bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonization with extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae in solid organ transplantation: A meta‐analysis and review
Authors: Alevizakos Michail , Kallias Athanasios , Flokas Myrto Eleni , Mylonakis Eleftherios
Published: May 2017

Background

Extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae (ESBL‐E) may cause severe infections, often preceded by ESBL‐E gastrointestinal (GI) colonization.

Methods

We conducted a review of the literature, investigating the prevalence of ESBL‐E GI colonization in solid organ transplant (SOT) patients and the risk for subsequent ESBL‐E infection. We searched the PubMed and EMBASE databases (to April 1, 2016) looking for studies that contained data on ESBL‐E colonization among transplant patients.

Results

Of 341 non‐duplicate citations, four studies reporting data on 1089 patients fulfilled our inclusion criteria. Among them, the pooled prevalence for ESBL‐E colonization was 18% (95% confidence interval [CI] 5%‐36%). Stratifying by transplant type, we identified an ESBL‐E colonization rate of 17% (95% CI 3%‐39%) among liver transplant recipients and 24% (single report) among kidney transplant recipients.

Conclusions

Among SOT patients, approximately one in five patients is colonized with ESBL‐E, although this finding may be skewed by reporting bias from centers with high ESBL‐E prevalence. ESBL‐E screening in SOT patients should be considered and evaluated in future studies.
From total blood exchange to erythrocytapheresis and back to treat complications of sickle cell disease
Authors: Ballas Samir K.
Published: May 2017

Erythrocytapheresis is an important procedure in the management of certain complications of sickle cell disease, including acute stroke, stroke prevention, acute chest syndrome, and multiorgan failure. Erythrocytapheresis in sickle cell disease simply entails the removal of the patient's red blood cells containing the abnormal sickle hemoglobin and replacing them with normal red blood cells carrying normal hemoglobin. In these procedures, the patient's plasma is not exchanged but is returned to the patient. Several studies have demonstrated that the plasma of patients with sickle cell disease contains several components that increase blood viscosity and initiate or promote vaso‐occlusion. These factors include increased levels of globulins, especially immunoglobulin G, acute‐phase reactants, fibrinogen, coagulation factors, inflammatory mediators, and heme in the steady state and increase further during painful crises. This may explain why, in certain complications of sickle cell disease, such as acute chest syndrome, hepatic crisis, and priapism, erythrocytapheresis by itself may not be effective despite repetitive cycles of red blood cell exchange. The use of therapeutic plasma exchange in addition to erythrocytapheresis in these situations seems to be useful in resolving them more efficiently. The role of therapeutic plasma exchange in the management of certain complications of sickle cell disease needs further evaluation. This commentary addresses the role of therapeutic plasma exchange in the management of complications of sickle cell disease.
The Imperial Condition of Photography in Palestine: Archives, Looting, and the Figure of the Infiltrator
Authors: Azoulay Ariella
Published: May 2017

In front of many cameras and representatives of the international community that surround him, unexpectedly, and outside of any protocol that was prepared for this occasion, an elderly Palestinian man dares to stop, to withdraw his consent to leave his home and ceases to move. This old man is my companion in exploring the archives and attempting to understand its implication in the invention of the figure of “infiltrator.” Together, we refrain from studying his figure, as defined by the nation‐state that forced him out of his home. Halting precisely where many cameras were present, this person threatens to spoil the orchestrated spectacle of Arabs “leaving of their will.” Together, we study the linkage between the expulsion of several hundred thousands of Palestinians and the looting of a vast treasure of books, documents, and photographs from Palestinians in 1948 and their transformation into “abandoned files” in the newly constructed Israeli archives at the same time. The article proposes to relate to the ongoing looting of archives not merely as a violation of Palestinian property and rights, but rather as a continuous performance of national sovereignty. Sovereignty is performed as the continued project of partition of populations into distinct, differentiated groups, whereby violence among the two groups is both the pretext and the effect.
Let There Be Light: Wauja People and the Practice of Photographic Primitivism in Sebastião Salgado's Genesis
Authors: Ball Christopher
Published: May 2017

Sebastião Salgado's 2013 photographic book Genesis is analyzed as a work of primitivist realism. This analysis is based on ethnography of the photographer's encounter with Wauja people in Brazil in 2005 while he was taking photographs for the book. Primitivism has a long history in the production of images of indigenous subjects in anthropology, and it often projects through its images a narrative suggesting a separation between the modern and the premodern. The realist dimensions of photography reinscribe the spatiotemporal divide, whereas the artistic dimensions of Salgado's black‐and‐white images of indigenous people featured in Genesis suggest romantic nostalgia.
Survival of Staphylococcus pseudintermedius in modified Romanowsky staining solutions
Authors: Misan Angus , Chan Wei Yee , Trott Darren , Hill Peter B.
Published: May 2017

Background

Stains that are used regularly for patient‐side diagnosis to rapidly identify bacterial and fungal infections could become contaminated by common pathogens, such as Staphylococcus pseudintermedius, during slide immersion.

Hypothesis/Objectives

To determine whether the inoculation of S. pseudintermedius into modified Romanowsky type stains (Quick Dip®) results in viable bacterial contamination and whether this is influenced by the addition of organic debris (canine hair and skin).

Methods

A clinical isolate of S. pseudintermedius was inoculated into clean and organically contaminated Quick Dip® solutions (methanol fixative, eosin, methylene blue), and positive (broth) and negative (bleach) controls. Each solution was tested for the presence of viable bacteria by counting the number of colony forming units (CFU/mL) at various time points. Solutions also were examined under high power microscopy to count the number of visible bacteria at each time point.

Results

Staphylococcus pseudintermedius was able to survive in the clean and contaminated Quick Dip® stains for at least one hour, but by 24 h no viable bacteria remained. Survival of the bacteria was not supported in the fixative at any time point. Staphylococcus pseudintermedius remained visible under high power microscopy for up to 2 weeks in all organically contaminated solutions of the Quick Dip® set.

Conclusions and clinical importance

Staphylococcus pseudintermedius only remains viable in eosin and methylene blue for short periods of time, but the prolonged visibility of dead organisms could theoretically lead to the misdiagnosis of cytology samples.
Temperatures in Grinding—A Review
Authors: Brian Rowe W.
Published: May 2017

Many scientists contributed to the analysis of temperatures in grinding leading up to present-day understanding. This paper draws together important developments from various papers and aims to identify an improved general approach to thermal analysis with wide applicability including for conventional fine grinding, creep feed grinding, and high efficiency deep grinding. Complexity of the basic derivation is avoided since the resulting temperature model is based purely on heat balance. Challenges for future thermal analysis are indicated. Emphasis is placed on fundamental principles for improved accuracy and for convenience of application in process control.
Tool Accessibility Analysis for Robotic Drilling and Fastening
Authors: Dakdouk David , Xi Fengfeng
Published: May 2017

Robotic applications in aerospace manufacturing and aircraft assembly today are limited. This is because most of the aircraft parts are relatively crowded and have complex shapes that make tasks like robotic drilling and fastening more challenging. These challenges include tool accessibility, path, and motion planning. In this paper, a process methodology was developed to overcome the tool accessibility challenges facing robotic drilling and riveting for aircraft parts that are located in crowded work environments. First, the tool accessibility was analyzed based on the global accessibility area (GAA) and the global accessibility volume (GAV) to determine the accessible boundaries for parts with zero, one, and two surfaces curvatures. Then, the path for the tool was generated while taking in consideration the approachability planning. This approach generates a number of intermediate points that enable the tool to maneuver around obstacles to reach the final target points if they are accessible. Last, a software application was developed to simulate the drilling and riveting tasks, and to validate the proposed process. The results of the simulation confirmed the proposed methodology and provided a numerical feedback describing the level of crowdedness of the work environment. The accessibility percentage can then be used by the design team to reduce the design complexity and increase the level of tool accessibility.
Size Distribution Estimation of Three-Dimensional Particle Clusters in Metal-Matrix Nanocomposites Considering Sampling Bias
Authors: Wu Jianguo , Yuan Yuan , Li Xiaochun
Published: May 2017

Nanoparticle clustering phenomenon is a critical quality issue in metal-matrix nanocomposites (MMNCs) manufacturing. Accurate estimation of the 3D cluster size distribution based on the 2D cross section images is essential for quality assessment, quality control, and process optimization. The existing studies often draw conclusions with observable samples, which are inherently biased because large clusters are more likely to be intersected by scanning electron microscope (SEM) images compared with small ones. This paper takes into account this sampling bias and proposes two statistical approaches, namely, the maximum likelihood estimation (MLE) and the method of moments (MM), to estimate the distribution parameters accurately. Numerical studies and real case study demonstrate the effectiveness and accuracy of the proposed approaches.
A Simulation Study on the Dynamic Stability of a Fluid-Conveying Pipe With a Constant Velocity Leakage
Authors: Meng Shuai , Li Ye , Wang Xuefeng
Published: May 2017

Motivated by the fact that a leaking pipe can lose or gain energy from the leaking flow, this study attempts to explore the nonconservative leaking flow effect on the dynamic stability of a simply supported pipe with a constant velocity leakage. It employs a two-dimensional nonlinear longitudinal and lateral coupling model, and the leakage effect is accounted for by virtual work due to virtual momentum transport at the leaking point. The equations of motion are solved by Galerkin-based multimode approach and the Houbolt's finite difference time integration. It demonstrates that when there is a leaking flow, a stable pipe can be refined or destabilized via a static pitchfork bifurcation, and a buckling pipe can be stabilized or deteriorated into a worse divergence condition. The critical leaking flow velocities and the excited buckling modes depend on the leaking fluid mass and the leak's position. This study may provide some insights to assist the leak detection system (LDS) of a pipe transporting high-pressure oil or gas in modern engineering.
Inkjet printing of liquid-exfoliated, highly conducting graphene/poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) nanosheets for organic electronics
Authors: Desai Jay A. , Biswas Chandan , Kaul Anupama B.
Published: May 2017

In this work, highly dispersive graphene inks are demonstrated by liquid-phase exfoliation of the bulk graphite crystal in the solvent N-methyl-2-pyrrolidone (NMP). In order to make the inks suitable for inkjet printing, an avenue to tailor the viscosity of the NMP-based ink has been developed through the addition of the organic additive poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The use of PEDOT:PSS with graphene inks shows the solutions to exhibit high dispersion densities as deciphered through optical absorbance measurements, while the inkjet printed structures themselves show a uniform microstructure and typical resistivity values of approximately 0.26 mΩ m on average with graphene/PEDOT:PSS inks and can be improved further with the modification of ink properties. PEDOT:PSS as a conductive surfactant enhances the electrical conductivity of graphene patterns, and a viscosity of about 12 cP which is ideal for inkjet printing can be achieved by adding a very small amount (0.25 wt. %) of PEDOT:PSS to NMP as compared to higher amounts of nonconductive surfactants like ethyl cellulose needed to obtain similar levels of viscosity. PEDOT:PSS is a workhorse of the organic electronics industry, and this work on graphene/PEDOT:PSS composite inks provides new directions to the organic electronics industry to incorporate two-dimensional layered materials in device platforms.
Approximate solutions to acoustic scattering from a ribbed finite plate
Authors: Tran-Van-Nhieu Michel , Maze Gérard , Décultot Dominique
Published: May 2017

Acoustic scattering from a finite plate reinforced by parallel ribs with arbitrary rib spacing is investigated by applying thin plate and beam theories. The modal component of the surface pressure is calculated by an asymptotic expression that is only valid for higher-order modes at high frequencies. An approximate expression is derived for the far field scattered pressure by inverting matrices the rank of which is equal to twice the number of ribs. When the ribs are regularly spaced, approximate analytical expressions are proposed to calculate Bragg and forward Bloch–Floquet waves scattering separately from backward Bloch–Floquet waves scattering. These solutions are useful to deal with scattering problems where flexural waves are strongly attenuated after reflection on the edges of the plate. Finally the relevancy of the approximate expressions is evaluated by comparing numerical simulations to experimental data.
Analysis of Spanish consonant recognition in 8-talker babble
Authors: Moreno-Torres Ignacio , Otero Pablo , Luna-Ramírez Salvador , Garayzábal Heinze Elena
Published: May 2017

This paper presents the results of a closed-set recognition task for 80 Spanish consonant-vowel sounds (16 C × 5 V, spoken by 2 talkers) in 8-talker babble (–6, –2, +2 dB). A ranking of resistance to noise was obtained using the signal detection d′ measure, and confusion patterns were analyzed using a graphical method (confusion graphs). The resulting ranking indicated the existence of three resistance groups: (1) high resistance: /ʧ, s, ʝ/; (2) mid resistance: /r, l, m, n/; and (3) low resistance: /t, θ, x, ɡ, b, d, k, f, p/. Confusions involved mostly place of articulation and voicing errors, and occurred especially among consonants in the same resistance group. Three perceptual confusion groups were identified: the three low-energy fricatives (i.e., /f, θ, x/), the six stops (i.e., /p, t, k, b, d, ɡ/), and three consonants with clear formant structure (i.e., /m, n, l/). The factors underlying consonant resistance and confusion patterns are discussed. The results are compared with data from other languages.
Microphone array geometry optimization for traffic noise analysis
Authors: Bjelić Miloš , Stanojević Miodrag , Šumarac Pavlović Dragana , Mijić Miomir
Published: May 2017

This paper outlines an approach for obtaining microphone array geometry for use in traffic noise analysis. The designed array has a smaller number of microphones compared to existing solutions, thereby reducing the cost of system realization. The array geometry is irregular, consists of 24 microphones, and was obtained by an optimization procedure that minimizes beampatterns sidelobes. Microphone position optimization was performed in the frequency band from 300 Hz to 2000 Hz, defined by traffic noise characteristics. The designed array is used in ongoing research dedicated to the analysis of angular distribution of incident traffic noise sound energy impeding a facade in urban environment.
A jamming-like mechanism of yield-stress increase caused by addition of nonmagnetizable particles to magnetorheological suspensions
Authors: Wilson Benjamin T. , Klingenberg Daniel J.
Published: May 2017

Particle-level simulations are employed to investigate the mechanism by which nonmagnetizable particles enhance the field-induced shear stress in magnetorheological fluids. Large amplitude oscillatory shear reveals that nonmagnetizable spheres increase the suspension stiffness; the transition to nonlinear deformation remains unaffected suggesting that the nonmagnetizable spheres do not alter the stability of the clusters of magnetizable spheres. Snapshots reveal that nonmagnetizable spheres participate in stress transfer via repulsive-force clusters in a mechanism similar to jamming in hard-sphere suspensions. Partial stresses, number of repulsive-force clusters, and transient rheological behavior further support that nonmagnetizable spheres directly enhance the stress via repulsive-force clusters. The repulsive-force clusters contain both magnetizable and nonmagnetizable spheres, which likely explains the observation that nonmagnetizable spheres enhance the magnetic field-induced stress, even though they are not magnetizable.
The ground truth about metadata and community detection in networks
Authors: Peel Leto , Larremore Daniel B. , Clauset Aaron
Published: May 2017

Troubles with community detection in networks: No ground truth, no free lunch, and the complex coupling of metadata with structure.
High-predation habitats affect the social dynamics of collective exploration in a shoaling fish
Authors: Ioannou Christos C. , Ramnarine Indar W. , Torney Colin J.
Published: May 2017

Comparing across populations, we show that predation has multiple effects on collective exploration in groups of guppies.
Resilience offers escape from trapped thinking on poverty alleviation
Authors: Lade Steven J. , Haider L. Jamila , Engström Gustav , Schlüter Maja
Published: May 2017

The complex roles of nature and culture in poverty traps call for diverse and often transformative poverty alleviation strategies.
Mauritius invites primate research labs to set up shop
Authors: Wadman Meredith
Published: May 2017

Animal welfare activists protest move by nation that exports research macaques
NASA pushes for diversity in planetary science
Authors: Voosen Paul
Published: May 2017

New Frontiers mission announcement includes call for more inclusive teams
Fast and curious
Authors: Clery Daniel
Published: May 2017

A global robotic telescope network helps astronomers keep up with the
fast-changing sky
Advances in engineering hydrogels
Authors: Zhang Yu Shrike , Khademhosseini Ali
Published: May 2017

Wet, soft, squishy, and tunable

Hydrogels are highly cross-linked polymer networks that are heavily swollen with water. Hydrogels have been used as dynamic, tunable, degradable materials for growing cells and tissues. Zhang and Khademhosseini review the advances in making hydrogels with improved mechanical strength and greater flexibility for use in a wide range of applications.

Science
, this issue p.
eaaf3627
Branch-specific plasticity of a bifunctional dopamine circuit encodes protein hunger
Authors: Liu Qili , Tabuchi Masashi , Liu Sha , Kodama Lay , Horiuchi Wakako , Daniels Jay , Chiu Lucinda , Baldoni Daniel , Wu Mark N.
Published: May 2017

The drive to eat protein is mediated by plastic changes in a dedicated neuronal circuit in
Drosophila
.
Beyond Hamilton's rule
Authors: de Vladar Harold P. , Szathmáry Eörs
Published: May 2017

A broader view of how relatedness affects the evolution of altruism is emerging
Thomas Earl Starzl (1926–2017)
Authors: Fung John J.
Published: May 2017

Father of modern transplantation
Identification of Protective B-Cell Epitopes within the Novel Malaria Vaccine Candidate Plasmodium falciparum Schizont Egress Antigen 1
Authors: Nixon Christina E. , Park Sangshin , Pond-Tor Sunthorn , Raj Dipak , Lambert Lynn E. , Orr-Gonzalez Sachy , Barnafo Emma K. , Rausch Kelly M. , Friedman Jennifer F. , Fried Michal , Duffy Patrick E. , Kurtis Jonathan D.
Published: May 2017

Naturally acquired antibodies to
Plasmodium falciparum
schizont egress antigen 1 (PfSEA-1A) are associated with protection against severe malaria in children. Vaccination of mice with SEA-1A from
Plasmodium berghei
(PbSEA-1A) decreases parasitemia and prolongs survival following
P. berghei
ANKA challenge. To enhance the immunogenicity of PfSEA-1A, we identified five linear B-cell epitopes using peptide microarrays probed with antisera from nonhuman primates vaccinated with recombinant PfSEA-1A (rPfSEA-1A). We evaluated the relationship between epitope-specific antibody levels and protection from parasitemia in a longitudinal treatment-reinfection cohort in western Kenya. Antibodies to three epitopes were associated with 16 to 17% decreased parasitemia over an 18-week high transmission season. We are currently designing immunogens to enhance antibody responses to these three epitopes.
Evaluation of Sensitivity and Specificity Performance of Elecsys HTLV-I/II Assay in a Multicenter Study in Europe and Japan
Authors: Laperche Syria , Sauleda Silvia , Piron Maria , Mühlbacher Annelies , Schennach Harald , Schottstedt Volkmar , Queirós Lucinda , Uno Naoki , Yanagihara Katsunori , Imdahl Roland , Hey Ariann , Klinkicht Markus , Melchior Walter , Muench Peter , Watanabe Toshiki
Published: May 2017

Screening of blood for human T-cell lymphotropic virus type 1 and type 2 (HTLV-1 and -2, respectively) is important to diagnose and prevent infection and ensure the safety of blood supplies. The Elecsys HTLV-I/II assay is a newly developed, electrochemiluminescence screening assay for the detection of HTLV-1/2 infection. The sensitivity and specificity of the Elecsys HTLV-I/II assay were determined using well-characterized HTLV-1/2-positive serum and plasma samples and routine diagnostic and blood donor samples expected to be HTLV negative, respectively. These results were compared with those for at least one of the following CE-marked assays at seven independent laboratories and the Roche Diagnostics facility in Penzberg, Germany: Abbott Architect rHTLV-I/II, Ortho Avioq HTLV-I/II Microelisa system, Abbott Prism HTLV-I/HTLV-II, and DiaSorin Murex HTLV I+II. Fujirebio INNO-LIA HTLV-I/II Score was used as a confirmatory assay. The Elecsys HTLV-I/II, Abbott Architect rHTLV-I/II, and Abbott Prism HTLV-I/HTLV-II assays detected all HTLV-1/2-positive samples (sensitivity, 100%). Sensitivity for Ortho Avioq HTLV-I/II was 98.63%. The Elecsys HTLV-I/II assay had a specificity of 99.95% in blood donor samples, which was comparable to results for the other assays (range, 99.91 to 100%). In routine diagnostic samples, the specificity of the Elecsys HTLV-I/II assay was 99.83%, compared with 99.70% for Abbott Architect rHTLV-I/II. Specificity for the Elecsys HTLV-I/II assay in potentially cross-reactive samples was 100%, compared with 99.0% for Ortho Avioq HTLV-I/II and 99.2% for DiaSorin Murex HTLV I+II. The Elecsys HTLV-I/II assay has the sensitivity and specificity to support its use as a routine screening assay for detecting HTLV infection.
Isolation of Campylobacter Species from Stool Samples by Use of a Filtration Method: Assessment from a United States-Based Population
Authors: Nachamkin Irving , Nguyen Phi
Published: May 2017

Fecal samples submitted to our clinical microbiology laboratory from patients in the Philadelphia region were prospectively analyzed for
Campylobacter
species other than
C. jejuni
and
C. coli
using a filtration method and microaerobic conditions with increased H
2
concentrations. Of 225 samples tested, 13 (5.8%) yielded
Campylobacter
species, with frequent isolation of
C. concisus
. The majority of
Campylobacter
species were not clinically significant. Additional studies in U.S. populations are warranted.
Regulation of Tacaribe Mammarenavirus Translation: Positive 5′ and Negative 3′ Elements and Role of Key Cellular Factors
Authors: Foscaldi Sabrina , D'Antuono Alejandra , Noval María Gabriela , de Prat Gay Gonzalo , Scolaro Luis , Lopez Nora
Published: May 2017

Mammarenaviruses are enveloped viruses with a bisegmented negative-stranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic mRNAs bearing a capped 5′ untranslated region (UTR) and lacking 3′ poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open reading frame and transcripts bearing modified 5′ and/or 3′ UTR were evaluated in a cell-based translation assay. We found that the presence of the cap structure at the 5′ end dramatically increases translation efficiency and that the viral 5′ UTR comprises stimulatory signals while the 3′ UTR,specifically the presence of a terminal C+G-rich sequence and/or a stem-loop structure, down-modulates translation. Additionally, translation was profoundly reduced in eukaryotic initiation factor (eIF) 4G-inactivated cells, whereas depletion of intracellular levels of eIF4E had less impact on virus-like mRNA translation than on a cell-like transcript. Translation efficiency was independent of NP expression or TCRV infection. Our results indicate that TCRV mRNAs are translated using a cap-dependent mechanism, whose efficiency relies on the interplay between stimulatory signals in the 5′ UTR and a negative modulatory element in the 3′ UTR. The low dependence on eIF4E suggests that viral mRNAs may engage yet-unknown noncanonical host factors for a cap-dependent initiation mechanism.

IMPORTANCE
Several members of the
Arenaviridae
family cause serious hemorrhagic fevers in humans. In the present report, we describe the mechanism by which Tacaribe virus, a prototypic nonpathogenic New World mammarenavirus, regulates viral mRNA translation. Our results highlight the impact of untranslated sequences and key host translation factors on this process. We propose a model that explains how viral mRNAs outcompete cellular mRNAs for the translation machinery. A better understanding of the mechanism of translation regulation of this virus can provide the bases for the rational design of new antiviral tools directed to pathogenic arenaviruses.
Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus
Authors: Sobel Leonard Ashley , Weissman Daniel B. , Greenbaum Benjamin , Ghedin Elodie , Koelle Katia
Published: May 2017

The bottleneck governing infectious disease transmission describes the size of the pathogen population transferred from the donor to the recipient host. Accurate quantification of the bottleneck size is particularly important for rapidly evolving pathogens such as influenza virus, as narrow bottlenecks reduce the amount of transferred viral genetic diversity and, thus, may decrease the rate of viral adaptation. Previous studies have estimated bottleneck sizes governing viral transmission by using statistical analyses of variants identified in pathogen sequencing data. These analyses, however, did not account for variant calling thresholds and stochastic viral replication dynamics within recipient hosts. Because these factors can skew bottleneck size estimates, we introduce a new method for inferring bottleneck sizes that accounts for these factors. Through the use of a simulated data set, we first show that our method, based on beta-binomial sampling, accurately recovers transmission bottleneck sizes, whereas other methods fail to do so. We then apply our method to a data set of influenza A virus (IAV) infections for which viral deep-sequencing data from transmission pairs are available. We find that the IAV transmission bottleneck size estimates in this study are highly variable across transmission pairs, while the mean bottleneck size of 196 virions is consistent with a previous estimate for this data set. Furthermore, regression analysis shows a positive association between estimated bottleneck size and donor infection severity, as measured by temperature. These results support findings from experimental transmission studies showing that bottleneck sizes across transmission events can be variable and influenced in part by epidemiological factors.

IMPORTANCE
The transmission bottleneck size describes the size of the pathogen population transferred from the donor to the recipient host and may affect the rate of pathogen adaptation within host populations. Recent advances in sequencing technology have enabled bottleneck size estimation from pathogen genetic data, although there is not yet a consistency in the statistical methods used. Here, we introduce a new approach to infer the bottleneck size that accounts for variant identification protocols and noise during pathogen replication. We show that failing to account for these factors leads to an underestimation of bottleneck sizes. We apply this method to an existing data set of human influenza virus infections, showing that transmission is governed by a loose, but highly variable, transmission bottleneck whose size is positively associated with the severity of infection of the donor. Beyond advancing our understanding of influenza virus transmission, we hope that this work will provide a standardized statistical approach for bottleneck size estimation for viral pathogens.
Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein
Authors: Leemans A. , De Schryver M. , Van der Gucht W. , Heykers A. , Pintelon I. , Hotard A. L. , Moore M. L. , Melero J. A. , McLellan J. S. , Graham B. S. , Broadbent L. , Power U. F. , Caljon G. , Cos P. , Maes L. , Delputte P.
Published: May 2017

Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs
in vivo
and how this might impact RSV replication.

IMPORTANCE
Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are able to protect infants from severe disease, if administered prophylactically. However, antibody responses established after natural RSV infections are poorly protective against reinfection, and high levels of antibodies do not always correlate with protection. Therefore, RSV might be capable of interfering, at least partially, with antibody-induced neutralization. In this study, a process through which surface-expressed RSV F proteins are internalized after interaction with RSV-specific antibodies is described. One the one hand, this antigen-antibody complex internalization could result in an antiviral effect, since it may interfere with virus particle formation and virus production. On the other hand, this mechanism may also reduce the efficacy of antibody-mediated effector mechanisms toward infected cells.
Antibody Preparations from Human Transchromosomic Cows Exhibit Prophylactic and Therapeutic Efficacy against Venezuelan Equine Encephalitis Virus
Authors: Gardner Christina L. , Sun Chengqun , Luke Thomas , Raviprakash Kanakatte , Wu Hua , Jiao Jin-an , Sullivan Eddie , Reed Douglas S. , Ryman Kate D. , Klimstra William B.
Published: May 2017

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus that causes low mortality but high morbidity rates in humans. In addition to natural outbreaks, there is the potential for exposure to VEEV via aerosolized virus particles. There are currently no FDA-licensed vaccines or antiviral therapies for VEEV. Passive immunotherapy is an approved method used to protect individuals against several pathogens and toxins. Human polyclonal antibodies (PAbs) are ideal, but this is dependent upon serum from convalescent human donors, which is in limited supply. Non-human-derived PAbs can have serious immunoreactivity complications, and when “humanized,” these antibodies may exhibit reduced neutralization efficiency. To address these issues, transchromosomic (Tc) bovines have been created, which can produce potent neutralizing human antibodies in response to hyperimmunization. In these studies, we have immunized these bovines with different VEEV immunogens and evaluated the protective efficacy of purified preparations of the resultant human polyclonal antisera against low- and high-dose VEEV challenges. These studies demonstrate that prophylactic or therapeutic administration of the polyclonal antibody preparations (TcPAbs) can protect mice against lethal subcutaneous or aerosol challenge with VEEV. Furthermore, significant protection against unrelated coinfecting viral pathogens can be conferred by combining individual virus-specific TcPAb preparations.

IMPORTANCE
With the globalization and spread or potential aerosol release of emerging infectious diseases, it will be critical to develop platforms that are able to produce therapeutics in a short time frame. By using a transchromosomic (Tc) bovine platform, it is theoretically possible to produce antigen-specific highly neutralizing therapeutic polyclonal human antibody (TcPAb) preparations in 6 months or less. In this study, we demonstrate that Tc bovine-derived Venezuelan equine encephalitis virus (VEEV)-specific TcPAbs are highly effective against VEEV infection that mimics not only the natural route of infection but also infection via aerosol exposure. Additionally, we show that combinatorial TcPAb preparations can be used to treat coinfections with divergent pathogens, demonstrating that the Tc bovine platform could be beneficial in areas where multiple infectious diseases occur contemporaneously or in the case of multipathogen release.
Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection
Authors: Cui Liang , Hou Jue , Fang Jinling , Lee Yie Hou , Costa Vivian Vasconcelos , Wong Lan Hiong , Chen Qingfeng , Ooi Eng Eong , Tannenbaum Steven R. , Chen Jianzhu , Ong Choon Nam
Published: May 2017

Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend—most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.

IMPORTANCE
Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly increased the challenges in the study of dengue pathogenesis and the development of therapeutics. Metabolomics provides global views of small-molecule metabolites and is a useful tool for finding metabolic pathways related to disease processes. Here, we conducted a serum metabolomics study on a model using humanized mice with dengue infection that had significant levels of human platelets, monocytes/macrophages, and hepatocytes. Forty-eight differential metabolites were identified, and the underlying perturbed metabolic pathways are quite similar to the pathways found to be altered in dengue patients in previous metabolomics studies, indicating that humanized mice could be a highly relevant small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.
Novel β-Lactamase
bla
ARL
in Staphylococcus arlettae
Authors: Andreis Sabrina N. , Perreten Vincent , Schwendener Sybille
Published: May 2017

Penicillins are an important group of antibiotics used to treat various types of infections caused by Gram-positive bacteria. So far, the
blaZ
gene was the only known β-lactamase gene in staphylococci. However, other putative β-lactamases were identified, and one of them was shown to be a novel functional β-lactamase encoded by
bla
ARL
in
Staphylococcus arlettae
, further limiting treatment options.
Knotted urethral catheter: a twist in the tail
Authors: Jehangir Susan , David Dennis Darren
Published: May 2017

Inadvertent knotting of infant feeding tubes used for clean intermittent catheterisation (CIC) is a rare complication in paediatric patients. The small flexible tubes used in infants if advanced too far into the bladder may form a knot as the bladder empties. Surgical intervention is required especially if it is lodged in the urethra. We present a case of a baby boy aged 4 months on CIC with a 6 Fr feeding tube, which required a meatotomy for removal. Education while instituting CIC must emphasise the length of catheter insertion, the chance of knotted catheter and steps to take if it occurs. A dedicated urotherapy nurse would be ideal.
Cardioversion of a supraventricular tachycardia (SVT) in a 7-year-old using a postural modification of the Valsalva manoeuvre
Authors: Morley-Smith Edward John , Gagg James , Appelboam Andrew
Published: May 2017

A boy aged 7 years presented with his parents to the emergency department (ED). He had a known diagnosis of paroxysmal supraventricular tachycardia (SVT) and was under the care of paediatricians. He had been suffering episodes of palpitations and chest pain for over a year and had been prescribed atenolol 25 mg ON, though the side effects meant he had not taken it for a month prior to presentation. He had 2 previous confirmed episodes of SVT, one that reverted with Valsalva manoeuvres, and the other with intravenous adenosine. In the ED, an ECG was recorded showing SVT at 180 bpm. Aside from his tachycardia, he was haemodynamically stable. The postural modification of the Valsalva technique was performed within 5 min of arrival, with reversion to sinus rhythm occurring during the leg-lift phase on the first attempt. After 30 min of observation, the child remained stable and was discharged home.
ERG and OCT findings of a patient with a clinical diagnosis of occult macular dystrophy in a patient of Ashkenazi Jewish descent associated with a novel mutation in the gene encoding RP1L1
Authors: Saffra Norman , Seidman Carly Jane , Rakhamimov Aleksandr , Tsang Stephen H
Published: May 2017

A 57-year-old man with a past medical history of diabetes presented for consultation with a several year history of slowly progressive vision loss in both eyes, which continued to deteriorate over 7 years of follow-up. Multimodal imaging was performed and was significant for the following: on spectral domain optical coherence tomography, a gap lesion was present in the ellipsoid layer, beneath the umbo, as well as subtle macular changes on auto fluorescence imaging. Multifocal electroretinography was performed and was abnormal, and a clinical diagnosis of occult macular dystrophy was made. The patient was subsequently evaluated with genetic testing that revealed a novel p.P73S:c 217C>T nonsense mutation within the retinitis pigmentosa 1-like-1 (RP1L1) gene. The clinical significance of the identified variation will require further investigation.
Pasteurella multocidameningoencephalitis in an immunocompetent adult with multiple cat scratches
Authors: Clarke David Alistair , Mcbride Angela , Kelsey Michael , Killingley Ben
Published: May 2017

We present the case of a 49-year-old woman admitted to our Acute Medical Unit with a 2-day history of fever, vomiting and confusion. The patient was alcohol dependent and had sustained several scratches from her pet cat, which her pet dog had licked. She deteriorated in the Emergency Department—developing high fever, worsening confusion and meningism. Blood cultures were taken and broad spectrum antibiotics commenced prior to CT scanning and diagnostic lumbar puncture. Blood cultures and CSF 16S ribosomal PCR confirmed a diagnosis ofPasteurella multocidabacteraemia and meningoencephalitis. The patient was successfully treated with 14 days of intravenous antibiotics.P multocidais a Gram-negative coccobacillus which frequently colonises the nasopharynx of animals; it is a recognised but very rare cause of meningoencephalitis in immunocompetent adults. This case highlights the need to considerP multocidainfection in patients with prior animal contact, regardless of their immune status.
Antacid abuse: a rare cause of severe hypercalcaemia
Authors: Stoney Ben , Bagchi Gautam
Published: May 2017

We discuss a case of an 81-year-old man who presented to hospital with a case of severe hypercalcaemia (5.07 mmol/L). The two most common causes of hypercalcaemia, making up around 90% of the cases, are malignancy and primary hyperparathyroidism. Initial investigations are guided by this knowledge. In this case, no underlying malignancy or evidence of a parathyroid adenoma causing primary hyperparathyroidism was found. Instead, on further history, it was found that this patient had troublesome dyspepsia symptoms for which he had ingested 10–12 calcium carbonate tablets a day for the preceding 2 years. This amounts to 6.6–7.9 g of calcium carbonate per day compared with the guideline daily intake of calcium of 1 g. His presentation of severe hypercalcaemia was therefore diagnosed as milk-alkali syndrome secondary to calcium carbonate tablet abuse.
Can alternating temperature, moist chilling, and gibberellin interchangeably promote the completion of germination in Clematis vitalba seeds?
Authors: Picciau Rosangela , Porceddu Marco , Bacchetta Gianluigi
Published: May 2017

Each plant species has particular requirements for seed germination, and some of them respond differently to constant or alternating temperature regimes. In this study, the interchangeable effects of different treatments and temperatures on the completion of seed germination of Clematis vitalba L. were investigated. The seeds were tested with a constant (from 5 °C to 25 °C) or a fluctuating (25/10 °C) temperature regime, and the effect of gibberellic acid (GA3), incubation at warm (W) or cold (C) temperatures while being imbibed, and drying after ripening (DAR) were evaluated. The final germination percentages and the time in days required to reach 50% of germination (T50) were calculated. GA3 and C significantly enhanced completion of seed germination at all of the temperatures tested. A strong positive effect of alternating temperature was observed, which triggered completion of seed germination regardless of treatment. Under the fluctuating temperature, the chilled seeds had the most rapid germination. Low germination rates were observed for both control and DAR treatments. Seeds of C. vitalba display a certain degree of dormancy, which can be broken by moist chilling and GA3 treatments. Moreover, alternating temperature stimulates the completion of seed germination by satisfying certain physiological requirements for germination under constant temperatures.
Evidence of necroptosis in hearts subjected to various forms of ischemic insults
Authors: Adameova Adriana , Hrdlicka Jaroslav , Szobi Adrian , Farkasova Veronika , Kopaskova Katarina , Murarikova Martina , Neckar Jan , Kolar Frantisek , Ravingerova Tatiana , Dhalla Naranjan S.
Published: May 2017

Long-lasting ischemia can result in cell loss; however, repeated episodes of brief ischemia increase the resistance of the heart against deleterious effects of subsequent prolonged ischemic insult and promote cell survival. Traditionally, it is believed that the supply of blood to the ischemic heart is associated with release of cytokines, activation of inflammatory response, and induction of necrotic cell death. In the past few years, this paradigm of passive necrosis as an uncontrolled cell death has been re-examined and the existence of a strictly regulated form of necrotic cell death, necroptosis, has been documented. This controlled cell death modality, resembling all morphological features of necrosis, has been investigated in different types of ischemia-associated heart injuries. The process of necroptosis has been found to be dependent on the activation of RIP1–RIP3–MLKL axis, which induces changes leading to the rupture of cell membrane. This pathway is activated by TNF-α, which has also been implicated in the cardioprotective signaling pathway of ischemic preconditioning. Thus, this review is intended to describe the TNF-α-mediated signaling leading to either cell survival or necroptotic cell death. In addition, some experimental data suggesting a link between heart dysfunction and the cellular loss due to necroptosis are discussed in various conditions of myocardial ischemia.