originality/value

Ever-increasing price of nickel (Ni) is driving the industries to use Ni-free or low-Ni austenitic stainless steels (ASSs). But its corrosion resistance is relatively poor as compared to conventional Cr-Ni ASSs. However, its corrosion resistance can be improved by nitriding. The low temperature salt bath nitriding of Cr-Mn ASS and its electrochemical behavior in 3.5 per cent NaCl has not been studied. The present research paper is beneficial for industries to use low cost Cr-Mn, enhance its corrosion resistance and replace the use of costly conventional Cr-Ni ASSs.
Effect of microstructure on corrosion of welded joints of X80 steel in water saturated supercritical CO2
Authors: Deng Hongda , Cao Xianlong , Yan Yongbo , Xie Kuanya
Published: July 2019

Purpose

The purpose of this paper is to research whether microstructure varieties of zones at welded joints pose a tremendous effect on its corrosion in SC-CO2.

Design/methodology/approach

The interrelation between the corrosion and microstructure of base metal (BM), fine grain heat affected zone (FHAZ), coarse grain heat affected zone and weld metal (WM) in welded of X80 steel in water saturated supercritical CO2 was studied by using optical microscope, weight loss test, electrochemical measurements and surface analytical techniques.

Findings

The all subzones of X80 weld joints were attacked by SC-CO2 corrosion and showed flower-like corrosion scale spots consisted of granular FeCO3. The most severe corrosion appeared at WM due to lower proportion of ferrite to pearlite, but the slightest corrosion displayed at BM. GHAZ with larger grains and more polygonal ferrite exhibited more severe corrosion than that at BM. Due to its smaller grain, FHAZ displayed comparatively more severe corrosion to that at BM.

Originality/value

There exists close interrelation between the corrosion and microstructure of the welded carbon steel in water saturated supercritical CO2.
Impact of consultant obstetric presence on serious incidents
Authors: Shawer Sherif , Rowbotham Shirley , Heazell Alexander , Kelly Teresa , Vause Sarah
Published: July 2019

Purpose

Many organisations, including the Royal College of Obstetricians and Gynaecologists, have recommended increasing the number of hours of consultant obstetric presence in UK National Health Service maternity units to improve patient care. St Mary’s Hospital, Manchester implemented 24-7 consultant presence in September 2014. The paper aims to discuss these issues.

Design/methodology/approach

To assess the impact of 24-7 consultant presence upon women and babies, a retrospective review of all serious clinical intrapartum incidents occurring between September 2011 and September 2017 was carried out by two independent reviewers; disagreements in classification were reviewed by a senior Obstetrician. The impact of consultant presence was classified in a structure agreed a priori.

Findings

A total of 72 incidents were reviewed. Consultants were directly involved in the care of 75.6 per cent of cases before 24-7 consultant presence compared to 96.8 per cent afterwards. Negative impact due to a lack of consultant presence fell from 22 per cent of the incidents before 24-7 consultant presence to 9.7 per cent after implementation. In contrast, positive impact of consultant presence increased from 14.6 to 32.3 per cent following the introduction of 24-7 consultant presence.

Practical implications

Introduction of 24-7 consultant presence reduced the negative impact caused by a lack of, or delay in, consultant presence as identified by serious untoward incident (SUI) reviews. Consultant presence was more likely to have a positive influence on care delivery.

Originality/value

This is the first assessment of the impact of 24-7 consultant presence on the SUIs in obstetrics.
A wireless IOT system towards gait detection technique using FSR sensor and wearable IOT devices
Authors: Achanta Sampath Dakshina Murthy , T. Karthikeyan , R. Vinoth Kanna
Published: July 2019

Purpose

The recent advancement in gait analysis combines internet of things that provides better observations of person living behavior. The biomechanical model used for elderly and physically challenged persons is related to gait-related parameters, and the accuracy of the existing systems significantly varies according to different person abilities and their challenges. The paper aims to discuss these issues.

Design/methodology/approach

Deployment of wearable sensors in gait analysis provides a better solution while tracking the changes of the personal style, and this proposed model uses an electronics system using force sensing resistor and body sensors.

Findings

Experimental results provide an average gait recognition of 95 percent compared to the existing neural network-based gait analysis model based on the walking speeds and threshold values.

Originality/value

The sensors are used to monitor and update the predicted values of a person for analysis. Using IoT a communication process is performed in the research work by identifying a physically challenged person even in crowded areas.