bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal sepsis and simple minor neurological dysfunction
Authors: Kavas Nazan , Arısoy Ayşe Engin , Bayhan Asuman , Kara Bülent , Günlemez Ayla , Türker Gülcan , Oruç Meral , Gökalp Ayşe Sevim
Published: December 2016

Background

This study examined potential risk factors for and consequences of simple minor neurological dysfunction (SMND), in a group of very low‐birthweight newborns followed until preschool age.

Methods

This was a prospective longitudinal study. Children with birthweight <1500 g were assessed at 4–6 years of age. Twenty‐eight children with normal neurological examination and 35 children with SMND were included in the final analysis. Risk factors for the development of SMND and its association with certain neuropsychiatric conditions were studied.

Results

Based on neonatal data, in children with SMND, Apgar score at 1 min (6.13 ± 2.37 vs 7.66 ± 1.04, P = 0.008) and at 5 min (8.63 ± 1.29 vs 9.45 ± 0.65, P = 0.019) was lower, duration of hospital stay was longer (45.8 ± 21.8 vs 35.1 ± 18.2 days, P = 0.037), and the frequency of sepsis was higher (73.5 vs 25%, P < 0.001). Sepsis was found to be an independent risk factor for SMND (OR, 7.6; 95% CI: 2.2–26.0; P = 0.001). The children with SMND had lower intelligence quotient and higher prevalence of hyperactivity and refraction error.

Conclusion

Postnatal sepsis was the single most important risk factor for the development of SMND, and these children with SMND are at great risk for certain neuropsychiatric conditions. Preventive strategies, particularly for sepsis in the neonatal period, and early diagnosis and rehabilitation of future neuropsychiatric disorders are needed for better management of these cases.
Revenue Management of Reusable Resources with Advanced Reservations
Authors: Chen Yiwei , Levi Retsef , Shi Cong
Published: December 2016

We consider a revenue management problem wherein the seller is endowed with a single type resource with a finite capacity and the resource can be repeatedly used to serve customers. There are multiple classes of customers arriving according to a multi‐class Poisson process. Each customer, upon arrival, submits a service request that specifies his service start time and end time. Our model allows customer advanced reservation times and services times in each class to be arbitrarily distributed and correlated. Upon arrival of each customer, the seller must instantaneously decide whether to accept this customer's service request. A customer whose request is denied leaves the system. A customer whose request is accepted is allocated with a specific item of the resource at his service start time. The resource unit occupied by a customer becomes available to other customers after serving this customer. The seller aims to design an admission control policy that maximizes her expected long‐run average revenue. We propose a policy called the ε‐ perturbation class selection policy ( ε‐CSP), based on the optimal solution in the fluid setting wherein customers are infinitesimal and customer arrival processes are deterministic, under the restriction that the seller can utilize at most (1 −  ε) of her capacity for any ε ∈ (0, 1). We prove that the ε‐CSP is near‐optimal. More precisely, we develop an upper bound of the performance loss of the ε‐CSP relative to the seller's optimal revenue, and show that it converges to zero with a square‐root convergence rate in the asymptotic regime wherein the arrival rates and the capacity grow up proportionally and the capacity buffer level ε decays to zero.
Supply Chain Models with Mutual Commitments and Implications for Social Responsibility
Authors: Chen Jiguang , Hu Qiying , Song Jing‐Sheng
Published: December 2016

In today's increasingly globalized environment, more and more companies recognize the mutual dependence of supply chain partners in value creation. When making business decisions, they take into consideration their partners’ bottom line profitability, especially in emerging markets. The question is, is this kind of practice sustainable? This study makes an attempt to formalize this issue by examining a stylized two‐party supply chain model in which each player maximizes its own profit while making a certain commitment to its partner. We compare five different games between the two supply‐chain partners, which reflect different power positions of the players and different levels of commitment. We identify conditions under which both players are better off with mutual commitments than without, a situation we call win–win. We show that win–win can be achieved if and only if the mutual commitments are comparable. Thus, the recognition of mutual dependence of the supply chain members needs to be translated into reciprocal concerns. In addition, different players’ commitments play different roles but together they have a similar effect as a profit sharing contract. Finally, we discuss the implications of our findings in the context of socially responsible operations. In particular, our analyses show that it is possible to care about the supply chain partners’ bottom line without sacrificing one's own profitability, and our models can be used as a tool to determine the commitment levels by evaluating the predicted outcome.
Pathogenicity of isolates ofMagnaporthespp. from wheat and grasses infecting seedlings and mature wheat plants in Argentina
Authors: Perelló A. E. , Martinez I. , Sanabria A. , Altamirano R. , Sibole J. V.
Published: December 2016

Wheat blast of wheat (Triticum aestivum), caused byMagnaporthe oryzaepathotypetriticum(MoT; anamorphPyricularia oryzae) is a destructive disease in the South American countries of Brazil, Paraguay and Bolivia. In Argentina, the fungus was recently recorded on wheat and barley plants in the northeast part of the country, Buenos Aires and Corrientes Provinces, with a potential for spreading. This work aimed to study, for the first time, the morphocultural and pathogenic characteristics ofMagnaportheisolates collected from wheat and other herbaceous species in Argentina and three neighbouring countries (Paraguay, Brazil and Bolivia) and determine their aggressiveness on wheat varieties. Statistical differences among isolates, culture media, and development conditions were found for conidia colour, growth rate, size and sporulation rate. Pathogenicity tests performed on seedlings with 19 isolates ofMagnaporthespp. under greenhouse conditions showed a maximum disease severity of 55.3% and 66.7% for varietiesBIOINTA3004 and Baguette 18, respectively. Weed and grass isolates were infectious on wheat, demonstrating their potential epidemiological role on the disease. Spike disease severity was 34.6% for the host × pathogen interaction ofBIOINTA3004 × PY22. Observed symptoms included partial or total spike bleaching, and glume and rachis discolouration. The 1000‐grain weight was significantly reduced to 38.5% and 63.1% for cultivarsBIOINTA3004 and Baguette 18, respectively. The disease affected grain germination, which fell to 65.9% for seeds infected with thePYAR22 isolate. Symptoms observed in infected grains were partial spotting, grain softening, and rot symptoms with the presence of a greyish mould.
Perceptions of the influence of social media and therapeutic relationships on nurses: a systematic review protocol of qualitative evidence
Authors: Griffis Leigh , Falder-Saeed Karie
Published: December 2016

Review question/objective:

The objective of the review is to explore the perceptions of the influence social media has on professional boundaries and therapeutic relationships between nurses and their patients and families.
Effectiveness of caregiver-provided cognitive interventions on cognition, social functioning and quality of life among older adults with major neurocognitive disorder: a systematic review protocol
Authors: Silva Rosa , Cardoso Daniela , Abrunheiro Sérgio , Almeida Maria , Apóstolo João
Published: December 2016

Review question/objective:

The objective of this systematic review is to synthesize the best available evidence on the effectiveness of individual cognitive interventions (CIs) provided by caregivers on cognition, social functioning and quality of life among older adults (≥65 years) with major neurocognitive disorder (NCD).

The review questions are as follows:

What is the best available evidence on the effectiveness of individual CIs provided by caregivers on cognitive domains such as memory, problem-solving and verbal fluency among older adults (≥65 years) with major NCD?

What is the best available evidence regarding the effectiveness of individual CIs provided by caregivers on the social functioning and quality of life among older adults (≥65 years) with major NCD?
Effect of Hybridizing and Optimization of TiC on the Tribological Behavior of Mg–MoS2 Composites
Authors: Narayanasamy P. , Selvakumar N.
Published: December 2016

In the present study, the effects of TiC content on the microstructure, hardness, and wear property are to be investigated. Magnesium matrix hybrid composites reinforced with varying wt.% of TiC (0, 5, 10, 15, and 20) and a fixed wt.% of MoS2 (7.5) were produced by powder metallurgy. The microstructure of the hybrid composite samples was analyzed using optical microscopy. Elemental composition of sintered specimens was determined by energy dispersive X-ray spectroscopy (EDS) analysis. The Vicker's hardness test was performed in different locations on the sintered specimen surface with a load of 5 g and 15 s dwell time. The dry sliding wear test was carried out in a pin-on-disk wear testing machine at various load (5–30 N), velocity (0.5–3 m/s), and sliding distance (500–3000 m). Tribological investigation was statistically analyzed using Taguchi L27 orthogonal array with four factors at three levels. A graphical and numerical optimization technique was used to find the optimum value of TiC content using the predicted value of the responses. The tribological properties of the fabricated composites improved significantly compared to that of the magnesium matrix due to the combined effect obtainable by both reinforcements.
Hotspot Thermal Management With Flow Boiling of Refrigerant in Ultrasmall Microgaps
Authors: Nasr Mohamed H. , Green Craig E. , Kottke Peter A. , Zhang Xuchen , Sarvey Thomas E. , Joshi Yogendra K. , Bakir Muhannad S. , Fedorov Andrei G.
Published: December 2016

As integration levels increase in next generation electronics, high power density devices become more susceptible to hotspot formation, which often imposes a thermal limitation on performance. Flow boiling of R134a in two microgap heat sink configurations was investigated as a solution for hotspot thermal management: a bare microgap and inline micro-pin fin populated microgap, both with 10 μm gap height, were tested in terms of their ability to dissipate heat fluxes approaching 5 kW/cm2 at the heat source. Additional parameters investigated include mass fluxes up to 3000 kg/m2 s at inlet pressures up to 1.5 MPa and exit qualities approaching unity. The microgap testbeds investigated consist of a silicon layer which is heated from the bottom using resistive heaters and capped with glass to enable visual observation of two-phase flow regimes. Wall temperature, device thermal resistance, and pressure drop results are presented and mapped to the dominant flow regimes that were observed in the microgap.
Fast Mask Image Projection-Based Micro-Stereolithography Process for Complex Geometry
Authors: Pan Yayue , Chen Yong , Yu Zuyao
Published: December 2016

In micro-stereolithograhy (μSL), high-speed fabrication is a critical challenge due to the long delay time for refreshing resin and retaining printed microfeatures. Thus, the mask-image-projection-based micro-stereolithograhy (MIP-μSL) using the constrained surface technique is investigated in this paper for quickly recoating liquid resin. It was reported in the literature that severe damages frequently happen in the part separation process in the constrained-surface-based MIP-μSL system. To conquer this problem, a single-layer movement separation approach was adopted, and the minimum delay time for refreshing resin was experimentally characterized. The experimental results verify that, compared with the existing MIP-μSL processes, the MIP-μSL process with single-layer movement separation method developed in this paper can build microstructures with complex geometry, with a faster build speed.
Development of a Hybrid Thermoplastic Forming Process for the Manufacture of Curvilinear Surgical Blades From Bulk Metallic Glass
Authors: Zhu James , Kapoor Shiv G.
Published: December 2016

A hybrid thermoplastic forming process involving sequential micromolding and microdrawing operations is developed to manufacture the multifacet/curvilinear geometries found on most surgical blades. This is accomplished through an oblique drawing technique, i.e., drawing with a nonzero inclination angle. By applying time-varying force profiles during the drawing operation, a wide range of complex blade geometries is possible. Experiments have exhibited positive results across several multifacet and curvilinear blade geometries. Manufacturing process capabilities are quantitatively evaluated and experimental results have measured the bulk metallic glass (BMG) blade cutting edge radii to be consistently less than 15 nm, rake face surface roughness Ra to be on the order of 20 nm, and edge straightness deviations to be less than 5 μm root-mean-square (RMS) while retaining an amorphous atomic structure.
Discussion: “Multiple Analytic Solutions of Heat and Mass Transfer of Magnetohydrodynamic Slip Flow for Two Types of Viscoelastic Fluids Over a Stretching Surface” (Turkyilmazoglu, M., 2012, ASME J. Heat Transfer, 134(7), p. 071701)
Authors: Pantokratoras Asterios
Published: December 2016

This discussion concerns some errors included in the above paper.
Cold-Air Bypass Characterization for Thermal Management of Fuel Cell Gas Turbine Hybrids
Authors: Zaccaria Valentina , Tucker David , Traverso Alberto
Published: December 2016

The effect of cathode airflow variation on the dynamics of a fuel cell gas turbine hybrid system was evaluated using a cyber-physical emulator. The coupling between cathode airflow and other parameters, such as turbine speed or pressure, was analyzed comparing the results at fixed and variable speed. In particular, attention was focused on fuel cell temperatures and gradients: cathode airflow, which is generally employed for thermal management of the stack, was varied by manipulating a cold-air bypass. A significant difference was observed in the two cases in terms of turbine inlet, exhaust gas, cathode inlet, and average cell temperatures. When the turbine speed was held constant, a change in cathode airflow resulted in a strong variation in cathode inlet temperature, while average cell temperature was not significantly affected. The opposite behavior was observed at variable speed. The system dynamics were analyzed in detail in order to explain this difference. Open-loop response was analyzed in this work for its essential role in system identification. However, a significant difference was observed between fixed and variable speed cases, because of the high coupling between turbine speed and cathode airflow. These results can give a helpful insight of system dynamics and control requirements. Cold-air valve bypass position also showed a strong effect on surge margin and pressure dynamics in both cases.
New Conservation Laws, Lagrangian Forms, and Exact Solutions of Modified Emden Equation
Authors: Gün Polat Gülden , Özer Teoman
Published: December 2016

This study deals with the determination of Lagrangians, first integrals, and integrating factors of the modified Emden equation by using Jacobi and Prelle–Singer methods based on the Lie symmetries and λ-symmetries. It is shown that the Jacobi method enables us to obtain Jacobi last multipliers by means of the Lie symmetries of the equation. Additionally, via the Lie symmetries of modified Emden equation, we analyze some mathematical connections between λ-symmetries and Prelle–Singer method. New and nontrivial Lagrangian forms, conservation laws, and exact solutions of the equation are presented and discussed.
Cost Effects of Modular Product Family Structures: Methods and Quantification of Impacts to Support Decision Making
Authors: Ripperda Sebastian , Krause Dieter
Published: December 2016

Customer demands and global markets prompt companies to offer increasing product variety. The use of modular product structures is a possible strategy for providing the necessary external variety to the market and reducing costs by lowering internal variety within the company. Current research provides several approaches for developing modular product family structures. As modularity is a gradual property, these methods generate different product structure concepts and companies have to decide at an early stage and without detailed information which concepts to implement. Most existing modularization methods offer only little or no support for decision making, particularly in terms of cost effects. This article illustrates the cost effects of variety and modular product family structures, the various cost impacts of variety management strategies and modularization methods in a literature review. A new approach to quantify these cost effects to support concept selection during modular product family design is introduced.
Cutting Tool Parameters of Cylindrical Skiving Cutter With Sharpening Angle for Internal Gears
Authors: Moriwaki Ichiro , Osafune Tsukasa , Nakamura Morimasa , Funamoto Masami , Uriu Koichiro , Murakami Takanori , Nagata Eiri , Kurita Nobuaki , Tachikawa Tomokazu , Kobayashi Yoshinori
Published: December 2016

Gear skiving is a technique proposed a long time ago for cutting internal gears at high productivity. Until recently, many problems have prevented its widespread use. With current technological breakthroughs, however, skiving is drawing attention again. The present paper describes cutting tool parameters, which could be vital for the optimum design of skiving cutters. Cutting tool parameters include depth of cut, rake angle, and clearance angle at each point on a cutting edge. They continuously change with progress in the cutting process. The parameters are defined on the basis of an oblique cutting model, which is a three-dimensional extension of an orthogonal cutting model. The example calculations in this study revealed the following features: Although rake angles almost always remain negative, clearance angles remain positive. At the points where clearance angles are large, depths of cut are large, but rake angles are small (i.e., largely negative). The decrease in shaft angle between the cutter and working blank axes increases depths of cut and clearance angles, while reducing rake angles (i.e., yields largely negative rake angles). Meanwhile, the increase in cutter tool face offset; i.e., the axial position of a tool face measured from a reference point on the conjugate pinion, narrows the area where depths of cut and clearance angles are small, but rake angles become largely negative. These parameters could be useful for evaluating tool cutting efficiencies in internal gear skiving.
Al2O3/SiO2 nanolaminate for a gate oxide in a GaN-based MOS device
Authors: Kikuta Daigo , Itoh Kenji , Narita Tetsuo , Mori Tomohiko
Published: December 2016

In this study, the authors systematically investigate the electrical properties and reliability of Al2O3/SiO2 nanolaminate films with different compositions on GaN. Leakage current in the nanolaminates was suppressed by the higher SiO2 content due to the enhancement of conduction band offset between the nanolaminate and GaN. The interface-trap density (Dit) at the nanolaminates/GaN was as good as those at the Al2O3/GaN and SiO2/GaN interfaces. The lifetime of the nanolaminates increased with increasing SiO2 content. In addition, the authors demonstrated that the nanolaminate with thickness ratio of 0.21 had almost same lifetime as the Al2O3 under same equivalent electric field.
Connecting the grain-shearing mechanism of wave propagation in marine sediments to fractional order wave equations
Authors: Pandey Vikash , Holm Sverre
Published: December 2016

The characteristic time-dependent viscosity of the intergranular pore-fluid in Buckingham's grain-shearing (GS) model [Buckingham, J. Acoust. Soc. Am. 108, 2796–2815 (2000)] is identified as the property of rheopecty. The property corresponds to a rare type of a non-Newtonian fluid in rheology which has largely remained unexplored. The material impulse response function from the GS model is found to be similar to the power-law memory kernel which is inherent in the framework of fractional calculus. The compressional wave equation and the shear wave equation derived from the GS model are shown to take the form of the Kelvin-Voigt fractional-derivative wave equation and the fractional diffusion-wave equation, respectively. Therefore, an analogy is drawn between the dispersion relations obtained from the fractional framework and those from the GS model to establish the equivalence of the respective wave equations. Further, a physical interpretation of the characteristic fractional order present in the wave equations is inferred from the GS model. The overall goal is to show that fractional calculus is not just a mathematical framework which can be used to curve-fit the complex behavior of materials. Rather, it can also be derived from real physical processes as illustrated in this work by the example of GS.
Dramatic influence of patchy attractions on short-time protein diffusion under crowded conditions
Authors: Bucciarelli Saskia , Myung Jin Suk , Farago Bela , Das Shibananda , Vliegenthart Gerard A. , Holderer Olaf , Winkler Roland G. , Schurtenberger Peter , Gompper Gerhard , Stradner Anna
Published: December 2016

We show that weak patchy attractions markedly slow down protein diffusion under conditions prevailing in living cells.
Breakdown of Hooke’s law of elasticity at the Mott critical endpoint in an organic conductor
Authors: Gati Elena , Garst Markus , Manna Rudra S. , Tutsch Ulrich , Wolf Bernd , Bartosch Lorenz , Schubert Harald , Sasaki Takahiko , Schlueter John A. , Lang Michael
Published: December 2016

The coupling of the critical electronic system to a compressible lattice is found to drastically alter the Mott criticality.
A single splice site mutation in human-specific
ARHGAP11B
causes basal progenitor amplification
Authors: Florio Marta , Namba Takashi , Pääbo Svante , Hiller Michael , Huttner Wieland B.
Published: December 2016

Single nucleotide substitution played important role in evolutionary expansion of human neocortex.
U.S. Congress wants to know the weather weeks ahead
Authors: Voosen Paul
Published: December 2016

Bill targets seasonal forecasts and NOAA's pricey satellites.
A fast radio boom
Authors: Kaspi Victoria M.
Published: December 2016

Bright distant radio bursts are excellent probes of the intergalactic medium
Active sites in heterogeneous ice nucleation—the example of K-rich feldspars
Authors: Kiselev Alexei , Bachmann Felix , Pedevilla Philipp , Cox Stephen J. , Michaelides Angelos , Gerthsen Dagmar , Leisner Thomas
Published: December 2016

From dust to ice

How does ice form on the surfaces of aerosol particles? The process is important for climate and atmospheric properties but poorly understood at the molecular level, in part because the nature of the sites where ice growth begins is unclear. Kiselev
et al.
used electron microscopy and computer simulations to study the deposition of aligned ice crystals on feldspar, a major component of mineral dust (see the Perspective by Murray). Surface defects of the feldspar were responsible for its high ice-nucleation efficiency.

Science
, this issue p.
367
; see also p.
346
Quantum optical circulator controlled by a single chirally coupled atom
Authors: Scheucher Michael , Hilico Adèle , Will Elisa , Volz Jürgen , Rauschenbeutel Arno
Published: December 2016

A quantum optical circulator

A circulator is a passive three- or four-port device that routes signals according to a simple protocol: If the ports are numbered in ascending order, a signal that enters the circulator through port 1, 2, 3, or 4 exits it through port 2, 3, 4, or 1, respectively. Scheucher
et al.
demonstrate an integrated optical circulator that operates by using the internal quantum state of a single atom (see the Perspective by Munro and Nemoto). Moreover, the routing can be reversed by flipping the atomic spin. Such an integrated optical device may be important for routing and processing quantum information in scalable integrated optical circuits.

Science
, this issue p.
1577
; see also p.
1532
Encoding vocal culture
Authors: Tchernichovski Ofer , Lipkind Dina
Published: December 2016

Neuronal encoding of birdsong promotes learning and species specificity
The smoking gun of the ice ages
Authors: Hodell David A.
Published: December 2016

Forty years ago, a seminal paper showed that small changes in Earth's orbit are key to understanding ice age cycles
Comparative Evaluation of Four Phenotypic Tests for Detection of Carbapenemase-Producing Gram-Negative Bacteria
Authors: Noël Audrey , Huang Te-Din , Berhin Catherine , Hoebeke Martin , Bouchahrouf Warda , Yunus Sami , Bogaerts Pierre , Glupczynski Youri
Published: December 2016

Four screening assays aimed for rapid detection of carbapenemase production from Gram-negative bacterial isolates, i.e., the Neo-Rapid Carb kit (Rosco Diagnostica A/S), the Rapidec Carba NP test (bioMérieux SA), the β Carba test (Bio-Rad Laboratories N.V.), and a homemade electrochemical assay (BYG Carba test) were evaluated against a panel comprising 328 clinical isolates (
Enterobacteriaceae
[
n
= 198] and nonfermentative Gram-negative bacilli [
n
= 130]) with previously characterized resistance mechanisms to carbapenems. Among
Enterobacteriaceae
isolates, the BYG Carba test and the β Carba test showed excellent sensitivities (respectively, 100% and 97.3%) and specificities (respectively, 98.9% and 97.7%). The two other assays yielded poorer performances with sensitivity and specificity of 91.9% and 83.9% for the Rapidec Carba NP test and of 89.2% and 89.7% for the Neo-Rapid Carb kit, respectively. Among
Pseudomonas
spp., sensitivities and specificities ranged, respectively, from 87.3% to 92.7% and from 88.2% to 94.1%. Finally, all tests performed poorly against
Acinetobacter
spp., with sensitivities and specificities, respectively, ranging from 27.3% to 75.8% and from 75 to 100%. Among commercially available assays, the β Carba test appeared to be the most convenient for routine use and showed the best overall performances, especially against OXA-48-like producers. The excellent performance of the BYG Carba test against
Enterobacteriaceae
was confirmed (100% sensitivity and 98.9% specificity).
Use of Recombinant Antigens for Sensitive Serodiagnosis of American Tegumentary Leishmaniasis Caused by Different Leishmania Species
Authors: Sato Camila Massae , Sanchez Maria Carmen Arroyo , Celeste Beatriz Julieta , Duthie Malcolm S. , Guderian Jeffrey , Reed Steven G. , de Brito Maria Edileuza Felinto , Campos Marliane Batista , de Souza Encarnação Helia Valeria , Guerra Jorge , de Mesquita Tirza Gabrielle Ramos , Pinheiro Suzana Kanawati , Ramasawmy Rajendranath , Silveira Fernando Tobias , de Assis Souza Marina , Goto Hiro
Published: December 2016

American tegumentary leishmaniasis (ATL) (also known as cutaneous leishmaniasis [CL]) is caused by various species of protozoa of the genus
Leishmania
. The diagnosis is achieved on a clinical, epidemiological, and pathological basis, supported by positive parasitological exams and demonstration of leishmanin delayed-type hypersensitivity. Serological assays are not routinely used in the diagnosis because many are considered to have low sensitivity and the particular
Leishmania
species causing the disease can lead to variable performance. In the present study, we generated recombinant versions of two highly conserved
Leishmania
proteins,
Leishmania
(
Viannia
)
braziliensis
-derived Lb8E and Lb6H, and evaluated both in enzyme-linked immunosorbent assays (ELISA). Recombinant Lb6H (rLb6H) had better performance and reacted with 100.0% of the ATL and 89.4% of the VL samples. These reactions with rLb6H were highly specific (98.5%) when compared against those for samples from healthy control individuals. We then assessed rLb6H against sera from ATL patients infected with different species of
Leishmania
prevalent in Brazil [
Leishmania
(
Leishmania
)
amazonensis
,
L
. (
Viannia
)
braziliensis
, and
L
. (
V
.)
guyanensis
] and samples from patients with other infectious diseases. In analyses of 500 sera, ELISA using rLb6H detected all 219 ATL samples (sensitivity of 100.0%) with an overall specificity of 93.9% (considering healthy individuals and other infectious diseases patients). Only a minority of samples from Chagas disease patients possessed antibodies against rLb6H, and all of these responses were low (with a highest reactivity index of 2.2). Taken together, our data support further evaluation of rLb6H and the potential for its routine use in the serological diagnosis of ATL.
Clinical Evaluation and Cost Analysis of Great Basin Shiga Toxin Direct Molecular Assay for Detection of Shiga Toxin-Producing Escherichia coli in Diarrheal Stool Specimens
Authors: Faron Matthew L. , Ledeboer Nathan A. , Connolly Jessica , Granato Paul A. , Alkins Brenda R. , Dien Bard Jennifer , Daly Judy A. , Young Stephen , Buchan Blake W.
Published: December 2016

The Shiga Toxin Direct molecular assay (ST Direct) relies on nucleic acid amplification and solid array-based amplicon detection to identify Shiga toxin-producing
Escherichia coli
(STEC) in preserved stool specimens. Genes encoding Shiga toxin (
stx
1
and
stx
2
), as well as the
E. coli
serotype O:157-specific marker
rfbE
, are simultaneously detected within 2 h. ST Direct was evaluated using 1,084 prospectively collected preserved stool specimens across five clinical centers. An additional 55 retrospectively collected, frozen specimens were included to increase the number of positive specimens evaluated. Results were compared to results from routine culture and an enzyme immunoassay (EIA) specific for the recovery and identification of STEC. ST Direct was found to be 93.2% sensitive and 99.3% specific for detection of
stx
1
and
stx
2
and 95.7% sensitive and 99.3% specific for detection of
E. coli
serotype O:157. All specimens with false-positive results were found to contain
stx
1
or
stx
2
or were found to be positive for serotype O:157 when analyzed using alternative molecular methods. All 4 false-negative
stx
1
or
stx
2
results were reported for frozen, retrospectively tested specimens. In all cases, the specimens tested positive for
stx
by an alternative FDA-cleared nucleic acid amplification test (NAAT) but were negative for
stx
1
and
stx
2
following nucleic acid sequence analysis. Based on these data, culture and EIA-based methods for detection of STEC are only 33% sensitive compared to molecular tests. A retrospective cost analysis demonstrated 59% of the cost of routine stool culture to be attributable to the identification of STEC. Taken together, these data suggest that ST Direct may provide a cost-effective, rapid molecular alternative to routine culture for the identification of STEC in preserved stool specimens.
Evaluation of Correlation between Pretest Probability for Clostridium difficile Infection and Clostridium difficile Enzyme Immunoassay Results
Authors: Kwon Jennie H. , Reske Kimberly A. , Hink Tiffany , Burnham Carey-Ann D. , Dubberke Erik R.
Published: December 2016

The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients tested for
Clostridium difficile
and determine the correlation between pretest probability for
C. difficile
infection (CDI) and assay results. Patients with testing ordered for
C. difficile
were enrolled and assigned a high, medium, or low pretest probability of CDI based on clinical evaluation, laboratory, and imaging results. Stool was tested for
C. difficile
by toxin enzyme immunoassay (EIA) and toxigenic culture (TC). Chi-square analyses and the log rank test were utilized. Among the 111 patients enrolled, stool samples from nine were TC positive and four were EIA positive. Sixty-one (55%) patients had clinically significant diarrhea, 19 (17%) patients did not, and clinically significant diarrhea could not be determined for 31 (28%) patients. Seventy-two (65%) patients were assessed as having a low pretest probability of having CDI, 34 (31%) as having a medium probability, and 5 (5%) as having a high probability. None of the patients with low pretest probabilities had a positive EIA, but four were TC positive. None of the seven patients with a positive TC but a negative index EIA developed CDI within 30 days after the index test or died within 90 days after the index toxin EIA date. Pretest probability for CDI should be considered prior to ordering
C. difficile
testing and must be taken into account when interpreting test results. CDI is a clinical diagnosis supported by laboratory data, and the detection of toxigenic
C. difficile
in stool does not necessarily confirm the diagnosis of CDI.
Reassortment between Swine H3N2 and 2009 Pandemic H1N1 in the United States Resulted in Influenza A Viruses with Diverse Genetic Constellations with Variable Virulence in Pigs
Authors: Rajão Daniela S. , Walia Rasna R. , Campbell Brian , Gauger Phillip C. , Janas-Martindale Alicia , Killian Mary Lea , Vincent Amy L.
Published: December 2016

Repeated spillovers of the H1N1 pandemic virus (H1N1pdm09) from humans to pigs resulted in substantial evolution of influenza A viruses infecting swine, contributing to the genetic and antigenic diversity of influenza A viruses (IAV) currently circulating in swine. The reassortment with endemic swine viruses and maintenance of some of the H1N1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. Here, we performed a whole-genome phylogenetic analysis of 368 IAV circulating in swine from 2009 to 2016 in the United States. We identified 44 different genotypes, with the most common genotype (32.33%) containing a clade IV-A HA gene, a 2002-lineage NA gene, an M-pdm09 gene, and remaining gene segments of triple reassortant internal gene (TRIG) origin. To understand how different genetic constellations may relate to viral fitness, we compared the pathogenesis and transmission in pigs of six representative genotypes. Although all six genotypes efficiently infected pigs, they resulted in different degrees of pathology and viral shedding. These results highlight the vast H3N2 genetic diversity circulating in U.S. swine after 2009. This diversity has important implications in the control of this disease by the swine industry, as well as a potential risk for public health if swine-adapted viruses with H1N1pdm09 genes have an increased risk to humans, as occurred in the 2011-2012 and 2016 human variant H3N2v cases associated with exhibition swine.

IMPORTANCE
People continue to spread the 2009 H1N1 pandemic (H1N1pdm09) IAV to pigs, allowing H1N1pdm09 to reassort with endemic swine IAV. In this study, we determined the 8 gene combinations of swine H3N2 IAV detected from 2009 to 2016. We identified 44 different genotypes of H3N2, the majority of which contained at least one H1N1pdm09 gene segment. We compared six representative genotypes of H3N2 in pigs. All six genotypes efficiently infected pigs, but they resulted in different degrees of lung damage and viral shedding. These results highlight the vast genetic diversity of H3N2 circulating in U.S. swine after 2009, with important implications for the control of IAV for the swine industry. Because H1N1pdm09 is also highly adapted to humans, these swine viruses pose a potential risk to public health if swine-adapted viruses with H1N1pdm09 genes also have an increased risk for human infection.
Amino Acid Mutations in the NS4A Region of Hepatitis C Virus Contribute to Viral Replication and Infectious Virus Production
Authors: Murayama Asako , Sugiyama Nao , Suzuki Ryosuke , Moriyama Masaki , Nakamura Noriko , Mochizuki Hidenori , Wakita Takaji , Kato Takanobu
Published: December 2016

Hepatitis C virus (HCV) strain JFH-1, which belongs to genotype 2a, replicates autonomously in cultured cells, whereas another genotype 2a strain, J6CF, does not. Previously, we found that replacement of the NS3 helicase and NS5B-to-3′X regions of J6CF with those of JFH-1 confers J6CF replication competence. In this study, we aimed to identify the minimum modifications within these genomic regions needed to establish replication-competent J6CF. We previously identified 4 mutations in the NS5B-to-3′X region that could be used instead of replacement of this region to confer J6CF replication competence. Here, we induced cell culture-adaptive mutations in J6CF by the long-term culture of J6CF/JFH-1 chimeras composed of JFH-1 NS5B-to-3′X or individual parts of this but not the NS3 helicase region. After 2 months of culture, efficient HCV replication and infectious virus production in chimeric RNA-transfected cells were observed, and several amino acid mutations in NS4A were identified in replicating HCV genomes. The introduction of NS4A mutations into the J6CF/JFH-1 chimeras enhanced viral replication and infectious virus production. Immunofluorescence microscopy demonstrated that some of these mutations altered the subcellular localization of the coexpressed NS3 protein and affected the interaction between NS3 and NS4A. Finally, introduction of the most effective NS4A mutation, A1680E, into J6CF contributed to its replication competence in cultured cells when introduced in conjunction with four previously identified adaptive mutations in the NS5B-to-3′X region. In conclusion, we identified an adaptive mutation in NS4A that confers J6CF replication competence when introduced in conjunction with 4 mutations in NS5B-to-3′X and established a replication-competent J6CF strain with minimum essential modifications in cultured cells.

IMPORTANCE
The HCV cell culture system using the JFH-1 strain and HuH-7 cells can be used to assess the complete HCV life cycle in cultured cells. This cell culture system has been used to develop direct-acting antivirals against HCV, and the ability to use various HCV strains within this system is important for future studies. In this study, we aimed to establish a novel HCV cell culture system using another HCV genotype 2a strain, J6CF, which replicates in chimpanzees but not in cultured cells. We identified an effective cell culture-adaptive mutation in NS4A and established a replication-competent J6CF strain in cultured cells with minimum essential modifications. The described strategy can be used in establishing a novel HCV cell culture system, and the replication-competent J6CF clone composed of the minimum essential modifications needed for cell culture adaptation will be valuable as another representative of genotype 2a strains.
High Prevalence of Infectious Adeno-associated Virus (AAV) in Human Peripheral Blood Mononuclear Cells Indicative of T Lymphocytes as Sites of AAV Persistence
Authors: Hüser Daniela , Khalid Dina , Lutter Timo , Hammer Eva-Maria , Weger Stefan , Heßler Melanie , Kalus Ulrich , Tauchmann Yvonne , Hensel-Wiegel Karin , Lassner Dirk , Heilbronn Regine
Published: December 2016

Seroepidemiology shows that infections with adeno-associated virus (AAV) are widespread, but diverse AAV serotypes isolated from humans or nonhuman primates have so far not been proven to be causes of human disease. In view of the increasing success of AAV-derived vectors in human gene therapy, definition of the
in vivo
sites of wild-type AAV persistence and the clinical consequences of its reactivation is becoming increasingly urgent. Here, we identify the presumed cell type for AAV persistence in the human host by highly sensitive AAV PCRs developed for the full spectrum of human AAV serotypes. In genomic-DNA samples from leukocytes of 243 healthy blood donors, 34% were found to be AAV positive, predominantly AAV type 2 (AAV2) (77%), AAV5 (19%), and additional serotypes. Roughly 11% of the blood donors had mixed AAV infections. AAV prevalence was dramatically increased in immunosuppressed patients, 76% of whom were AAV positive. Of these, at least 45% displayed mixed infections. Follow-up of single blood donors over 2 years allowed repeated detection of the initial and/or additional AAV serotypes, suggestive of fluctuating, persistent infection. Leukocyte separation revealed that AAV resided in CD3
+
T lymphocytes, perceived as the putative
in vivo
site of AAV persistence. Moreover, infectious AAVs of various serotypes could be rescued and propagated from numerous samples. The high prevalence and broad spectrum of human AAVs in leukocytes closely follow AAV seroepidemiology. Immunosuppression obviously enhances AAV replication in parallel with activation of human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6), reminiscent of herpesvirus-induced AAV activation.

IMPORTANCE
Adeno-associated virus is viewed as apathogenic and replication defective, requiring coinfection with adenovirus or herpesvirus for productive infection.
In vivo
persistence of a defective virus requires latency in specialized cell types to escape the host immune response until viral spread becomes possible. Reactivation from latency can be induced by diverse stimuli, including infections, typically induced upon host immunosuppression. We show for the first time that infectious AAV is highly prevalent in human leukocytes, specifically T lymphocytes, and that AAV is strongly amplified upon immunosuppression, along with reactivation of latent human herpesviruses. In the absence of an animal model to study the AAV life cycle, our findings in the human host will advance the understanding of AAV latency, reactivation, and
in vivo
pathogenesis.
Temporal and Racial Differences Associated with Atopic Dermatitis Staphylococcus aureus and Encoded Virulence Factors
Authors: Merriman Joseph A. , Mueller Elizabeth A. , Cahill Michael P. , Beck Lisa A. , Paller Amy S. , Hanifin Jon M. , Ong Peck Y. , Schneider Lynda , Babineau Denise C. , David Gloria , Lockhart Alexandre , Artis Keli , Leung Donald Y. M. , Schlievert Patrick M.
Published: December 2016

Monitoring pathogen emergence provides insight into how pathogens adapt in the human population. Secreted virulence factors, important contributors to infections, may differ in a manner dependent on the strain and host. Temporal changes of
Staphylococcus aureus
toxigenic potential, for example, in encoding toxic shock syndrome toxin 1 (TSST-1), contributed to an epidemic of TSS with significant health impact. This study monitored changes in atopic dermatitis (AD)
S. aureus
isolates and demonstrated both temporal and host infection differences according to host race based on secreted superantigen potential. The current temporal increase in enterotoxin gene cluster superantigen prevalence and lack of the gene encoding TSST-1 in AAs predict differences in infection types and presentations.
Late Quaternary climatic control of Lake Baikal (Russia) turbidite systems: Implications for turbidite systems worldwide
Authors: Evangelinos Dimitris , Nelson C. Hans , Escutia Carlota , De Batist Marc , Khlystov Oleg
Published: December 2016

Lake Baikal (Russia) contains a variety of turbidite systems in different tectonic and depositional settings that provide tests for the role of Quaternary climatic change on turbidite system growth. During Pleistocene glacial climates, all types of systems exhibit increased sediment supply (high sedimentation rates, high net sand percent, thick sand turbidites) and progradation. During Holocene interglacial climate, all systems exhibit reduced sediment supply and retreat. Seismic profiles from the large Selenga Fan and small Tompuda Fan show (1) maximum fan growth during the late Pleistocene glacial melt time, where lobes and large channels reached the distal outer fan, and (2) fan retreat during the transition to the fully developed Holocene interglacial climate. For example, the Selenga Fan surface lobes backstepped ∼55 km from the distal outer fan to the distal inner fan, and the large outer fan surface channel (∼750 m wide, ∼20 m levee relief) evolved to a smaller surface channel (∼450 m wide, ∼13 m levee relief) that extended only to the end of the inner fan. These results show that Quaternary climate controls the growth of the Lake Baikal turbidite systems in a setting where there are no significant water-level changes, which often are cited as the main control on turbidite system growth. The Lake Baikal and other marine turbidite systems suggest that climatic control of sediment supply, unrelated to sea-level lowering and tectonic effects, may have been a much more important control for turbidite systems than previously believed, not only during the Pleistocene, but perhaps also for ancient systems.
Bladder agenesis, ectopic ureters and a multicystic dysplastic horseshoe kidney in one twin newborn with normal amniotic fluid index in utero
Authors: Khan Marium Naveed , Walsh William F
Published: December 2016

A monochorionic-diamniotic twin baby presented with intrauterine growth restriction and anuria. The baby was found to have bladder agenesis, a pelvic dysplastic horseshoe kidney, vertebral anomalies, a ventricular septal defect and facial dysmorphisms. It was surprising to find no abnormalities in amniotic fluid indices prenatally, suggesting the possibility of urine output that declined as the pregnancy proceeded. Some degree of twin-to-twin transfusion of amniotic fluid was also possible, which could have rescued the oligohydramnios known to be associated with kidney and urinary tract abnormalities. It was also notable that there was no abnormality in respiratory function, especially since further investigations revealed close to no kidney function. The intrauterine growth restriction (IUGR) along with the multiple anomalies found made the baby unsuitable for dialysis and transplant, and the decision of transition to palliative care was made.
Forgetting to remember: hypoglycaemic encephalopathy
Authors: Martin Tomas D , Canepa Carlo
Published: December 2016

A 37-year-old woman with a history of poorly controlled type 1 diabetes presented acutely with a decreased Glasgow Coma Scale and a diagnosis of hypoglycaemic brain injury. Her MRI highlighted bilateral hippocampi diffusion restriction and T2 hyperintensity. Clinically, she had a marked cognitive deficit, particularly of short-term, anterograde amnesia. She was managed conservatively and with intensive rehabilitation.
Management of splenic ectopic pregnancy presenting with massive haemoperitoneum
Authors: Greenbaum Alissa , Miskimins Richard , Coffman Brittany , Paul Jasmeet
Published: December 2016

Abdominal ectopic pregnancy (EP) accounts for only 1.3% of EPs and occurs when a fertilised ovum implants in an extrapelvic peritoneal location. Primary splenic pregnancy is a rare type of abdominal EP, with only 16 cases previously reported in the literature. Early diagnosis is essential as delay in treatment carries significant potential for morbidity and mortality. We present the case of a 27-year-old woman presenting with left upper quadrant abdominal pain, elevated human chorionic gonadotropin levels, absence of intrauterine gestational sac and massive haemoperitoneum on transvaginal ultrasound. The patient underwent emergent surgical exploration for high suspicion of ruptured abdominal EP. An open splenectomy was performed when the source of bleeding was confirmed to originate from the left upper quadrant. Final pathology confirmed subcapsular gestational sac implantation within the spleen. While two cases of medical management have been reported, splenectomy remains the current definitive management of rare cases of primary splenic pregnancy.