bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of liver stiffness, spleen stiffness, and LS‐spleen diameter to platelet ratio score in detection of esophageal varices: Systemic review and meta‐analysis
Authors: Manatsathit Wuttiporn , Samant Hrishikesh , Kapur Saurabh , Ingviya Thammasin , Esmadi Mohammad , Wijarnpreecha Karn , McCashland Timothy
Published: May 2018

Background and Aim

There is increasing evidence of non‐invasive measurement using elastography such liver stiffness (LS), spleen stiffness (SS), and LS‐spleen diameter to platelet ratio score (LSPS) for detection of esophageal varices (EV); however, data regarding comparison between these three parameters are limited.

Methods

We performed a systemic review and meta‐analysis of studies evaluating performance of LS, SS, and LSPS for detection of EV and high risk/clinically significant EV (HREV). Pooled sensitivity, specificity, log diagnostic odd ratio (LDOR), and area under the receiver operating characteristic curve (AUC) of LS, SS, and LSPS for detection of EV and HREV were analyzed and compared. Publication bias was assessed by Deeks' funnel plot.

Results

SS and LSPS were superior to LS for detection of EV with higher sensitivity (0.90 and 0.91 vs 0.85), specificity (0.73 and 0.76 vs 0.64), LDOR (3.24 and 3.35 vs 2.26), and AUC (0.899 and 0.851 vs 0.817). For HREV, SS had the highest sensitivity (0.87) followed by LS (0.85) and LSPS (0.82); however, SS had the lowest specificity (0.52), LDOR (2.09), and AUC (0.807) whereas LSPS had the highest specificity (0.77), LDOR (2.74), and AUC (0.861).

Conclusion

For detection of EV, we prefer using LSPS and SS over LS when available, while LS, SS, and LSPS cannot be recommended for detection of HREV due to their moderate sensitivity and specificity.
Combined Inflammation and Metabolism Biomarker Indices of Robust and Impaired Physical Function in Older Adults
Authors: Zuo Xintong , Luciano Alison , Pieper Carl F. , Bain James R , Kraus Virginia B. , Kraus William E. , Morey Miriam C. , Cohen Harvey J.
Published: May 2018

Objectives

To determine whether combinations of inflammatory markers are related to physical function.

Design and subjects

secondary analysis of baseline of three observational studies of community‐dwelling older adults

Measurements

The baseline data from 3 cohorts of older adults with different health and disease status were employed. Twenty markers of inflammation and metabolism were individually assessed for correlation with usual gait speed and were separated into robust and impairment quartiles. For the robustness and impairment indices, individual markers were selected using step‐wise regression over bootstrapping iterations, and regression coefficients were estimated for the markers individually and collectively as an additive score.

Results

We developed a robustness index involving 6 markers and an impairment index involving 8 markers corresponding positively and negatively with gait speed. Two markers, glycine and tumor necrosis factor receptor 1 (TNFR1), appeared only in the robustness index, and TNFR2; regulated on activation, normal T‐cell expressed and secreted; the amino acid factor; and matrix metallopeptidase 3; appeared only in the impairment index.

Conclusion

Indices of biomarkers were associated with robust and impaired physical performance but differ, in composition suggesting potential biological differences that may contribute to robustness and impairment.
CMBS and Conflicts of Interest: Evidence from Ownership Changes for Servicers
Authors: WONG MAISY
Published: May 2018

Self‐dealing is potentially important but difficult to measure. In this paper, I study special servicers in commercial mortgage‐backed securities (CMBS), which sell distressed assets on behalf of bondholders. Around 2010, ownership changes of four major servicers raised concerns that they may direct benefits to new owners' affiliates (buyers and service providers). Loans liquidated after ownership changes have greater loss rates than before (8 percentage points (p.p.), $2.3 billion in losses), relative to other (placebo) servicers. Together with a case study that tracks self‐dealing purchases, the findings point to potential steering conflicts that could incentivize tunneling through fees to service providers.
Organizational Attributes Associated With Medicare ACO Quality Performance
Authors: Zhu Xi , Mueller Keith , Huang Huang , Ullrich Fred , Vaughn Thomas , MacKinney A Clinton
Published: May 2018

Purpose

To evaluate associations between geographic, structural, and service‐provision attributes of Accountable Care Organizations (ACOs) participating in the Medicare Shared Savings Program (MSSP) and the ACOs’ quality performance.

Methodology

We conducted cross‐sectional and longitudinal analyses of ACO quality performance using data from the Centers for Medicare and Medicaid Services and additional sources. The sample included 322 and 385 MSSP ACOs that had successfully reported quality measures in 2014 and 2015, respectively.

Results

Results show that after adjusting for other organizational factors, rural ACOs’ average quality score was comparable to that of ACOs serving other geographic categories. ACOs with hospital‐system sponsorship, larger beneficiary panels, and higher posthospitalization follow‐up rates achieved better quality performance.

Conclusion

There is no significant difference in average quality performance between rural ACOs and other ACOs after adjusting for structural and service‐provision factors. MSSP ACO quality performance is positively associated with hospital‐system sponsorship, beneficiary panel size, and posthospitalization follow‐up rate.
Reliability of sleep spindle measurements in adolescents: How many nights are necessary?
Authors: Reynolds Chelsea M. , Gradisar Michael , Short Michelle A.
Published: May 2018

Evidence of night‐to‐night variation in adolescent sleep spindle characteristics is lacking. Twelve adolescents (M = 15.8 ± 0.8 years, eight males) participated in a laboratory study involving 9 nights with 10 hr sleep opportunity. Sleep electroencephalograph was analysed and intra‐class coefficients calculated to determine the reliability of sleep spindles across multiple nights of recording. Slow spindle amplitude and fast spindle density, duration and amplitude characteristics all had acceptable reliability within a single night of sleep recording. Slow spindle density and duration measurements needed a minimum of 4 and 2 nights, respectively, for reliable estimation. Theoretical and methodological implications are discussed.
Use of basal and TRH‐stimulated plasma growth hormone concentrations to differentiate between primary hypothyroidism and nonthyroidal illness in dogs
Authors: Pijnacker Tera , Kooistra Hans S. , Vermeulen Cathelijne F. , van der Vinne Merel , Prins Marrit , Galac Sara , Mol Jan A.
Published: May 2018

Background

A low plasma total thyroxine (TT4) concentration in combination with a plasma TSH concentration within reference range does not distinguish between hypothyroidism and nonthyroidal illness (NTI) in dogs. Hypothyroidism is associated with TSH‐releasing hormone (TRH)‐induced increased release of growth hormone (GH).

Hypothesis

Basal and TRH‐induced plasma GH concentrations can be used to distinguish hypothyroid dogs from NTI dogs.

Animals

Twenty‐one dogs with signs consistent with hypothyroidism, a low plasma TT4concentration, and a plasma TSH concentration within reference interval.

Methods

Case control study. Thyroid scintigraphy was performed to classify dogs as having hypothyroidism or NTI. All dogs underwent a TRH stimulation test with measurement of plasma concentrations of GH and TSH before and 30 and 45 minutes after IV administration of TRH.

Results

Eleven of the dogs were classified as hypothyroid and 10 as having NTI. Basal plasma GH concentration in the hypothyroid dogs (3.2 μg/l; range, 2.0 to 12.5 μg/l) was significantly higher (p<0.001) than that in the NTI dogs (.73 μg/l; range, .45 to 2.3 μg/l), with minimal overlap, and increased (p=.009) after TRH administration in hypothyroid dogs, whereas it did not change in NTI dogs. At T=45, plasma GH concentrations in hypothyroid dogs and NTI dogs did not overlap. The plasma TSH concentration did not change significantly after TRH administration in hypothyroid dogs, whereas it increased (p<.001) in NTI dogs. At T=45, there was no overlap in percentage TSH increase from baseline between hypothyroid dogs.

Conclusions and Clinical Importance

Measurement of basal plasma GH concentration and concentrations of GH and TSH after TRH stimulation can distinguish between hypothyroidism and NTI in dogs.
Reversal of hypercoagulability in patients with HCV‐related cirrhosis after treatment with direct‐acting antivirals
Authors: Russo Francesco Paolo , Zanetto Alberto , Campello Elena , Bulato Cristiana , Shalaby Sarah , Spiezia Luca , Gavasso Sabrina , Franceschet Enrica , Radu Claudia , Senzolo Marco , Burra Patrizia , Lisman Ton , Simioni Paolo
Published: May 2018

Background & Aims

The long‐term impact of sustained virological response (SVR) after direct‐acting antivirals (DAAs) on the hypercoagulability associated with HCV cirrhosis is unknown. We longitudinally evaluated the effect of DAAs treatment on cirrhotic coagulopathy.

Methods

Pro‐ and anticoagulant factor levels and thrombin generation were assessed in patients with HCV‐related cirrhosis at baseline, end of therapy (EOT), at 12, 24 and 48 weeks (W) after EOT.

Results

Fifty‐eight patients were enrolled (86% Child’s A). SVR was 100%. Median factor VIII activity significantly decreased at EOT, 12 weeks and 24 weeks compared with baseline, whereas protein C significantly increased at 24 weeks and 48 weeks. Cirrhotic patients showed a slight but sustained increase in endogenous thrombin potential (ETP) with a statistically significant difference at EOT, 12 weeks, 24 weeks and 48 weeks compared with baseline. Conversely, thrombomodulin‐modified ETP was elevated before treatment and decreased over time to normal levels at 24 weeks and 48 weeks. The ETP ratio decreased slowly at EOT and 12 weeks, and was significantly decreased at 24 weeks and 48 weeks compared with baseline (P < .001 for both comparisons), being not statistically different from ETP ratio measured in healthy controls. Child’s B patients showed a significantly higher ETP ratio compared to Child’s A at baseline and did not show any significant improvement in ETP ratio through 12 weeks. Two Child’s B patients developed PVT with an incidence rate of 1.1% p‐yrs (95%CI, 0.18 to 3.58).

Conclusions

DAAs therapy in HCV‐related cirrhotic patients is associated with significant changes in thrombin generation suggesting a reversal of hypercoagulability particularly in Child’s A patients.
Five‐year profile of candidaemia at an Indian trauma centre: High rates of Candida auris blood stream infections
Authors: Mathur Purva , Hasan Fahmi , Singh Pradeep K. , Malhotra Rajesh , Walia Kamini , Chowdhary Anuradha
Published: May 2018

Candidaemia is a potentially fatal infection with varied distribution of Candida species and their antifungal susceptibility profiles. The recent emergence of Candida auris in invasive candidiasis is a cause for concern. This study describes the profile of candidaemia at an Indian tertiary care hospital and reports the emergence of C. auris. All patients diagnosed with candidaemia between 2012 and 2017 were studied. The isolates were identified using conventional methods, VITEK 2 and MALDI‐TOF MS. The isolates not identified by MALDI‐TOF were sequenced. Antifungal susceptibility testing was done by the CLSI broth microdilution method and VITEK 2. A total of 114 isolates of Candida species were analysed. Candida tropicalis (39.4%) was the most common species, followed by C. auris (17.5%), C. albicans (14%) and C. parapsilosis (11.4%). Notably, Diutina mesorugosa isolates (n = 10) were not identified by MALDI‐TOF and were confirmed by sequencing. Furthermore, 45% (n = 9) C. auris strains exhibited low MICs of FLU (0.05‐4 μg/mL) and the remaining 55% (n = 11) isolates had high MICs ≥ 64 μg/mL. Also, D. mesorugosa exhibited high MICs of FLU (32 μg/mL) in 2 isolates. A high rate of errors in antifungal susceptibility was noted with the VITEK 2 as compared to the CLSI method. Candida auris was the second most prevalent species causing candidaemia warranting infection control practices to be strengthened to prevent its spread.
Reconstructing the history of nationalist cognition and everyday nationhood from personal accounts
Authors: Moreno‐Almendral Raúl
Published: May 2018

New approaches to nationalism have focused on the role of human agency within nation‐building structures (nationhood from below, everyday nationalism, experiences of nation, personal nationalism, etc.). However, the development of specific methodologies is still scarce. This paper proposes the use of personal accounts (mostly journals and autobiographies, but not only) as sources for qualitative historical research in nations and nationalism. Departing from the concepts of ‘identity’, ‘experience’ and ‘memory’, it is argued that, although very problematic, these sources are a valid path to the study of nations as they are: social phenomena of discursive nature and political frame, whose real agents are individuals. When these agents narrate their lives employing the nation as a meaningful category, they are not producing mere second‐hand reflections of superior and prior realms, but are performing microhistorical acts of nation‐making that are significant for understanding any case of nation‐building. The paper includes an empirical example using British personal accounts from the Age of Revolutions (c.1780–1840).
Expression profile of markers of oxidative stress, injury and apoptosis in anti‐tuberculosis drugs induced nephrotoxicity
Authors: Sharma Radhika , Battu Priya , Singla Mandakini , Goyal Neha , Sharma Vijay L
Published: May 2018

Aim

Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA) are part of first‐line anti‐tuberculosis therapy used against infection caused by Mycobacterium tuberculosis. However, these drugs are known to be potentially harmful as these are associated with numerous side effects and when taken together their harmful outcomes are elevated in a synergistic manner. Identification of possible mechanism underlying RIF + INH + PZA induced nephrotoxicity may be advantageous in developing strategies to prevent their toxic implications.

Methods

In this study rats were distributed in two groups of six each: Control (tap water) and Toxicant (INH + RIF + PZA) in dosage derived through extrapolation from human dosage for 28 days once in a day. Antioxidant activity and histology of kidney were examined. In addition, apoptosis was also studied using pro and anti‐apoptotic markers and TUNEL staining to check nephrotoxicity.

Results

Findings indicated that combined (INH, RIF and PZA) 28 day exposure in Wistar rats caused increase in number of free radicals/ reactive oxygen species which further cause changes in levels of enzymatic antioxidants such as glutathione, Superoxide dismutase, Catalase, and Glutathione‐s‐transferase. Altered content of pro (BAD&BAX) and anti‐apoptotic genes (BCL‐2&BCL2L1) genes, TUNEL positive cells and DNA fragmentation emphasized involvement of apoptosis.

Conclusion

This study concluded that nephrotoxicity is accompanied during combinational anti‐tuberculosis drug therapy.
Characterization of photosynthetic ferredoxin from the Antarctic alga Chlamydomonas sp. UWO241 reveals novel features of cold adaptation
Authors: Cvetkovska Marina , Szyszka‐Mroz Beth , Possmayer Marc , Pittock Paula , Lajoie Gilles , Smith David R. , Hüner Norman P. A.
Published: May 2018

The objective of this work was to characterize photosynthetic ferredoxin from the Antarctic green alga Chlamydomonas sp. UWO241, a key enzyme involved in distributing photosynthetic reducing power. We hypothesize that ferredoxin possesses characteristics typical of cold‐adapted enzymes, namely increased structural flexibility and high activity at low temperatures, accompanied by low stability at moderate temperatures.

To address this objective, we purified ferredoxin from UWO241 and characterized the temperature dependence of its enzymatic activity and protein conformation. The UWO241 ferredoxin protein, RNA, and DNA sequences were compared with homologous sequences from related organisms.

We provide evidence for the duplication of the main ferredoxin gene in the UWO241 nuclear genome and the presence of two highly similar proteins. Ferredoxin from UWO241 has both high activity at low temperatures and high stability at moderate temperatures, representing a novel class of cold‐adapted enzymes.

Our study reveals novel insights into how photosynthesis functions in the cold. The presence of two distinct ferredoxin proteins in UWO241 could provide an adaptive advantage for survival at cold temperatures. The primary amino acid sequence of ferredoxin is highly conserved among photosynthetic species, and we suggest that subtle differences in sequence can lead to significant changes in activity at low temperatures.
Rate of malignant transformation of oral lichen planus: A systematic review
Authors: Giuliani Michele , Troiano Giuseppe , Cordaro Massimo , Corsalini Massimo , Gioco Gioele , Lo Muzio Lorenzo , Pignatelli Pamela , Lajolo Carlo
Published: May 2018

Objective

The aim of this study was to systematically review the literature to determine: (a) the malignant transformation rate (TR) of oral lichen planus (OLP) and its risk factors; (b) whether or not oral lichenoid lesions (OLL) have a different malignant TR.

Materials and Methods

PubMed, Scopus, and Web of Science were used as search engines: only observational, full‐length, English language studies were investigated. PRISMA protocol was used to evaluate and present results. PROSPERO registration code is CRD42016048529.

Results

Among 7,429 records screened, only 21 were included in this review. Ninety‐two of 6,559 patients developed oral squamous cell carcinoma, with an overall TR of 1.40% (1.37% for OLP and 2.43% for OLL), an annual TR of 0.20%. Female gender, red clinical forms, and tongue site seem to slightly increase the transformation risk.

Conclusions

This systematic review confirms that both OLP and OLL, the latter with a slightly higher TR, may be considered potentially malignant disorders and suggest that erosive type, female gender and tongue site should be considered as risk factors for OLP transformation. Major efforts should be done to establish strict clinical and histological criteria to diagnose OLP and to perform sounder methodological observational studies.
Transient under‐sensing of the ventricular lead during abdominal ultrasound as cause of ventricular fibrillation
Authors: Frontera Antonio , Klotz Nicolas , Martin Ruairidh , Haïssaguerre Michel , Ritter Philippe , Bordachar Pierre
Published: May 2018

Pacemaker‐induced arrhythmias represent a very rare complication. Algorithm‐induced ventricular tachycardias have been described but this report is the first to describe a ventricular fibrillation caused by transient undersensing of the ventricular lead during an abdominal ultrasound.
Water transport through tall trees: A vertically explicit, analytical model of xylem hydraulic conductance in stems
Authors: Couvreur Valentin , Ledder Glenn , Manzoni Stefano , Way Danielle A. , Muller Erik B. , Russo Sabrina E.
Published: May 2018

Trees grow by vertically extending their stems, so accurate stem hydraulic models are fundamental to understanding the hydraulic challenges faced by tall trees. Using a literature survey, we showed that many tree species exhibit continuous vertical variation in hydraulic traits. To examine the effects of this variation on hydraulic function, we developed a spatially explicit, analytical water transport model for stems. Our model allows Huber ratio, stem‐saturated conductivity, pressure at 50% loss of conductivity, leaf area, and transpiration rate to vary continuously along the hydraulic path. Predictions from our model differ from a matric flux potential model parameterized with uniform traits. Analyses show that cavitation is a whole‐stem emergent property resulting from non‐linear pressure‐conductivity feedbacks that, with gravity, cause impaired water transport to accumulate along the path. Because of the compounding effects of vertical trait variation on hydraulic function, growing proportionally more sapwood and building tapered xylem with height, as well as reducing xylem vulnerability only at branch tips while maintaining transport capacity at the stem base, can compensate for these effects. We therefore conclude that the adaptive significance of vertical variation in stem hydraulic traits is to allow trees to grow tall and tolerate operating near their hydraulic limits.
Acute kidney injury: Epidemiology, outcomes, complications, and therapeutic strategies
Authors: Negi Shigeo , Koreeda Daisuke , Kobayashi Sou , Yano Takuro , Tatsuta Koichi , Mima Toru , Shigematsu Takashi , Ohya Masaki
Published: May 2018

Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short‐ and long‐term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end‐stage renal disease requiring dialysis or transplantation is attracting increased attention.
Patients with chronic fatigue syndrome do not score higher on the autism‐spectrum quotient than healthy controls: Comparison with autism spectrum disorder
Authors: Bileviciute‐Ljungar Indre , Maroti Daniel , Bejerot Susanne
Published: May 2018

Clinically, there is an overlap of several symptoms of chronic fatigue syndrome (CFS) and autism spectrum disorder (ASD), including fatigue; brain “fog”; cognitive impairments; increased sensitivity to sound, light, and odour; increased pain and tenderness; and impaired emotional contact. Adults with CFS (n = 59) or ASD (n = 50) and healthy controls (HC; n = 53) were assessed with the Autism‐Spectrum Quotient (AQ) in a cross‐sectional study. Non‐parametric analysis was used to compare AQ scores among the groups. Univariate analysis of variance (ANCOVA) was used to identify if age, sex, or diagnostic group influenced the differences in scores. Patients with ASD scored significantly higher on the AQ than the CFS group and the HC group. No differences in AQ scores were found between the CFS and HC groups. AQ results were influenced by the diagnostic group but not by age or sex, according to ANCOVA. Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self‐report instrument, the AQ. The choice of instrument to assess autistic traits may influence the results.
A dynamic model of firm activities: Evidence from Danish manufacturing
Authors: Abreha Kaleb G.
Published: May 2018

This paper structurally estimates a dynamic discrete choice model of exporting and importing. The model provides a framework to analyse the determinants of a firm's decision to export and import while allowing for its current decision to affect its future productivity. Considering a panel of Danish manufacturing firms over the period 2000–07, a simple description of the data reveals considerable firm heterogeneity; significant export and import activity premia; frequent incidence of simultaneous exporting and importing; and high persistence in the scope of firm trading. Structural estimation of the model shows a marked difference in the demand elasticities in which export markets are characterised by more elastic demand, tougher competition and lower markup than the domestic market. The estimates also indicate that firms with larger capital holding and paying higher wages are cost‐efficient even after controlling for their productivity. Additionally, the estimates imply substantial sunk and fixed costs of exporting and importing, and these are consistent with the hypothesis of self‐selection of productive firms into trading. There also exists a positive correlation between the size of these costs and the scale of firm operation. Moreover, both exporting and importing improve firm productivity, and therefore, these learning effects further drive the self‐selection process.
Uncertainty in Multi-Scale Creep Rupture Life Modeling and a New Approach to Estimating Frequency of In-Service Inspection of Components at Elevated Temperatures
Authors: Fong Jeffrey T. , Heckert N. Alan , Filliben James J. , Cohn Marvin J.
Published: May 2018

Uncertainty in modeling the creep rupture life of a full-scale component using experimental data at microscopic (Level 1), specimen (Level 2), and full-size (Level 3) scales, is addressed by applying statistical theory of prediction intervals, and that of tolerance intervals based on the concept of coverage, p. Using a nonlinear least squares fit algorithm and the physical assumption that the one-sided Lower Tolerance Limit ( LTL ), at 95 % confidence level, of the creep rupture life, i.e., the minimum time-to-failure, minTf, of a full-scale component, cannot be negative as the lack or “Failure” of coverage ( Fp ), defined as 1 - p, approaches zero, we develop a new creep rupture life model, where the minimum time-to-failure, minTf, at extremely low “Failure” of coverage, Fp, can be estimated. Since the concept of coverage is closely related to that of an inspection strategy, and if one assumes that the predominent cause of failure of a full-size component is due to the “Failure” of inspection or coverage, it is reasonable to equate the quantity, Fp, to a Failure Probability, FP, thereby leading to a new approach of estimating the frequency of in-service inspection of a full-size component. To illustrate this approach, we include a numerical example using the published creep rupture time data of an API 579-1/ASME FFS-1 Grade 91 steel at 571.1 C (1060 F) (API-STD-530, 2007), and a linear least squares fit to generate the necessary uncertainties for ultimately performing a dynamic risk analysis, where a graphical plot of an estimate of risk with uncertainty vs. a predicted most likely date of a high consequence failure event due to creep rupture becomes available for a risk-informed inspection strategy associated with an energy-generation or chemical processing plant equipment.
Application of a Physically-Based Creep Continuum Damage Mechanics Constitutive Model to the Serviceability Assessment of a Large Bore Branch Connection
Authors: Pritchard P. G. , Perrin I. J. , Parker J. D. , Siefert J. A.
Published: May 2018

Premature creep cracking in fabricated large bore branch connections in Grade 91 steel (9Cr-1Mo-VNbN) piping continues to be a commonly observed failure mechanism in high energy applications. Failures have been observed in components fabricated to the requirements of both ASME Section I and B31.1 codes. This paper presents the application of a physically-based creep continuum damage constitutive model developed for Grade 91 steel to the assessment of a large bore fabricated branch connection. For a specific component geometry and operating conditions, model predictions for the expected location and timing of crack initiation as well as for the crack growth behavior have been made. In addition, as validation, trends in the simulated behavior are compared to information from case studies of large bore branch cracking and failure in service. The physically-based continuum damage model is shown to accurately predict both the location and timing of local crack initiation as well as the observed crack growth behavior.
Properties of INCONEL Alloy 740H for High Pressure Steam and Supercritical CO2 Applications
Authors: de Barbadillo John J. , Baker Brian A. , Gollihue Ronald D. , McCoy Stephen A.
Published: May 2018

Nickel-base alloys are required for many of the components in advanced ultra-supercritical steam and CO2 power systems operating at temperatures and pressures exceeding 1202°F (650°C) and 3.6 ksi (25 MPa). Age-hardened alloys offer a distinct advantage over traditional solid solution strengthened alloys by virtue of their significantly higher creep strength. This makes it possible to reduce wall thickness and thereby minimize total construction cost. INCONEL alloy 740H (UNS N07740) is an age-hardened alloy that was developed and extensively characterized for advanced ultra-supercritical steam boilers. Material testing by the A-USC Consortium and US Department of Energy led to ASME Code Case 2702 covering UNS N07740. Alloy 740H is the first age-hardened nickel-base alloy permitted for welded construction for use in the creep limited temperature regime. More recent development work on the alloy has focused on applications for supercritical CO2 systems. Various laboratories have reported on oxidation properties of the alloy under simulated operating conditions. This paper focuses on the manufacturing and properties of tubing and fittings that are being applied for the various advanced ultra-supercritical steam and supercritical CO2 projects now planned or underway. As many of the structures are constructed by welding, a review of welding practices is presented, including dissimilar welds and their properties.
Development of a New High-Performance Martensitic Heat-Resistant Steel for Boiler Applications
Authors: Subanović Marko , Pirón Javier , Zeller Frank , Jarrar Mahmud , Schneider André
Published: May 2018

The realization of advanced thermal power plants with increased efficiencies requires the development of new materials with enhanced capabilities in respect to high temperature strength and steam oxidation behavior. The change in the environmental policy and the increasing contribution of renewable energy sources into the public electric grid has changed the operation mode of the existing power plants in Europe. Instead of quasi stationary operation, for which the conventional thermal power plant fleet was designed, cyclic operation modes will dominate the power plant service lifetime. The creep-fatigue phenomena, however, may be responsible for significant lifetime reductions compared with the original design lifetime. Revamping of the existing power plants by application of “stronger” materials with improved steam-oxidation behavior, allowing wall thickness reduction can be a possible way to address the topic. Recently, Vallourec developed a new high-Cr ferritic-martensitic steel that combines excellent creep rupture strength properties and enhanced steam oxidation resistance of 12%Cr steels such as VM12-SHC or X20CrMoV11-1. Industrial products were successfully manufactured and the creep and steam oxidation properties were validated.
Modeling of silicon etching using Bosch process: Effects of oxygen addition on the plasma and surface properties
Authors: Le Dain Guillaume , Rhallabi Ahmed , Cardinaud Christophe , Girard Aurélie , Fernandez Marie-Claude , Boufnichel Mohamed , Roqueta Fabrice
Published: May 2018

The authors developed a tool using a multiscale approach to simulate the silicon etching using Bosch process. Their study is focused on the analysis of the effect of the oxygen addition to C4F8 plasma during the deposition pulse. This is the complementary study that the authors have recently published which was dedicated to the Bosch process under pure SF6 plasma used in etching pulse and pure C4F8 plasma used in polymer deposition pulse. Parametric study about the effect of the oxygen percentage on the reactive species flux evolution and their impact on the deposition kinetic during the deposition pulse has been performed. The simulation results reveal that for a low %O2 in a C4F8/O2 plasma mixture, the atomic fluorine density increases because of the volume reactions, especially recombinations between CFx and O which favor the production of fluorine. This leads to the decrease of CFx to F flux ratio. Ion energy distribution functions (IEDF) plotting reveals the impact of both %O2 and mass of the positive ions on the IEDF shape. Finally, both the experimental and simulation results show that in their pressure range, the addition of O2 to C4F8 plasma has a weak impact on the silicon etch profile and the etching rate, except for a high %O2 which the etch anisotropy begins to be degraded.
CCR5 adopts three homodimeric conformations that control cell surface delivery
Authors: Jin Jun , Momboisse Fanny , Boncompain Gaelle , Koensgen Florian , Zhou Zhicheng , Cordeiro Nelia , Arenzana-Seisdedos Fernando , Perez Franck , Lagane Bernard , Kellenberger Esther , Brelot Anne
Published: May 2018

Distinct dimeric conformations of the HIV-1 co-receptor CCR5 govern its appearance at the cell surface.
The receptor tyrosine kinase TrkB signals without dimerization at the plasma membrane
Authors: Zahavi Eitan Erez , Steinberg Noam , Altman Topaz , Chein Michael , Joshi Yuvraj , Gradus-Pery Tal , Perlson Eran
Published: May 2018

Contrary to other receptor tyrosine kinases, TrkB does not appear to dimerize at the plasma membrane in response to ligand.
A Systematic Approach to the Selection of the Appropriate Avibactam Concentration for Use with Ceftazidime in Broth Microdilution Susceptibility Testing
Authors: Bradford Patricia A. , Huband Michael D. , Stone Gregory G.
Published: May 2018

Selection of the avibactam concentration to combine with ceftazidime in susceptibility testing was determined using Gram-negative isolates with characterized β-lactamases predefined as susceptible or resistant, based on the known inhibition spectrum of avibactam. MIC values were determined by broth microdilution of ceftazidime with fixed concentrations and ratios of avibactam. A constant concentration of 4 μg/ml of avibactam was selected for susceptibility testing with ceftazidime because of its ability to correctly categorize susceptible and resistant isolates while minimizing categorical errors.
Isavuconazole Concentration in Real-World Practice: Consistency with Results from Clinical Trials
Authors: Andes David , Kovanda Laura , Desai A. , Kitt Therese , Zhao M. , Walsh Thomas J.
Published: May 2018

Clinical use of voriconazole, posaconazole, and itraconazole revealed the need for therapeutic drug monitoring (TDM) of plasma concentrations of these antifungal agents. This need for TDM was not evident from clinical trials. In order to establish whether this requirement also applies to isavuconazole, we examined the plasma concentrations of 283 samples from patients receiving isavuconazole in clinical practice and compared the values with those from clinical trials. The concentration distributions from real-world use and clinical trials were nearly identical (>1 μg/ml in 90% of patients). These findings suggest that routine TDM may not be necessary for isavuconazole in most instances.
Helicobacter pylori Biofilm Formation Is Differentially Affected by Common Culture Conditions, and Proteins Play a Central Role in the Biofilm Matrix
Authors: Windham Ian H. , Servetas Stephanie L. , Whitmire Jeannette M. , Pletzer Daniel , Hancock Robert E. W. , Merrell D. Scott
Published: May 2018

The concept of
Helicobacter pylori
biofilm formation is relatively new. To help provide a foundation for future biofilm studies, we characterized the biofilm formation ability of a common
H. pylori
lab strain, G27. The goal of this study was to evaluate biofilm formation by G27 in response to common culture conditions and to explore the biofilm matrix. Our results indicate that while various types of growth media did not dramatically affect biofilm formation, surface selection had a significant effect on the final biofilm mass. Furthermore, enzymatic assays and confocal microscopy revealed that proteins appear to be the primary structural component of the
H. pylori
extracellular matrix; extracellular DNA (eDNA) and polysaccharides were also present but appear to play a secondary role. Finally, we found that two well-characterized antibiofilm cationic peptides differentially affected early and late-stage biofilms. Together these results provide interesting avenues for future investigations that will seek to understand
H. pylori
biofilm formation.

IMPORTANCE
The study of
H. pylori
biofilm formation is still in its infancy. As such, there is great variability in how biofilm assays are performed across labs. While several groups have begun to investigate factors that influence
H. pylori
biofilm formation, it is not yet understood how
H. pylori
biofilm formation may vary based on commonly used conditions. These inconsistencies lead to difficulties in interpretation and comparison between studies. Here, we set out to characterize biofilm formation by a commonly available lab strain, G27. Our findings provide novel insight into optimal biofilm conditions, the biofilm matrix, and possible mechanisms to block or disrupt biofilm formation.
Identification of Novel Acinetobacter baumannii Type VI Secretion System Antibacterial Effector and Immunity Pairs
Authors: Fitzsimons Timothy C. , Lewis Jessica M. , Wright Amy , Kleifeld Oded , Schittenhelm Ralf B. , Powell David , Harper Marina , Boyce John D.
Published: May 2018

The type VI secretion system (T6SS) is a macromolecular machine that delivers protein effectors into host cells and/or competing bacteria. The effectors may be delivered as noncovalently bound cargo of T6SS needle proteins (VgrG/Hcp/PAAR) or as C-terminal extensions of these proteins. Many
Acinetobacter baumannii
strains produce a T6SS, but little is known about the specific effectors or how they are delivered. In this study, we show that
A. baumannii
AB307-0294 encodes three
vgrG
loci, each containing a
vgrG
gene, a T6SS toxic effector gene, and an antitoxin/immunity gene. Each of the T6SS toxic effectors could kill
Escherichia coli
when produced in
trans
unless the cognate immunity protein was coproduced. To determine the role of each VgrG in effector delivery, we performed interbacterial competitive killing assays using
A. baumannii
AB307-0294
vgrG
mutants, together with
Acinetobacter baylyi
prey cells expressing pairs of immunity genes that protected against two toxic effectors but not a third. Using this approach, we showed that AB307-0294 produces only three T6SS toxic effectors capable of killing
A. baylyi
and that each VgrG protein is specific for the carriage of one effector. Finally, we analyzed a number of
A. baumannii
genomes and identified significant diversity in the range of encoded T6SS VgrG and effector proteins, with correlations between effector types and
A. baumannii
global clone lineages.
Characterization of Flagellum and Toxin Phase Variation in Clostridioides difficile Ribotype 012 Isolates
Authors: Anjuwon-Foster Brandon R. , Maldonado-Vazquez Natalia , Tamayo Rita
Published: May 2018

Clostridioides difficile
causes diarrheal diseases mediated in part by the secreted toxins TcdA and TcdB.
C. difficile
produces flagella that also contribute to motility and bacterial adherence to intestinal cells during infection. Flagellum expression and toxin gene expression are linked via the flagellar alternative sigma factor, SigD. Recently, we identified a flagellar switch upstream of the early flagellar biosynthesis operon that mediates phase variation of both flagellum and toxin production in
C. difficile
strain R20291. However, we were unable to detect flagellar switch inversion in
C. difficile
strain 630, a ribotype 012 strain commonly used in research labs, suggesting that the strain is phase locked. To determine whether a phase-locked flagellar switch is limited to 630 or present more broadly in ribotype 012 strains, we assessed the frequency and phenotypic outcomes of flagellar switch inversion in multiple
C. difficile
ribotype 012 isolates. The laboratory-adapted strain JIR8094, a derivative of strain 630, and six clinical and environmental isolates were all found to be phase-off, nonmotile, and attenuated for toxin production. We isolated low-frequency motile derivatives of JIR8094 with partial recovery of motility and toxin production and found that additional changes in JIR8094 impact these processes. The clinical and environmental isolates varied considerably in the frequency by which flagellar phase-on derivatives arose, and these derivatives showed fully restored motility and toxin production. Taken together, these results demonstrate heterogeneity in flagellar and toxin phase variation among
C. difficile
ribotype 012 strains and perhaps other ribotypes, which could impact disease progression and diagnosis.

IMPORTANCE
C. difficile
produces flagella that enhance bacterial motility and secretes toxins that promote diarrheal disease symptoms. Previously, we found that production of flagella and toxins is coregulated via a flippable DNA element termed the flagellar switch, which mediates the phase-variable production of these factors. Here, we evaluate multiple isolates of
C. difficile
ribotype 012 strains and find them to be primarily flagellar phase off (
flg
-off state). Some, but not all, of these isolates showed the ability to switch between
flg
-on and -off states. These findings suggest heterogeneity in the ability of
C. difficile
ribotype 012 strains to phase-vary flagellum and toxin production, which may broadly apply to pathogenic
C. difficile
.
Reduction in Percentage of Clusters of Candida albicans and Candida parapsilosis Causing Candidemia in a General Hospital in Madrid, Spain
Authors: Escribano Pilar , Sánchez-Carrillo Carlos , Muñoz Patricia , Bouza Emilio , Guinea Jesús
Published: May 2018

The presence of clusters in units with a high incidence of candidemia suggests the need for the prevention of candidemia. We analyzed the percentage of patients involved in clusters and its evolution over a large period of time in a tertiary hospital. We studied 432 patients admitted to Gregorio Marañón Hospital with candidemia caused by
Candida albicans
(
n
= 276) or
Candida parapsilosis
(
n
= 156) between January 2007 and December 2014. Incident isolates were genotyped. A cluster was defined as a group of ≥2 patients infected by an identical genotype; we considered clusters to be “tracking clusters” when the patients involved in the cluster were admitted to the same ward within a period of 24 months. The study period was split into two periods, 2007 to 2010 (period 1) and 2011 to 2014 (period 2). The number of episodes of
C. albicans
and
C. parapsilosis
candidemia (
n
= 262 versus
n
= 170, respectively), the mean incidence (1.62 versus 1.36 episodes per 1,000 admissions, respectively), and the percentage of episodes caused by clusters (overall clusters [40% versus 12%] and tracking clusters [18% versus 3%], respectively) were significantly lower in period 2 than in period 1. Linear regression analysis showed a positive correlation between the overall number of episodes of candidemia and episodes caused by clusters (
r
2
= 0.89). We found a reduction in the number of episodes of candidemia caused by
C. albicans
and
C. parapsilosis
and a decrease in the percentage of episodes caused by clusters over time. Interestingly, the reduction was accompanied by the implementation of a campaign to reduce the number of catheter-related infections.
Evaluation of Modified Two-Tiered Testing Algorithms for Lyme Disease Laboratory Diagnosis Using Well-Characterized Serum Samples
Authors: Pegalajar-Jurado Adoracion , Schriefer Martin E. , Welch Ryan J. , Couturier Marc R. , MacKenzie Tiffany , Clark Rebecca J. , Ashton Laura V. , Delorey Mark J. , Molins Claudia R.
Published: May 2018

Standard two-tiered testing (STTT) is the recommended algorithm for laboratory diagnosis of Lyme disease (LD). Several limitations are associated with STTT that include low sensitivity in the early stages of disease, as well as technical complexity and subjectivity associated with second-tier immunoblotting; therefore, modified two-tiered testing (MTTT) algorithms that utilize two sequential first-tier tests and eliminate immunoblotting have been evaluated.
Adenovirus 5 E1A-Mediated Suppression of p53 via FUBP1
Authors: Frost Jasmine Rae , Mendez Megan , Soriano Andrea Michelle , Crisostomo Leandro , Olanubi Oladunni , Radko Sandi , Pelka Peter
Published: May 2018

Far-upstream element (FUSE) binding protein 1 (FUBP1) was originally identified as a regulator of the oncogene
c-Myc
via binding to the FUSE within the
c-Myc
promoter and activating the expression of the gene. Recent studies have identified FUBP1 as a regulator of transcription, translation, and splicing via its DNA and RNA binding activities. Here we report the identification of FUBP1 as a novel binding partner of E1A. FUBP1 binds directly to E1A via the N terminus (residues 1 to 82) and conserved region 3 (residues 139 to 204) of adenovirus 5 E1A. The depletion of FUBP1 via short interfering RNAs (siRNA) reduces virus growth and drives the upregulation of the cellular stress response by activating the expression of p53-regulated genes. During infection, FUBP1 is relocalized within the nucleus, and it is recruited to viral promoters together with E1A while at the same time being lost from the FUSE upstream of the
c-Myc
promoter. The depletion of FUBP1 affects viral and cellular gene expression. Importantly, in FUBP1-depleted cells, p53-responsive genes are upregulated, p53 occupancy on target promoters is enhanced, and histone H3 lysine 9 is hyperacetylated. This is likely due to the loss of the FUBP1-mediated suppression of p53 DNA binding. We also observed that E1A stabilizes the FUBP1-p53 complex, preventing p53 promoter binding. Together, our results identify, for the first time, FUBP1 as a novel E1A binding protein that participates in aspects of viral replication and is involved in the E1A-mediated suppression of p53 function.

IMPORTANCE
Viral infection triggers innate cellular defense mechanisms that have evolved to block virus replication. To overcome this, viruses have counterevolved mechanisms that ensure that cellular defenses are either disarmed or not activated to guarantee successful replication. One of the key regulators of cellular stress is the tumor suppressor p53 that responds to a variety of cellular stress stimuli and safeguards the integrity of the genome. During infection, many viruses target the p53 pathway in order to deactivate it. Here we report that human adenovirus 5 coopts the cellular protein FUBP1 to prevent the activation of the p53 stress response pathway that would block viral replication. This finding adds to our understanding of p53 deactivation by adenovirus and highlights its importance in infection and innate immunity.
Macrophages and Dendritic Cells Are the Predominant Cells Infected in Measles in Humans
Authors: Allen Ingrid V. , McQuaid Stephen , Penalva Rosana , Ludlow Martin , Duprex W. Paul , Rima Bertus K.
Published: May 2018

We have brought together a unique collection of 23 human cases of measles infection and studied the types of cells that are infected. This work has not been done with modern technologies such as double labeling with antibodies and confocal microscopy in human cases primarily due to the fact that it is difficult to obtain the material because, fortunately, measles is fatal in only a very small fraction of infected patients. During the past decades, the receptors for measles virus have been elucidated and monkey models have been developed. We found that, in most cases, independently of whether the tissues were obtained early or later in the infection, the primary cell types that were infected were those of the immune system such as lymphocytes, macrophages, and dendritic cells. A very small number of epithelial cells were also found to be infected.