bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival of White Spot Syndrome Virus–Infected Litopenaeus vannamei Fed with Ethanol Extract of Uncaria Tomentosa
Authors: Júnior Osmar Tomazelli , Kuhn Fernanda , Mendonça Padilha Paulo José , Mota Vicente Luiz R. , Winckler da Costa Sergio , Corrêa da Silva Bruno , Schleder Delano Dias , Nunes Nesi Cristiano , Dal Magro Jacir , de Lamo‐Castellví Sílvia
Published: November 2017

With the present project, the phytochemical composition of Uncaria tomentosa cultivated in Chapecó (Brazil) was analyzed and then the potential of using this local plant extract to protect by oral feeding virus‐infected Litopenaeus vannamei shrimp was also investigated. For this study, five treatments were tested: uninfected shrimp fed with pelleted feed (TC), WSSV‐infected shrimp fed with pelleted feed (T1), infected shrimp fed with pelleted feed with 1% ethanol extract of U. tomentosa (EEUT) (T2), infected shrimp fed with pelleted feed with 2% EEUT (T3), and infected shrimp fed pelleted feed with 4% EEUT (T4). The chemical analysis of EEUT showed the presence of alkaloids, flavonoids, sterols, terpenes, coumarins, and tannins and also a high in vitro free radical‐scavenging activity as well as high total phenolic content. Shrimp fed with 2 and 4% EEUT (T3 and T4) showed a survival probability significantly higher than T1 and T2 treatments and no clinical symptoms of WSSV infection. Immunological assay also showed a positive phenoloxidase activity effect on shrimp fed with EEUT.
Iron sucrose: assessing the similarity between the originator drug and its intended copies
Authors: Di Francesco Tiziana , Philipp Erik , Borchard Gerrit
Published: November 2017

Iron sucrose (IS) is a complex nanocolloidal intravenous suspension used in the treatment of iron‐deficiency anemia. Follow‐on IS products (iron sucrose similars (ISSs)) have obtained marketing authorization by the generic pathway, implying that identical copies of IS may be manufactured. However, recent prospective and retrospective clinical studies showed discrepancies in clinical outcomes, which might be related to differences in physicochemical properties. The aim of this work is to measure and compare the physicochemical properties of IS and three ISSs available in the market using innovative analytical procedures. The comprehensive elucidation of size, size distribution, morphology, and stability of these complex drugs revealed very significant differences between the products. This study serves to provide the basis to define critical quality attributes that may be linked to differences in clinical outcome and thus may contribute to an adequate regulatory approach for IS and its follow‐on products.
Compositional differences between Copaxone and Glatopa are reflected in altered immunomodulation ex vivo in a mouse model
Authors: Grossman Iris , Kolitz Sarah , Komlosh Arthur , Zeskind Benjamin , Weinstein Vera , Laifenfeld Daphna , Gilbert Adrian , Bar‐Ilan Oren , Fowler Kevin D. , Hasson Tal , Konya Attila , Wells‐Knecht Kevin , Loupe Pippa , Melamed‐Gal Sigal , Molotsky Tatiana , Krispin Revital , Papir Galia , Sahly Yousif , Hayden Michael R.
Published: November 2017

Copaxone (glatiramer acetate, GA), a structurally and compositionally complex polypeptide nonbiological drug, is an effective treatment for multiple sclerosis, with a well‐established favorable safety profile. The short antigenic polypeptide sequences comprising therapeutically active epitopes in GA cannot be deciphered with state‐of‐the‐art methods; and GA has no measurable pharmacokinetic profile and no validated pharmacodynamic markers. The study reported herein describes the use of orthogonal standard and high‐resolution physicochemical and biological tests to characterize GA and a U.S. Food and Drug Administration–approved generic version of GA, Glatopa (USA‐FoGA). While similarities were observed with low‐resolution or destructive tests, differences between GA and USA‐FoGA were measured with high‐resolution methods applied to an intact mixture, including variations in surface charge and a unique, high‐molecular‐weight, hydrophobic polypeptide population observed only in some USA‐FoGA lots. Consistent with published reports that modifications in physicochemical attributes alter immune‐related processes, genome‐wide expression profiles of ex vivo activated splenocytes from mice immunized with either GA or USA‐FoGA showed that 7–11% of modulated genes were differentially expressed and enriched for immune‐related pathways. Thus, differences between USA‐FoGA and GA may include variations in antigenic epitopes that differentially activate immune responses. We propose that the assays reported herein should be considered during the regulatory assessment process for nonbiological complex drugs such as GA.
A field test of commercial soil microbial treatments on native grassland restoration
Authors: Perkins Lora B. , Bennett Joe R.
Published: November 2017

Seedling establishment and performance are often limiting steps in many grassland restorations. The soil microbial community is thought to be a factor that contributes to the poor performance of seedlings. Therefore, we conducted a field test to examine the ability of four treatments to alter the soil microbial community and improve seedling performance during restoration. Treatments were commercially available bacterial inoculum, fungal inoculum, fungicide, and a bacteria/fungicide combination which were all designed and sold to enhance plant performance. We hypothesized that if the soil microbial community was limiting the performance of seedlings, then these products would remediate detrimental effects of the soil microbial community resulting in greater seedling performance. However, during the 2 years after restoration, no effect of the treatments was found. It is plausible that the treatments designed for agriculture or home garden settings were not appropriate for a wildland system.
An Assessment of the Cox Proportional Hazards Regression Model for Epidemiologic Studies
Authors: Moolgavkar Suresh H. , Chang Ellen T. , Watson Heather N. , Lau Edmund C.
Published: November 2017

The basic assumptions of the Cox proportional hazards regression model are rarely questioned. This study addresses whether hazard ratio, i.e., relative risk (RR), estimates using the Cox model are biased when these assumptions are violated. We investigated also the dependence of RR estimates on temporal exposure characteristics, and how inadequate control for a strong, time‐dependent confounder affects RRs for a modest, correlated risk factor. In a realistic cohort of 500,000 adults constructed using the National Cancer Institute Smoking History Generator, we used the Cox model with increasing control of smoking to examine the impact on RRs for smoking and a correlated covariate X. The smoking‐associated RR was strongly modified by age. Pack‐years of smoking did not sufficiently control for its effects; simultaneous control for effect modification by age and time‐dependent cumulative exposure, exposure duration, and time since cessation improved model fit. Even then, residual confounding was evident in RR estimates for covariate X, for which spurious RRs ranged from 0.980 to 1.017 per unit increase. Use of the Cox model to control for a time‐dependent strong risk factor yields unreliable RR estimates unless detailed, time‐varying information is incorporated in analyses. Notwithstanding, residual confounding may bias estimated RRs for a modest risk factor.
Should I Stay or Should I Go Now? Or Should I Wait and See? Influences on Wildfire Evacuation Decisions
Authors: McCaffrey Sarah , Wilson Robyn , Konar Avishek
Published: November 2017

As climate change has contributed to longer fire seasons and populations living in fire‐prone ecosystems increase, wildfires have begun to affect a growing number of people. As a result, interest in understanding the wildfire evacuation decision process has increased. Of particular interest is understanding why some people leave early, some choose to stay and defend their homes, and others wait to assess conditions before making a final decision. Individuals who tend to wait and see are of particular concern given the dangers of late evacuation. To understand what factors might influence different decisions, we surveyed homeowners in three areas in the United States that recently experienced a wildfire. The Protective Action Decision Model was used to identify a suite of factors previously identified as potentially relevant to evacuation decisions. Our results indicate that different beliefs about the efficacy of a particular response or action (evacuating or staying to defend), differences in risk attitudes, and emphasis on different cues to act (e.g., official warnings, environmental cues) are key factors underlying different responses. Further, latent class analysis indicates there are two general classes of individuals: those inclined to evacuate and those inclined to stay, and that a substantial portion of each class falls into the wait and see category.
Who is Policing the Community? A Comprehensive Review of Discrimination in Police Departments
Authors: Ray Victor , Ortiz Kasim , Nash Jacob
Published: November 2017

This paper is a systematic review of the literature on diversity in police forces. We focus on four main empirical domains that have received the bulk of the attention in the literature 1) recruitment 2) hiring, 3) promotion, 4) organizational contexts. We argue that this literature would be better served by integrating findings into the emerging theoretical framework of racialized organizations theory (Ray et al. 2017) which sees organizations as a key meso‐level factor reproducing both individual and state level racial inequality. Building from here, we described our methodological approach for systematically reviewing the extant literature and present our findings. Lastly, we conclude with highlighting sociopolitical and policy implications uncovered by our findings, for contemporary American policing.
The Totality of States of Affairs and the Minimal Truthmaker
Authors: Zamani Mohsen
Published: November 2017

Armstrong appeals to the existence of totalities in order to solve the problem of negative truths. The totality of first‐order states of affairs is a truthmaker for all negative truths, but it involves things which are irrelevant to many such truths. To solve this problem, Armstrong claimed that negative truths have minimal truthmakers which usually consist in totalities smaller than the totality of first‐order states of affairs. Merricks objects to this claim by arguing that given Armstrong’s definition of minimal truthmakers, the totality of first‐order states of affairs is a minimal truthmaker for every negative truth. In this article, I respond to Merricks’s objection. I will first show that the definition of minimal truthmakers that he proposes is not plausible. However, Merricks’s objection, I will argue, also works on the standard definition of minimal truthmakers. I will then show that for independent reasons, the standard definition should be revised, and, given my revised definition, Merricks’s objection fails.
Two‐stage identification ofSNPeffects on dynamic poplar growth
Authors: Liu Jingyuan , Ye Meixia , Zhu Sheng , Jiang Libo , Sang Mengmeng , Gan Jingwen , Wang Qian , Huang Minren , Wu Rongling
Published: November 2017

This project proposes an approach to identify significant single nucleotide polymorphism (SNP) effects, both additive and dominant, on the dynamic growth of poplar in diameter and height. The annual changes in yearly phenotypes based on regular observation periods are considered to represent multiple responses. In total 156,362 candidateSNPs are studied, and the phenotypes of 64 poplar trees are recorded. To address this ultrahigh dimensionality issue, this paper adopts a two‐stage approach. First, the conventional genome‐wide association studies (GWAS) and the distance correlation sure independence screening (DC‐SIS) methods (Liet al., 2012) were combined to reduce the model dimensions at the sample size; second, a grouped penalized regression was applied to further refine the model and choose the final sparseSNPs. The multiple response issue was also carefully addressed. TheSNPeffects on the dynamic diameter and height growth patterns of poplar were systematically analyzed. In addition, a series of intensive simulation studies was performed to validate the proposed approach.
EFFECT OF TIP CLEARANCE ON THE FLOW FIELD OF THE MIXED FLOW TURBOCHARGER TURBINE
Authors: Kamarudin M. S. , Zulkeflee M. , Padzillah M. H.
Published: November 2017

Turbocharger is a device comprising mainly of a turbine and a compressor. The demand of turbocharger in the automotive industry increases as it significantly enhances the output power of an Internal Combustion Engine and reduces emission. The use of mixed flow turbine to replace the conventional radial turbine gives better impact since the turbine transient response increases and operates more efficiently at low velocity ratio. The flow behaviour inside the turbine affects the torque generation by the turbine. It is necessary for the turbine to have a specified clearance between the rotor tip and the casing of the turbomachine. This undoubtedly will contribute to clearance loss and mixing of leaked flow which produce disturbance to the exhaust flow. In order to investigate this effect, the validated Computational Fluid Dynamics method is chosen in order to replicate the flow field inside the mixed flow turbine. The simulation is carried out at the optimum operating condition which is at turbine total-to-static efficiency of 79% with inlet mass flow rate of 0.5kg/s. The flow inside the passage is plotted into pressure and velocity contours which are compared at 50% (30000rpm) and 80% (48000rpm) of the turbine design speed. The comparison between having 0% (no leakage) and 3% shroud tip clearance are then compared. Through the analysis, it is suggested that clearance leakage and flow separation cause disruption to the desirable uniform flow inside the turbine passage. The presence of Coriolis effect that resists the clearance leakage flow only at near leading edge of the rotor is observed. Furthermore, a low pressure region is perceived at rotor hub which absent in the radial flow turbine. These factors eventually reduce the performances of the actual turbine.
The Lumped Capacitance Model for Unsteady Heat Conduction in Regular Solid Bodies With Natural Convection to Nearby Fluids Engages the Nonlinear Bernoulli Equation
Authors: Campo Antonio
Published: November 2017

For the analysis of unsteady heat conduction in solid bodies comprising heat exchange by forced convection to nearby fluids, the two feasible models are (1) the differential or distributed model and (2) the lumped capacitance model. In the latter model, the suited lumped heat equation is linear, separable, and solvable in exact, analytic form. The linear lumped heat equation is constrained by the lumped Biot number criterion Bil=h¯(V/S)/ks < 0.1, where the mean convective coefficient h¯ is affected by the imposed fluid velocity. Conversely, when the heat exchange happens by natural convection, the pertinent lumped heat equation turns nonlinear because the mean convective coefficient h¯ depends on the instantaneous mean temperature in the solid body. Undoubtedly, the nonlinear lumped heat equation must be solved with a numerical procedure, such as the classical Runge–Kutta method. Also, due to the variable mean convective coefficient h¯ (T), the lumped Biot number criterion Bil=h¯(V/S)/ks < 0.1 needs to be adjusted to Bil,max=h¯max(V/S)/ks < 0.1. Here, h¯max in natural convection cooling stands for the maximum mean convective coefficient at the initial temperature Tin and the initial time t = 0. Fortunately, by way of a temperature transformation, the nonlinear lumped heat equation can be homogenized and later channeled through a nonlinear Bernoulli equation, which admits an exact, analytic solution. This simple route paves the way to an exact, analytic mean temperature distribution T(t) applicable to a class of regular solid bodies: vertical plate, vertical cylinder, horizontal cylinder, and sphere; all solid bodies constricted by the modified lumped Biot number criterion Bil,max<0.1.
A Numerical Study on Electrowetting-Induced Droplet Detachment From Hydrophobic Surface
Authors: Islam Md Ashraful , Tong Albert Y.
Published: November 2017

Electrowetting-induced microwater droplet detachment from hydrophobic surface has been studied numerically. The governing equations for transient microfluidic flow are solved by a finite volume scheme with a two-step projection method on a fixed computational domain. The free surface of the droplet is tracked by the volume-of-fluid method with the surface tension force determined by the continuum surface force (CSF) model. The static contact angle has been implemented using a wall-adhesion boundary condition at the solid–liquid interface, while the dynamic contact angle is computed assuming a fixed deflection from the static contact angle. The results of the numerical model have been validated with published experimental data and the physics of stretching, recoiling, and detachment of the droplet have been investigated. A parametric study has been performed in which the effects of droplet volume, voltage amplitude, and voltage pulse width have been examined.
Effects of Real Gas Model Accuracy and Operating Conditions on Supercritical CO2 Compressor Performance and Flow Field
Authors: Ameli Alireza , Afzalifar Ali , Turunen-Saaresti Teemu , Backman Jari
Published: November 2017

Rankine and Brayton cycles are common energy conversion cycles and constitute the basis of a significant proportion of global electricity production. Even a seemingly marginal improvement in the efficiency of these cycles can considerably decrease the annual use of primary energy sources and bring a significant gain in power plant output. Recently, supercritical Brayton cycles using CO2 as the working fluid have attracted much attention, chiefly due to their high efficiency. As with conventional cycles, improving the compressor performance in supercritical cycles is major route to increasing the efficiency of the whole process. This paper numerically investigates the flow field and performance of a supercritical CO2 centrifugal compressor. A thermodynamic look-up table is coupled with the flow solver, and the look-up table is systematically refined to take into account the large variation of thermodynamic properties in the vicinity of the critical point. Effects of different boundary and operating conditions are also discussed. It is shown that the compressor performance is highly sensitive to the look-up table resolution as well as the operating and boundary conditions near the critical point. Additionally, a method to overcome the difficulties of simulation close to the critical point is explained.
Evaluation of Youth Enjoyment Toward Physical Activity and Sedentary Behavior
Authors: Bai Yang , Allums-Featherston Kelly , Saint-Maurice Pedro F. , Welk Gregory J. , Candelaria Norma
Published: November 2017

Purpose: The consensus is that physical activity (PA) and sedentary behavior (SB) are independent behaviors, but past findings suggest that they may be influenced by common underlying factors. To clarify this issue, we examined associations between enjoyment of PA and participation in both PA and SB in a large sample of 4th- to 12th-grade US youth. Methods: A total of 18,930 students from 187 schools completed the youth activity profile, a self-report 15-item survey that assesses time spent in PA and SB in school and home settings. Two additional items captured enjoyment of PA and physical education. Two-way (gender × enjoyment and grade × enjoyment) mixed analysis of variances were conducted. Results: Pearson correlation results revealed a positive relationship between enjoyment and PA (r = .38, P < .05) and an inverse correlation between enjoyment and SB (r = −.23, P < .05). Statistically significant main effects of enjoyment were found in the 2-way analysis of variance for both PA and SB. The simple main effect from analysis of variance indicated students with high enjoyment of PA reported higher levels of PA and lower levels of SB compared with students reporting moderate or low levels of enjoyment. Conclusion: The results provide new insights related to the relevance of enjoyment as a common underlying variable influencing both PA and SB across gender and grade levels.
Networks of global bird invasion altered by regional trade ban
Authors: Reino Luís , Figueira Rui , Beja Pedro , Araújo Miguel B. , Capinha César , Strubbe Diederik
Published: November 2017

European Union’s ban on trade in wild-caught birds both reduces and redistributes bird invasion risk globally.
Seismic potential of weak, near-surface faults revealed at plate tectonic slip rates
Authors: Ikari Matt J. , Kopf Achim J.
Published: November 2017

Experimental shearing at plate rate speeds reveals slow slip events and earthquake potential on weak, shallow faults.
Tougher than hell
Authors: Voosen Paul
Published: November 2017

Transistors that thrive on heat and pressure could take spacecraft to the surface of Venus.
Structural insights into ion conduction by channelrhodopsin 2
Authors: Volkov Oleksandr , Kovalev Kirill , Polovinkin Vitaly , Borshchevskiy Valentin , Bamann Christian , Astashkin Roman , Marin Egor , Popov Alexander , Balandin Taras , Willbold Dieter , Büldt Georg , Bamberg Ernst , Gordeliy Valentin
Published: November 2017

The inner workings of an optogenetic tool

Channelrhodopsins are membrane channel proteins whose gating is controlled by light. In their native setting, they allow green algae to move in response to light. Their expression in neurons allows precise control of neural activity, an approach known as optogenetics. Volkov
et al.
describe the high-resolution structure of channelrhodopsin 2, the most widely used optogenetics tool, as well as the structure of a mutant with a longer open-state lifetime (see the Perspective by Gerwert). Light activation perturbs an intricate hydrogen-bonding network to open the channel. The structures provide a basis for designing better optogenetic tools.

Science
, this issue p.
10.1126/science.eaan8862
; see also p.
1000
Multifunctional biohybrid magnetite microrobots for imaging-guided therapy
Authors: Yan Xiaohui , Zhou Qi , Vincent Melissa , Deng Yan , Yu Jiangfan , Xu Jianbin , Xu Tiantian , Tang Tao , Bian Liming , Wang Yi-Xiang J. , Kostarelos Kostas , Zhang Li
Published: November 2017

A biohybrid microrobot with one-step fabrication provides multiple functions for imaging-guided therapy.
Complete Genome Sequence of the Novel Bacteriophage pSco-10 Infecting Staphylococcus cohnii
Authors: Jun Jin Woo , Giri Sib Sankar , Kim Hyoun Joong , Chi Cheng , Yun Saekil , Kim Sang Guen , Kim Sang Wha , Kang Jeong Woo , Park Se Chang
Published: November 2017

Herein, we report the complete genome sequence of the
Staphylococcus Myoviridae
phage pSco-10 infecting
Staphylococcus cohnii
. The phage pSco-10 was isolated from duck feces collected from four farms in South Korea. The current report provides valuable information for genomic study of phages.
Whole-Genome Sequencing of Lactobacillus salivarius Strains BCRC 14759 and BCRC 12574
Authors: Chiu Shih-Hau , Chen Chien-Chi , Wang Li-Ting , Huang Lina
Published: November 2017

Lactobacillus salivarius
BCRC 14759 has been identified as a high-exopolysaccharide-producing strain with potential as a probiotic or fermented dairy product. Here, we report the genome sequences of
L. salivarius
BCRC 14759 and the comparable strain BCRC 12574, isolated from human saliva. The PacBio RSII sequencing platform was used to obtain high-quality assemblies for characterization of this probiotic candidate.
Genomic Characterization of the First Equine-Like G3P[8] Rotavirus Strain Detected in the United States
Authors: Perkins Charity , Mijatovic-Rustempasic Slavica , Ward M. Leanne , Cortese Margaret M. , Bowen Michael D.
Published: November 2017

We report here the full coding region sequences for all 11 segments of the first equine-like G3P[8] rotavirus strain detected in the United States, strain RVA/Human-wt/USA/3000390639/2015/G3P[8]. The full genotype constellation of this strain is G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2.
Complete Genome Sequence of the Predatory Bacterium Ensifer adhaerens Casida A
Authors: Williams Laura E. , Baltrus David A. , O’Donnell Sean D. , Skelly Tara J. , Martin Mark O.
Published: November 2017

We report here the complete genome sequence of the facultative predatory bacterium
Ensifer adhaerens
strain Casida A. The genome was assembled into three circular contigs, with a main chromosome as well as two large secondary replicons, that totaled 7,267,502 bp with 6,641 predicted open reading frames.
Complete Genome Sequence of Collinsella aerofaciens Isolated from the Gut of a Healthy Indian Subject
Authors: Bag Satyabrata , Ghosh Tarini Shankar , Das Bhabatosh
Published: November 2017

Collinsella aerofaciens
, a rod-shaped nonmotile obligate anaerobe, is the most abundant actinobacterium in the gastrointestinal tract of healthy humans. An altered abundance of
C. aerofaciens
may be linked with several health disorders, including irritable bowel syndrome. In the present study, we report the complete genome sequence of
C. aerofaciens
strain indica.
Repression of YdaS Toxin Is Mediated by Transcriptional Repressor RacR in the Cryptic
rac
Prophage of Escherichia coli K-12
Authors: Krishnamurthi Revathy , Ghosh Swagatha , Khedkar Supriya , Seshasayee Aswin Sai Narain
Published: November 2017

Transcription factors in the bacterium
E. coli
are rarely essential, and when they are essential, they are largely toxin-antitoxin systems. While studying transcription factors encoded in horizontally acquired regions in
E. coli
, we realized that the protein RacR, a putative transcription factor encoded by a gene on the
rac
prophage, is an essential protein. Here, using genetics, biochemistry, and bioinformatics, we show that its essentiality derives from its role as a transcriptional repressor of the
ydaS
and
ydaT
genes, whose products are toxic to the cell. Unlike type II toxin-antitoxin systems in which transcriptional regulation involves complexes of the toxin and antitoxin, repression by RacR is sufficient to keep
ydaS
transcriptionally silent.
Genomic, Network, and Phylogenetic Analysis of the Oomycete Effector Arsenal
Authors: McGowan Jamie , Fitzpatrick David A.
Published: November 2017

The oomycetes are a class of microscopic, filamentous eukaryotes and include ecologically significant animal and plant pathogens. Oomycetes secrete large arsenals of effector proteins that degrade host cell components, manipulate host immune responses, and induce necrosis, enabling parasitic colonization. In this study, we catalogued the number and evolution of effectors in 37 oomycete species whose genomes have been completely sequenced. Large expansions of effector protein families inPhytophthoraspecies, including glycoside hydrolases, pectinases, and necrosis-inducing proteins, were observed. Species-specific expansions were detected, including chitinases inAphanomyces astaciandPythium oligandrum. Novel effectors which may be involved in suppressing animal immune responses were identified inAp. astaciandPy. oligandrum. Type 2 necrosis-inducing proteins with an unusual phylogenetic history were also located. This work represents an up-to-datein silicocatalogue of the effector arsenal of the oomycetes based on the 37 genomes currently available.
A Simple and Universal System for Gene Manipulation in Aspergillus fumigatus:
In Vitro
-Assembled Cas9-Guide RNA Ribonucleoproteins Coupled with Microhomology Repair Templates
Authors: Al Abdallah Qusai , Ge Wenbo , Fortwendel Jarrod R.
Published: November 2017

Tackling the multifactorial nature of virulence and antifungal drug resistance in
A. fumigatus
requires the mechanistic interrogation of a multitude of genes, sometimes across multiple genetic backgrounds. Classical fungal gene replacement systems can be laborious and time-consuming and, in wild-type isolates, are impeded by low rates of homologous recombination. Our simple and universal CRISPR-Cas9 system for gene manipulation generates efficient gene targeting across different genetic backgrounds of
A. fumigatus
. We anticipate that our system will simplify genome editing in
A. fumigatus
, allowing for the generation of single- and multigene knockout libraries. In addition, our system will facilitate the delineation of virulence factors and antifungal drug resistance genes in different genetic backgrounds of
A. fumigatus
.
CRISPR-Cas-Mediated Gene Silencing Reveals RacR To Be a Negative Regulator of YdaS and YdaT Toxins in Escherichia coli K-12
Authors: Bindal Gargi , Krishnamurthi Revathy , Seshasayee Aswin Sai Narain , Rath Devashish
Published: November 2017

racR
is an essential gene and one of the many poorly studied genes found on the
rac
prophage element that is present in many
Escherichia coli
genomes. Employing a CRISPR-based approach, we have silenced
racR
expression to various levels and elucidated its physiological consequences. We show that the downregulation of
racR
leads to upregulation of the adjacent
ydaS-ydaT
operon. Both YdaS and YdaT act as toxins by perturbing the cell division resulting in enhanced cell killing. This work establishes a physiological role for RacR, which is to keep the toxic effects of YdaS and YdaT in check and promote cell survival. We, thus, provide a rationale for the essentiality of
racR
in
Escherichia coli
K-12 strains.
Thoracic aortic transection resulting in a type B dissection following blunt trauma
Authors: Fogleman Lance , Caffery Terrell , Gruner Jeffrey , Tatum Danielle
Published: November 2017

A 39-year-old man sustained an acute grade III aortic injury resulting in a type B aortic dissection in the setting of severe traumatic brain injury, cervical spine injury and multiple orthopaedic injuries following a motorcycle crash. The patient underwent an emergent thoracic endovascular aortic repair, complicated by a thoracic pseudoaneurysm rupture and ongoing exsanguination from a persistent type 1 endoleak. Additional stent grafts were required to gain control of the endoleak. The patient ultimately progressed to brain death post procedure in the intensive care unit. This case reviews treatment considerations in the context of a blunt thoracic aortic transection and distal dissection with concomitant polytrauma.
Impact of multimorbidity on healthcare professional task shifting potential in patients with type 2 diabetes in primary care: a French cross-sectional study
Authors: Supper Irène , Bourgueil Yann , Ecochard René , Letrilliart Laurent
Published: November 2017

Objectives

To estimate the transferability of processes of care from general practitioners (GPs) to allied healthcare professionals and the determinants of such transferability.

Design

French national cross-sectional multicentre study

Setting

128 family practices providing supervised training for residents in general practice.

Participants

All patients consulting with their GP over a total number of 20 days (ie, 1 day a week from December 2011 to April 2012). Encounters where type 2 diabetes was one of the managed health problems were selected for analysis.

Primary and secondary outcome measures

Processes that were associated with specific health problems were collected by 54 residents. Potential process transferability was the main outcome assessed, as well as the professionals involved in the collaboration and the eventual conditions associated with transfer.

Results

From 8572 processes of care that concerned 1088 encounters of patients with diabetes, 21.9% (95% CI 21.1% to 22.8%) were considered eligible for transfer from GPs to allied healthcare professionals (78.1% to nurses, 36.7% to pharmacists). Processes were transferable with condition(s) for 70.6% (ie, a protocol, shared record or supervision). The most transferable processes concerned health maintenance (32.1%) and cardiovascular risk factors (hypertension (28.7%), dyslipidaemia (25.3%) and diabetes (24.3%)). Multivariate analysis showed that educational processes or a long-term condition status were associated with increased transferability (OR 3.26 and 1.47, respectively), whereas patients with higher intellectual occupations or those with two or more associated health problems were associated with lower transferability (OR 0.33 and 0.81, respectively).

Conclusions

A significant part of GP activity relating to patients with multimorbidity including type 2 diabetes could be transferred to allied healthcare professionals, mainly on prevention and global education to cardiovascular risk factors. The organisational and finance conditions of team work as views of patients and healthcare professionals must be explored before implementation in primary care.
Use of a primary care online consultation system, by whom, when and why: evaluation of a pilot observational study in 36 general practices in South West England
Authors: Edwards Hannah B , Marques Elsa , Hollingworth William , Horwood Jeremy , Farr Michelle , Bernard Elly , Salisbury Chris , Northstone Kate
Published: November 2017

Objectives

Evaluation of a pilot study of an online consultation system in primary care. We describe who used the system, when and why, and the National Health Service costs associated with its use.

Design

15-month observational study.

Setting

Primary care practices in South West England.

Results

36 General practices covering 396 828 patients took part in the pilot. The online consultation website was viewed 35 981 times over the pilot period (mean 9.11 visits per 1000 patients per month). 7472 patients went on to complete an ‘e-consultation’ (mean 2.00 online consultations per 1000 patients per month). E-consultations were mainly performed on weekdays and during normal working hours. Patient records (n=485) were abstracted for eight practices and showed that women were more likely to use e-consultations than men (64.7% vs 35.3%) and users had a median age of 39 years (IQR 30–50). The most common reason for an e-consultation was an administrative request (eg, test results, letters and repeat prescriptions (22.5%)) followed by infections/immunological issues (14.4%). The majority of patients (65.2%) received a response within 2 days. The most common outcome was a face-to-face (38%) or telephone consultation (32%). The former were more often needed for patients consulting about new conditions (OR 1.56, 95% CI 1.05 to 2.27, p=0.049). The average cost of a practice’s response to an e-consultation was £36.28, primarily triage time and resulting face-to-face/telephone consultations needed.

Conclusions

Use of e-consultations is very low, particularly at weekends. Unless this can be improved, any impact on staff workload and patient waiting times is likely to be negligible. It is possible that use of e-consultations increases primary care workload and costs. Online consultation systems could be developed to improve efficiency both for staff and patients. These findings have implications for software developers as well as primary care services and policy-makers who are considering investing in online consultation systems.
Authorship, plagiarism and conflict of interest: views and practices from low/middle-income country health researchers
Authors: Rohwer Anke , Young Taryn , Wager Elizabeth , Garner Paul
Published: November 2017

Objectives

To document low/middle-income country (LMIC) health researchers’ views about authorship, redundant publication, plagiarism and conflicts of interest and how common poor practice was in their institutions.

Design

We developed a questionnaire based on scenarios about authorship, redundant publication, plagiarism and conflicts of interest. We asked participants whether the described practices were acceptable and whether these behaviours were common at their institutions. We conducted in-depth interviews with respondents who agreed to be interviewed.

Participants

We invited 607 corresponding authors of Cochrane reviews working in LMICs. From the 583 emails delivered, we obtained 199 responses (34%). We carried out in-depth interviews with 15 respondents.

Results

Seventy-seven per cent reported that guest authorship occurred at their institution, 60% reported text recycling. For plagiarism, 12% of respondents reported that this occurred ‘occasionally’, and 24% ‘rarely’. Forty per cent indicated that their colleagues had not declared conflicts of interest in the past. Respondents generally recognised poor practice in scenarios but reported that they occurred at their institutions. Themes identified from in-depth interviews were (1) authorship rules are simple in theory, but not consistently applied; (2) academic status and power underpin behaviours; (3) institutions and culture fuel bad practices and (4) researchers are uncertain about what conflict of interests means and how this may influence research.

Conclusions

LMIC researchers report that guest authorship is widely accepted and common. While respondents report that plagiarism and undeclared conflicts of interest are unacceptable in practice, they appear common. Determinants of poor practice relate to academic status and power, fuelled by institutional norms and culture.
Ten essential papers for the practice of evidence-based medicine
Authors: Nunan David , O’Sullivan Jack , Heneghan Carl , Pluddemann Annette , Aronson Jeffrey , Mahtani Kamal
Published: November 2017

In this article we signpost readers to 10 papers we consider essential reading for anyone starting out on an evidence-based medicine journey. We have considered papers consisting a mix of old and new, seminal and cutting-edge that offer insight into what evidence-based medicine is, where it came from, why it matters and what it has achieved. This is balanced against some of the common criticisms of evidence-based medicine and efforts to tackle them. We have also highlighted papers acknowledging the importance of teaching and learning of the principles of evidence-based medicine and how health professionals can better use evidence in clinical decisions with patients.
1 Patient acceptability and feasibility of HIV testing in emergency departments in the UK – a systematic review and meta-analysis
Authors: Lungu Nicola
Published: November 2017

Background

NICE 2016 HIV testing guidelines now include the recommendation to offer HIV testing in Emergency Departments, in areas of high prevalence,1to everyone who is undergoing blood tests. 23% of England’s local authorities are areas of high HIV prevalence (>2/1000) and are therefore eligible.2So far very few Emergency Departments have implemented routine HIV testing. This systematic review assesses evidence for two implementation considerations: patient acceptability (how likely a patient will accept an HIV test when offered in an Emergency Department), and feasibility, which incorporates staff training and willingness, and department capacity, (how likely Emergency Department staff will offer an HIV test to an eligible patient), both measured by surrogate quantitative markers.

Methods and results

Three medical databases were systematically searched for reports of non-targeted HIV testing in UK Emergency Departments. A total of 1584 unique papers were found, 9 full text articles were critically appraised, and 7 studies included in meta-analysis. There is a combined patient sample of 1 01 975. The primary outcome, patient acceptability of HIV testing in Emergency Departments (number of patients accepting an HIV test, as a proportion of those offered) is 54.1% (CI 40.1, 68.2). Feasibility (number of tests offered, as a proportion of eligible patients) is 36.2% (CI 9.8, 62.4).

Conclusions

For an Emergency Department considering introducing routine HIV testing, this review suggests an opt-out publicity-lead strategy. Utilising oral fluid and blood tests would lead to the greatest proportion of eligible patients accepting an HIV test. For individual staff who are consenting patients for HIV testing, it may be encouraging to know that there is >50% chance the patient will accept an offer of testing.

Table 1

Summary table of data extracted from final 7 studies, with calculated acceptability and feasibility if appropriate, and GRADE score. Studies listed in chronological order of data collection. GRADE working group evidence grades: 4= high quality, 3= moderate quality, 2= low quality, 1 or below = very low quality. (*study conclusion reports this figure is inaccurate)

Figure 1

Patients accepting HIV tests, and being offered HIV tests, as a proportion of the eligible sample

References

National Institute for Health and Care Excellence, Public Health England.HIV testing: Increasing uptake among people who may have undiagnosed HIV. 2016 1 December 2016.

Public Health England.HIV prevalence by Local Authority of residence to end December 2015. Table No.1: 2016. Public Health Engand; 2016.
10 Decision analysis modelling of diagnostic strategies for suspected pulmonary embolism in pregnancy: the DiPEP economic evaluation
Authors: Pollard Daniel , Goodacre Steve , Stevenson Matthew , Fuller Gordon
Published: November 2017

Background

Using diagnostic imaging for suspected pulmonary embolism (PE) in pregnancy involves weighing the benefits, harms and costs of different approaches to selecting women for imaging.

Objectives

To estimate the effectiveness of diagnostic strategies for PE in pregnancy and postpartum, in terms of adverse outcomes from venous thromboembolism, bleeding and radiation exposure, and cost effectiveness, measured as the incremental cost per quality-adjusted life year (QALY).

Methods

Decision-analysis modelling was used to estimate costs incurred and expected outcomes from thromboembolism, bleeding and radiation exposure if a hypothetical cohort of pregnant or postpartum women based on the Diagnosis of PE in Pregnancy (DiPEP) study population were investigated for suspected PE using different strategies, including no imaging, selective imaging based on a clinical decision rule and imaging for all. Outcomes were modelled to estimate the quality-adjusted life years (QALYs) accrued by each strategy and the incremental cost per QALY gained by each strategy compared to the next most effective alternative. Threshold analysis explored the parameters required for a hypothetical clinical decision rule to be cost-effective.

Results

Decision analysis showed that a nonselective strategy of scanning all women with suspected PE accrued more QALYs and incurred fewer costs than any selective strategy based on a clinical decision rule and was therefore the dominant strategy. This finding was robust in sensitivity analysis and scenario analysis exploring assumptions in the model. Threshold analysis showed that a clinical decision rule to select women for imaging would need to have sensitivity exceeding 97.5% to be cost-effective compared to nonselective use of scanning.

Figure 1

Conclusion

There is little potential for selective imaging based on a clinical decision rule to be cost-effective compared to a strategy of nonselective imaging for all women with suspected PE in pregnancy and postpartum.
11 Topical nsaids for analgesia in traumatic corneal abrasions: a systematic review and meta-analysis
Authors: Lawrenson Annali , Wakai Abel
Published: November 2017

Background

Traumatic corneal abrasions are common ocular presenTations in the ED. There is no consensus regarding the most appropriate analgesia for this condition. Topical non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as pain-relief to minimise systemic adverse events associated with oral analgesia.

Aim

To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time.

Methods

We searched MEDLINE, EMBASE, Cochrane Library and clinical trials registers up to 30/03/17. We did not use any date or language restrictions in the electronic searches for trials. We checked the reference lists of identified trials to search for further potentially relevant studies. Two review authors independently performed data extraction and assessed risks of bias in the included studies. We assessed risk of bias using the Cochrane risk of bias tool and rated the certainty of the evidence using GRADE.

Results

We included nine studies that met the inclusion criteria, reporting data on 637 participants. These studies compared five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) to control (consisting of standard care and in four studies used placebo eye drops). Overall, the studies were at an unclear or high risk of bias (particularly selection and reporting bias). None of the included studies reported the primary outcome measures of this review, namely participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials, that included data on 481 participants receiving NSAIDs or control (placebo/standard care), reported on the use of ‘rescue’ analgesia at 24 hours as a proxy measure of pain control. Topical NSAIDs were associated with a reduction in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4 out of 10 people in the control group used rescue analgesia at 24 hours. No data were available on the use of analgesia at 48 or 72 hours. There was no evidence from the included trials of an effect of topical NSAIDS on healing time and possible drug-related adverse events were low and balanced across intervention and control groups.

Conclusions

The findings of the included studies do not provide strong evidence to support the use.
12 A multi-centre randomised feasibility study evaluating the impact of a prognostic model for management of blunt chest wall trauma patients: stumbl trial
Authors: Battle Ceri , Hutchings Hayley , Abbott Zoe , O’neill Claire , Groves Sam , Watkins Alan , Lecky Fiona , Jones Sally , Gagg James , Body Rick , Evans Phillip
Published: November 2017

Introduction

A new prognostic model has been developed and externally validated, the aim of which is to assist in the management of the blunt chest wall trauma patient in the Emergency Department (ED). A definitive randomised controlled trial (impact trial), is required to assess the clinical and cost effectiveness of the new model, before it can be accepted in clinical practice. The purpose of this trial is to assess the feasibility and acceptability of such a definitive trial and inform its design.

Methods and analysis

This feasibility trial is designed to test the methods of a multi-centre, cluster-randomised (stepped wedge) trial, with a substantial qualitative component. Four EDs in England and Wales will collect data for all blunt chest wall trauma patients over a five month period; in the initial period acting as the controls (normal care) and the second period, acting as the interventions (in which the new model will be used). Baseline measurements including completion of the SF-12v2 will be obtained on initial assessment in the ED. Patient outcome data will then be collected for any subsequent hospitalisations. Data collection will conclude with a six week follow-up completion of two surveys (SF-12v2 and Client Services Receipt Inventory).

Analysis of outcomes will focus on feasibility, acceptability and trial processes and will include recruitment and retention rates, attendance at clinician training rates and use of model in the ED. Qualitative feedback will be obtained through clinician interviews and a research nurse focus group. An evaluation of the feasibility of health economics outcomes data will be completed.

Ethics and dissemination

Wales Research Ethics Committee 6 granted approval for the trial in September 2016. Health Care Research Wales Research Permissions and the HRA have granted approval for the study. Patient recruitment commenced in February 2017. Planned dissemination is through publication in a peer-reviewed Emergency Medicine Journal, presentation at appropriate conferences and to stakeholders at Professional Meetings.