bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics and Safety Profile of Artesunate-Amodiaquine Coadministered with Antiretroviral Therapy in Malaria-Uninfected HIV-Positive Malawian Adults
Authors: Banda Clifford G. , Dzinjalamala Fraction , Mukaka Mavuto , Mallewa Jane , Maiden Victor , Terlouw Dianne J. , Lalloo David G. , Khoo Saye H. , Mwapasa Victor
Published: May 2018

There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus-infected (HIV
+
) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared the area under the concentration-time curve from 0 to 28 days (AUC
0–28
) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV
+
adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy. In step 1, malaria-uninfected adults (
n
= 6/arm) received half the standard adult treatment regimen of artesunate-amodiaquine. In step 2, another cohort (
n
= 25/arm) received the full regimen. In step 1, there were no safety signals or significant differences in desethylamodiaquine AUC
0–28
among participants in the ritonavir-boosted lopinavir, nevirapine, and antiretroviral therapy-naive arms. In step 2, compared with those in the antiretroviral therapy-naive arm, participants in the ritonavir-boosted lopinavir arm had 51% lower desethylamodiaquine AUC
0–28
, with the following geometric means (95% confidence intervals [CIs]): 23,822 (17,458 to 32,506) versus 48,617 (40,787 to 57,950) ng · h/ml (
P
< 0.001). No significant differences in AUC
0–28
were observed between nevirapine and antiretroviral therapy-naive arms. Treatment-emergent transaminitis was higher in the nevirapine (20% [5/25]) than the antiretroviral therapy-naive (0.0% [0/25]) arm (risk difference, 20% [95% CI, 4.3 to 35.7];
P
= 0.018). The ritonavir-boosted lopinavir antiretroviral regimen was associated with reduced desethylamodiaquine exposure, which may compromise artesunate-amodiaquine's efficacy. Coadministration of nevirapine and artesunate-amodiaquine may be associated with hepatoxicity.
Comparison of the QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube Interferon Gamma Release Assays in Patients at Risk for Tuberculosis and in Health Care Workers
Authors: Theel Elitza S. , Hilgart Heather , Breen-Lyles Margaret , McCoy Kevin , Flury Rhiannon , Breeher Laura E. , Wilson John , Sia Irene G. , Whitaker Jennifer A. , Clain Jeremy , Aksamit Timothy R. , Escalante Patricio
Published: May 2018

The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI;
n
= 39) or active TB infection (
n
= 3), and in health care workers (HCWs;
n
= 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients [
R
] > 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.
Common and Distinct Capsid and Surface Protein Requirements for Secretion of Complete and Genome-Free Hepatitis B Virions
Authors: Ning Xiaojun , Luckenbaugh Laurie , Liu Kuancheng , Bruss Volker , Sureau Camille , Hu Jianming
Published: May 2018

During the morphogenesis of hepatitis B virus (HBV), an enveloped virus, two types of virions are secreted: (i) a minor population of complete virions containing a mature nucleocapsid with the characteristic, partially double-stranded, relaxed circular DNA genome and (ii) a major population containing an empty capsid with no DNA or RNA (empty virions). Secretion of both types of virions requires interactions between the HBV capsid or core protein (HBc) and the viral surface or envelope proteins. We have studied the requirements from both HBc and envelope proteins for empty virion secretion in comparison with those for secretion of complete virions. Substitutions within the N-terminal domain of HBc that block secretion of DNA-containing virions reduced but did not prevent secretion of empty virions. The HBc C-terminal domain was not essential for empty virion secretion. Among the three viral envelope proteins, the smallest, S, alone was sufficient for empty virion secretion at a basal level. The largest protein, L, essential for complete virion secretion, was not required but could stimulate empty virion secretion. Also, substitutions in L that eliminated secretion of complete virions reduced but did not eliminate empty virion secretion. S mutations that blocked secretion of the hepatitis D virus (HDV), an HBV satellite, did not block secretion of either empty or complete HBV virions. Together, these results indicate that both common and distinct signals on empty capsids and mature nucleocapsids interact with the S and L proteins during the formation of complete and empty virions.

IMPORTANCE
Hepatitis B virus (HBV) is a major cause of severe liver diseases, including cirrhosis and cancer. In addition to the complete infectious virion particle, which contains an outer envelope layer and an interior capsid that, in turn, encloses a DNA genome, HBV-infected cells also secrete noninfectious, incomplete viral particles in large excess over the number of complete virions. In particular, the empty (or genome-free) virion shares with the complete virion the outer envelope and interior capsid but contains no genome. We have carried out a comparative study on the capsid and envelope requirements for the secretion of these two types of virion particles and uncovered both shared and distinct determinants on the capsid and envelope for their secretion. These results provide new information on HBV morphogenesis and have implications for efforts to develop empty HBV virions as novel biomarkers and a new generation of HBV vaccine.
Expression Levels of Glycoprotein O (gO) Vary between Strains of Human Cytomegalovirus, Influencing the Assembly of gH/gL Complexes and Virion Infectivity
Authors: Zhang Le , Zhou Momei , Stanton Richard , Kamil Jeremy , Ryckman Brent J.
Published: May 2018

The tropism of human cytomegalovirus (HCMV) is influenced by the envelope glycoprotein complexes gH/gL/gO and gH/gL/UL128-131. During virion assembly, gO and the UL128-131 proteins compete for binding to gH/gL in the endoplasmic reticulum (ER). This assembly process clearly differs among strains, since Merlin (ME) virions contain abundant gH/gL/UL128-131 and little gH/gL/gO, whereas TR contains much higher levels of total gH/gL, mostly in the form of gH/gL/gO, but much lower levels of gH/gL/UL128-131 than ME. Remaining questions include (i) what are the mechanisms behind these assembly differences, and (ii) do differences reflect
in vitro
culture adaptations or natural genetic variations? Since the UL74(gO) open reading frame (ORF) differs in 25% of amino acids between TR and ME, we analyzed recombinant viruses in which the UL74(gO) ORF was swapped. TR virions were >40-fold more infectious than ME. Transcriptional repression of UL128-131 enhanced the infectivity of ME to the level of TR, despite still far lower levels of gH/gL/gO. Swapping the UL74(gO) ORF had no effect on either TR or ME. A quantitative immunoprecipitation approach revealed that gH/gL expression levels were within 4-fold between TR and ME, but the gO expression level was 20-fold lower for ME, which suggested differences in mRNA transcription, translation, or rapid ER-associated degradation of gO.
trans
-Complementation of gO expression during ME replication gave a 6-fold enhancement of infectivity beyond the 40-fold effect of UL128-131 repression alone. Overall, strain variations in the assembly of gH/gL complexes result from differences in the expression of gO and UL128-131, and selective advantages for reduced UL128-131 expression during fibroblast propagation are much stronger than those for higher gO expression.

IMPORTANCE
Specific genetic differences between independently isolated HCMV strains may result from purifying selection on
de novo
mutations arising during propagation in culture or random sampling among the diversity of genotypes present in clinical specimens. Results presented indicate that while reduced UL128-131 expression may confer a powerful selective advantage during cell-free propagation of HCMV in fibroblast cultures, selective pressures for increased gO expression are much weaker. Thus, variation in gO expression among independent strains may represent natural genotype variability present
in vivo
. This may have important implications for virus-host interactions, such as immune recognition, and underscores the value of studying molecular mechanisms of replication using multiple HCMV strains.
Basic lifestyle advice to individuals at high risk of type 2 diabetes: a 2-year population-based diabetes prevention study. The DE-PLAN intervention in the HUNT Study, Norway
Authors: Jølle Anne , Åsvold Bjørn Olav , Holmen Jostein , Carlsen Sven Magnus , Tuomilehto Jaakko , Bjørngaard Johan Håkon , Midthjell Kristian
Published: May 2018

Objective

Among individuals at high risk for diabetes identified through a population survey, we performed an intervention study with basic lifestyle advice aiming to prevent diabetes.

Research design and methods

Among 50 806 participants in the HUNT3 Survey (2006–2008), 5297 individuals with Finnish Diabetes Risc Score (FINDRISC ≥15 were invited to an oral glucose tolerance test (OGTT) and an education session with lifestyle advice, and 2634 (49.7%) attended. Among them, 2380 people without diabetes were included in the prevention study with repeated examinations and education sessions after 6, 12, and 24 months. We examined participation, diabetes incidence, glycemia, and adiposity during follow-up.

Results

Of 2380 participants, 1212 (50.9%) participated in ≥3 of the four examinations. Diabetes was detected in 3.5%, 3.1%, and 4.0% of individuals at the 6-month, 12-month, and 24-month examinations, respectively, indicating a 10.3% 2-year diabetes incidence. Mean (95% CI) increases from baseline to 2-year follow-up were 0.30 (0.29 to 0.32) percentage points (3.3 (3.2 to 3.5) mmol/mol) for Hemoglobin A1c, 0.13 (0.10 to 0.16) mmol/L for fasting serum-glucose, 0.46 (0.36 to 0.56) mmol/L for 2-hour OGTT s-glucose, 0.30 (0.19 to 0.40) kg/m2forbody mass index (BMI) (all p<0.001) and −0.5 (-0.9 to −0.2) cm for waist circumference (p=0.004), with broadly similar estimates by baseline age, sex, education, depressive symptoms, BMI, physical activity, and family history of diabetes. Only 206 (8.7%) participants had evidence of >5% weight loss during follow-up; their fasting and 2-hour s-glucose did not increase, and HbA1cincreased less than in other participants.

Conclusion

Basic lifestyle advice given to high-risk individuals during three group sessions with 6-month intervals was not effective in reducing 2-year diabetes risk.
Potential impact of introducing the pneumococcal conjugate vaccine into national immunisation programmes: an economic-epidemiological analysis using data from India
Authors: Megiddo Itamar , Klein Eili , Laxminarayan Ramanan
Published: May 2018

Pneumococcal pneumonia causes an estimated 105 000 child deaths in India annually. The planned introduction of the serotype-based pneumococcal conjugate vaccine (PCV) is expected to avert child deaths, but the high cost of PCV relative to current vaccines provided under the Universal Immunization Programme has been a concern. Cost-effectiveness studies from high-income countries are not readily comparable because of differences in the distribution of prevalent serotypes, population and health systems. We extended IndiaSim, our agent-based simulation model representative of the Indian population and health system, to model the dynamics ofStreptococcus pneumoniae. This enabled us to evaluate serotype and overall disease dynamics in the context of the local population and health system, an aspect that is missing in prospective evaluations of the vaccine. We estimate that PCV13 introduction would cost approximately US$240 million and avert US$48.7 million in out-of-pocket expenditures and 34 800 (95% CI 29 600 to 40 800) deaths annually assuming coverage levels and distribution similar to DPT (diphtheria, pertussis and tetanus) vaccination (~77%). Introducing the vaccine protects the population, especially the poorest wealth quintile, from potentially catastrophic expenditure. The net-present value of predicted money-metric value of insurance for 20 years of vaccination is US$160 000 (95% CI US$151 000 to US$168 000) per 100 000 under-fives, and almost half of this protection is for the bottom wealth quintile (US$78 000; 95% CI 70 800 to 84 400). Extending vaccination to 90% coverage averts additional lives and provides additional financial risk protection. Our estimates are sensitive to immunity parameters in our model; however, our assumptions are conservative, and if willingness to pay per years of life lost averted is US$228 or greater, then introducing the vaccine is more cost-effective than our baseline (no vaccination) in more than 95% of simulations.
Prevalence estimates and risk factors for early childhood wheeze across Europe: the EuroPrevall birth cohort
Authors: Selby Anna , Munro Alasdair , Grimshaw Kate E , Cornelius Victoria , Keil Thomas , Grabenhenrich Linus , Clausen Michael , Dubakiene Ruta , Fiocchi Alessandro , Kowalski Marek L , Papadopoulos Nikolaos G , Reche Marta , Sigurdardottir Sigurveig T , Sprikkelman Aline B , Xepapadaki Paraskevi , Mills E N Clare , Beyer Kirsten , Roberts Graham
Published: May 2018

Background

Preschool wheeze is an important problem worldwide. No comparative population-based studies covering different countries have previously been undertaken.

Objective

To assess the prevalence of early childhood wheeze across Europe and evaluate risk factors focusing on food allergy, breast feeding and smoke exposure.

Methods

Infants from nine countries were recruited into the EuroPrevall birth cohort. At 12 and 24 months, data on wheeze, allergic signs/symptoms, feeding, smoke exposure, infections and day care attendance were collected using questionnaires. Poisson regression was used to assess risk factors for wheeze.

Results

12 049 infants were recruited. Data from the second year of life were available in 8805 (73.1%). The prevalence of wheeze in the second year of life ranged from <2% in Lodz (Poland) and Vilnius (Lithuania) to 13.1% (95% CI 10.7% to 15.5%) in Southampton (UK) and 17.2% (95% CI 15.0% 19.5%) in Reykjavik (Iceland). In multivariable analysis, frequent lower respiratory tract infections in the first and second years of life (incidence rate ratio (IRR) 1.9 (95% CI 1.3 to 2.6) and 2.5 (95% CI 1.9 to3.4), respectively), postnatal maternal smoking (IRR 1.6, 95% CI 1.1 to 2.4), day care attendance (IRR 1.6, 95% CI 1.1 to 2.5) and male gender (IRR 1.3, 95% CI 1.0 to 1.7) were associated with wheeze. The strength of their association with wheeze differed between countries. Food allergy and breast feeding were not independently associated with wheeze.

Conclusion

The prevalence of early childhood wheeze varied considerably across Europe. Lower respiratory tract infections, day care attendance, postnatal smoke exposure and male gender are important risk factors. Further research is needed to identify additional modifiable risk factors that may differ between countries.
Diagnosis of Caroli syndrome in a crossbreed dog
Authors: Serrano Gonçalo , Mortier Femke , Bosseler Leslie , Taylor Olivia , Paepe Dominique
Published: May 2018

This case report describes Caroli syndrome in a young dog, which presented with fever, icterus, acute vomiting, weight loss, hyporexia and lethargy. Two days after hospital admission, the development of severe ascites prompted the use of abdominal CT, which revealed the presence of a thickened gall bladder wall with dilation of the intrahepatic and common bile ducts, intrahepatic bile duct sacculation, and acquired extrahepatic portosystemic shunts. Exploratory coeliotomy revealed a gall bladder mucocoele with tortuous bile ducts. The owners opted not to follow further treatment and elected for euthanasia. This case highlights an unusual cause of hepatic and posthepatic icterus, which should be included in the differential diagnosis list of a young dog presenting with icterus.
Mechanical properties of single crystal copper ellipsoidal nanoshells by molecular dynamics
Authors: Yang Qinyou , Yang Zailin , Yang Yong , Zhang Guowei , Zhang Yu
Published: May 2018

Single crystal copper ellipsoidal nanoshells under outer normal tensile loadings are investigated by the molecular dynamics method. Normal stress and Mises stress are introduced to describe the mechanical properties. The uniform thickness nanoshells, the variable thickness nanoshells and the variable radius nanoshells are simulated to elucidate the effect of thickness on yielding behaviors and other mechanical properties. Potential energies, stresses and dislocations of nanoshells are discussed in the paper. The dislocations of these nanoshells form an octagon or that with an external quadrangle. The variable thickness nanoshells break this shape slightly. The potential energies of nanoshells have stable stages and then increase. The outer normal stresses and Mises stresses of different models differ from eath other. The thickness of nanoshells affects the elastic stage and the variable thickness nanoshell has different mechanical properties with others. When the radiuses of nanoshells with the same thickness are different, their dislocation shapes are the pressed octagon. Thier normal yield stresses are different, but their Mises yield stress are same. Also, the outer shape determines the trend of curves. The structure of a sphere is steadier than that of an ellipsoid.
Reduction of Ceiling Fan Noise by Serrated Trailing Edge
Authors: Lee Hsiao Mun , Lim Kian Meng , Lee Heow Pueh
Published: May 2018

Six ceiling fan blade models with different types of trailing edge serrations were created and were simulated using commercial software in the present studies in order to investigate the effectiveness of various trailing edge serrations in reducing fan blade trailing edge noise. They were original, flat tip, serrated, rectangular, half flat tip and half rectangular half flat tip fan blades. The simulation results showed that the half flat tip fan blade had the best acoustical performance where it could obtain an overall noise reduction of 13.9[Formula: see text]dBA followed by rectangular fan blade with 10.9[Formula: see text]dBA, flat tip fan blade with 9.2[Formula: see text]dBA, half rectangular half flat tip fan blade with 5.0[Formula: see text]dBA and serrated fan blade with 4.7[Formula: see text]dBA. The effectiveness of TE serrations in reducing trailing edge noise was also proven through experimental testing in an anechoic chamber in the present studies.
An interactive design method for realistic fruit rot modeling and simulation
Authors: Wu Sheng , Xiao Boxiang , Miao Teng , Wen Weiliang , Guo Xinyu
Published: May 2018

This paper presents a general 3D method to simulate a rotting process in fruits using a visual model for the digital design of the fruits. The global rot parameter and rot resistance parameter are used to control a dynamic simulation of a rotting process. The rot resistance parameters of every point of a 3D fruit model are generated by an interactive designing method that is similar to the traditional sketch drawing tools. We construct a texture of a rot region on a fruit surface by resistance parameters. The degree of rot that is used to control both shape and appearance of rotten fruit surface can be computed by tuning the resistance parameters and global rot parameters. We derive an exponential function to calculate the depression displacement of geometric shape caused by the rot. In order to render a wrinkle on the rot region, we use a normal noise map to modify a normal vector of fruit model and use an isotropic ward BRDF model to represent an appearance of fruit in which the time-varying diffuse reflectance is derived from the real photos. We utilize a linear function to control the dynamic simulation processes including shape deformation and aging appearance. We have evaluated our method by simulating the rotten apple and moldy orange. The results have shown that our method provides a dynamic, real-time and realistic simulation, and it is flexible, fast and of a general character for digital fruit design as a visualization model.
KurSL: Model of Anharmonic Coupled Oscillations Based on Kuramoto Coupling and Sturm–Liouville Problem
Authors: Laszuk Dawid , Cadenas Jose O. , Nasuto Slawomir J.
Published: May 2018

Physiological signaling is often oscillatory and shows nonlinearity due to complex interactions of underlying processes or signal propagation delays. This is particularly evident in case of brain activity which is subject to various feedback loop interactions between different brain structures, that coordinate their activity to support normal function. In order to understand such signaling in health and disease, methods are needed that can deal with such complex oscillatory phenomena. In this paper, a data-driven method for analyzing anharmonic oscillations is introduced. The KurSL model incorporates two well-studied components, which in the past have been used separately to analyze oscillatory behavior. The Sturm–Liouville equations describe a form of a general oscillation, and the Kuramoto coupling model represents a set of oscillators interacting in the phase domain. Integration of these components provides a flexible framework for capturing complex interactions of oscillatory processes of more general form than the most commonly used harmonic oscillators. The paper introduces a mathematical framework of the KurSL model and analyzes its behavior for a variety of parameter ranges. The significance of the model follows from its ability to provide information about coupled oscillators’ phase dynamics directly from the time series. KurSL offers a novel framework for analyzing a wide range of complex oscillatory behaviors, such as the ones encountered in physiological signals.
Calculation of the Six-Beam Diffraction in Layered Media Using Polynomials of Principal Minors
Authors: Belyayev Yuriy N.
Published: May 2018

The scattering of plane elastic waves by an anisotropic layered medium in the case of the six-beam diffraction is considered. The matrix method for solving wave equations is developed. The conversion coefficients [Formula: see text] for the three types of incident waves (horizontally polarized shear wave, vertically polarized shear wave and longitudinal wave) are defined. Representations of coefficients [Formula: see text] through elements of transfer matrix are found. The method for coefficients [Formula: see text] calculations is presented. It does not require the solving of algebraic problem on eigenvalues for waves in an anisotropic layer. Some features of the functional dependencies of [Formula: see text] on the angles of incidence, wave frequency and layer thickness are demonstrated on several examples of the crystals in a three-layer model. It is shown that the conversions SH wave into SV waves and SV wave into SH waves are equivalent.
Response of soil C- and O-horizon and terrestrial moss samples to various lithological units and mineralization in southern Norway
Authors: Flem Belinda , Torgersen Espen , Englmaier Peter , Andersson Malin , Finne Tor E. , Eggen Ola , Reimann Clemens
Published: May 2018

This study was conducted to determine which sample material provides the most reliable signal for geochemical exploration under Norwegian conditions. A 100-km long transect was placed over two mineral deposits in southern Norway; the Nordli Mo deposit with surfaces exposure of molybdenite (MoS
2
) and a sandstone-hosted Pb mineralization with surface exposures of sphalerite. At each of 41 sampling sites, soil C- and O-horizon samples and terrestrial moss (
Hylocomium splendens
) were collected. All samples were analysed for 53 chemical elements following an aqua regia extraction. The Pb deposit is indicated by all three sample materials by anomalous high consentratons of Pb, especially by the C-horizon. The Mo deposit is indicated by more than one anomalous high Mo value in both O- and C-horizon but is not indicated by any clear anomaly in moss. The general mineraliation area of the two deposits is detected on a regional scale using low sample density. However, to exactly localise the mineralization and to define drill targets, a sample density >10 sites/km
2
would be required. Though high Pb concentrations in moss are usually interpreted as being due to anthropogenic activities, results presented here demonstrate that locally moss reacts strongly to the presence of Pb mineralization.

Supplementary material:
South-north transect plots of all elements are provided as a PDF. A Google Earth file showing the analytical results of moss, O- and C horizon at all sample sites in addition to topographical details is available. All data are also downloadable as an Excel file. All are available at
https://doi.org/10.6084/m9.figshare.c.4082981
Catchment-scale heterogeneity of flow and storage properties in a weathered/fractured hard rock aquifer from resistivity and magnetic resonance surveys: implications for groundwater flow paths and the distribution of residence times
Authors: Comte J.-C. , Ofterdinger U. , Legchenko A. , Caulfield J. , Cassidy R. , Mézquita González J. A.
Published: May 2018

Groundwater pathways and residence times are controlled by aquifer flow and storage properties, which, in weathered/fractured hard rock aquifers, are characterized by high spatial heterogeneity. Building on earlier work in a metamorphic aquifer in NW Ireland, new clay mineralogy and analyses of geophysical data provided high spatial resolution constraints on the variations in aquifer properties. Groundwater storage values derived from magnetic resonance sounding and electrical resistivity tomography were found to largely vary laterally and with depth, by orders of magnitude. The subsequent implementation of hillslope, two-dimensional numerical groundwater models showed that incorporating heterogeneity from geophysical data in model parametrization led to the best fit to observations compared with a reference model based on borehole data alone. Model simulations further revealed that (1) strong spatial heterogeneity produces deeper, longer groundwater flow paths and higher age mixing, in agreement with the mixed sub-modern/modern ages (mostly <50 years) provided by independent tritium data, and (2) areas with extensive weathering/fracturing are correlated with seepage zones of older groundwater resulting from changes in the flow directions and are likely to act as drainage structures for younger groundwater on a catchment or regional scale. Implications for groundwater resilience to climate extremes and surface pollution are discussed together with recommendations for further research.
Intraocular pressure and cardiovascular alterations investigated in artificial gravity as a countermeasure to spaceflight associated neuro-ocular syndrome
Authors: Anderson Allison P. , Butterfield Joseph S. , Subramanian Prem S. , Clark Torin K.
Published: May 2018

Artificial gravity (AG) has been proposed as a countermeasure to spaceflight-associated neuro-ocular syndrome (SANS). The etiology of SANS is unknown but mimicking gravitational loading through AG may mitigate these negative adaptations. Seventeen subjects (nine men, eight women; 18–32 yr) were analyzed in four experimental conditions: 1) standing, 2) supine, 3) AG with the center of rotation at the eye (AGEC), and 4) AG with 2 Gs at the feet (AG2G). In both AG conditions, subjects were spun to produce 1 G at their center of mass. Data included self-administered intraocular pressure (IOP, Tono-pen AVIA, Depew, NY), heart rate (HR), and mean arterial blood pressure (MAP, Omron Series 10, Omron Healthcare, Kyoto, Japan). Data were analyzed with repeated measures ANOVAs with Tukey-Kramer corrections for multiple pairwise comparisons. IOP was 15.7 ± 1.4 mmHg (mean ± 95% confidence interval) standing, 18.8 ± 1.3 mmHg supine, 18.5 ± 1.7 mmHg in AGEC, and 17.5 ± 1.5 mmHg in AG2G. Postures showed a main effect [F(3,48) = 11.0, P < 0.0005], with standing significantly lower than supine ( P = 0.0009), AGEC ( P = 0.002), and AG2G (0.036). Supine, AGEC, and AG2G were not statistically different. HR and MAP were lower in supine compared with all other postures ( P = 0.002 to P < 0.0005), but there were no differences between standing, AGEC, and AG2G. IOP in supine and standing was consistent with previous studies, but contrary to our hypothesis, remained elevated in both AG conditions. Cardiovascular parameters and hydrostatic gradients determine IOP, which remain unchanged compared with standing. These results suggest additional influence on IOP from previously unconsidered factors.

NEW & NOTEWORTHY This is the first study, to the authors’ knowledge, to measure intraocular pressure in short-radius centrifuge artificial gravity (AG), which has been proposed as a countermeasure to the spaceflight-associated neuro-ocular syndrome (SANS). If the etiology of SANS is related to intraocular pressure, these results have implications for whether or not short-radius AG can be used to prevent ocular changes relevant to it. Our results indicate this proposed countermeasure merits further investigation.
The Bohr/Haldane effect: a model-based uncovering of the full extent of its impact on O2delivery to and CO2removal from tissues
Authors: Malte Hans , Lykkeboe Gunnar
Published: May 2018

For a century, the influence of the Bohr effect on the utilization of blood-borne oxygen has been deemed secondary to its influence on the uptake of carbon dioxide by the blood. Here, we show that the opposite is the case. Using a simple two-ligand, two-state formulation, we modeled the simultaneous oxygen and proton binding to hemoglobin, as well as the resulting acid-base changes of the surrounding solution. Blocking of the Bohr effect in this model system results in a dramatic increase in the oxygen affinity, as expressed by the oxygen partial pressure at half saturation, the P50. It also becomes clear that the P50and the Bohr factor (a measure of the size of the Bohr effect) are not independent but directly related. Thus, everything else being equal, varying the number of Bohr groups from 0 to 8 per tetramer results in an increase in the Bohr factor from 0 to −0.9 and an increase in P50from 6 to 46 mmHg at a constant Pco2of 40 mmHg. Therefore, changes in hemoglobin structure that lead to changes in the Bohr factor will inevitably also change hemoglobin oxygen affinity.

NEW & NOTEWORTHY Using a mathematical model, we show that the Bohr effect has a more profound effect on gas exchange than is evident when comparing oxygen equilibrium curves measured in the laboratory at different constant values of Pco2or pH. Protons preloaded on the Bohr groups, as well as the protons taken up during oxygen unloading, dramatically decrease oxygen affinity of the physiological oxygen equilibrium curve. Therefore, the Bohr effect is instrumental in setting the oxygen affinity.
Acute Liver Failure among Patients on Efavirenz-Based Antiretroviral Therapy
Authors: Segamwenge Innocent Lule , Bernard Miriam Kaunanele
Published: May 2018

Objectives. To describe the clinical characteristics of patients presenting with fulminant liver failure after varying periods of exposure to Efavirenz containing antiretroviral medications. Methods. We report a series of 4 patients with human immunodeficiency virus (HIV) infection who were admitted with acute liver failure (ALF) over a 6-month period. All these patients had been treated with a range of Efavirenz containing antiretroviral regimens and were negative for hepatitis A, B, and C infections as well as other opportunistic infections, all were negative for autoimmune hepatitis, and none had evidence of chronic liver disease or use of alcohol or herbal medications. Information on patient clinical characteristics, current antiretroviral regimen, CD4 count, HIV-1 RNA levels, and clinical chemistry parameters was collected. Informed consent was provided. Results. During a 6-month period, four patients without other known risk factors for acute hepatitis presented with symptomatic drug-induced liver injury with varying symptoms and outcomes. The pattern of liver injury was hepatocellular for all the 4 cases. Liver biopsies were done for all the four cases and the results showed a heavy mixed inflammatory cell infiltrate with eosinophils. For three patients withdrawal of Efavirenz from their antiretroviral regimen was sufficient to restore transaminase levels to normal and led to improvement of clinical symptoms. For one patient his clinical course was characterized by fulminant liver failure and fluctuating episodes of hepatic encephalopathy which ultimately resulted in his death. Conclusion. Hepatotoxicity of Efavirenz is not as rare as previously described in the literature and does actually present with fatal outcomes. The key message to note is that frequent monitoring of liver enzymes should be done at initiation of antiretroviral therapy and should continue throughout the treatment period.
Ascites in a Young Woman: A Rare Presentation of Eosinophilic Gastroenteritis
Authors: Santos Carina , Morgado Francisco , Blanco Celestina , Parreira João , Costa João , Rodrigues Lara , Marfull Luís , Cardoso Patrícia
Published: May 2018

Introduction. Eosinophilic gastroenteritis (EGE) is a rare idiopathic disease that can affect one or more organs of the digestive tract. It has an estimated incidence of 1–20 cases per 100,000 patients. Klein et al. classified EGE into 3 subtypes: predominant mucosal, muscular, or subserosal. Clinical Case. We report a case of a 32-year-old woman, who presented with diffuse abdominal pain, nausea, postprandial infarction, diarrhea, and moderate ascites of three-week evolution. The rest of physical examination did not show alterations. The past medical history was unremarkable. Laboratory test results revealed peripheral blood eosinophilia. Abdominal CT scan revealed diffuse and concentric parietal thickening of the distal 2/3 of esophagus, moderate volume ascites, and small bowel wall thickening and distension on the left quadrants. The paracentesis revealed 93.3% of eosinophils. The colon biopsies evidenced an increase in the number of eosinophils. Secondary causes of eosinophilia were excluded. The patient was treated with oral prednisolone 40 mg/day with immediate clinical and analytical improvement. Conclusion. Eosinophilic gastroenteritis is a rare condition with a nonspecific and highly variable clinical presentation, which requires a high level of clinical suspicion. It is a diagnosis of exclusion. Secondary causes of eosinophilia such as intestinal tuberculosis, parasitosis, and malignant neoplasms should be excluded.
Patch Based Collaborative Representation with Gabor Feature and Measurement Matrix for Face Recognition
Authors: Xu Zhengyuan , Liu Yu , Ye Mingquan , Huang Lei , Yu Hao , Chen Xun
Published: May 2018

In recent years, sparse representation based classification (SRC) has emerged as a popular technique in face recognition. Traditional SRC focuses on the role of the l1-norm but ignores the impact of collaborative representation (CR), which employs all the training examples over all the classes to represent a test sample. Due to issues like expression, illumination, pose, and small sample size, face recognition still remains as a challenging problem. In this paper, we proposed a patch based collaborative representation method for face recognition via Gabor feature and measurement matrix. Using patch based collaborative representation, this method can solve the problem of the lack of accuracy for the linear representation of the small sample size. Compared with holistic features, the multiscale and multidirection Gabor feature shows more robustness. The usage of measurement matrix can reduce large data volume caused by Gabor feature. The experimental results on several popular face databases including Extended Yale B, CMU_PIE, and LFW indicated that the proposed method is more competitive in robustness and accuracy than conventional SR and CR based methods.
Reanalysis of Ωc→Ξc+K- Decay in QCD
Authors: Aliev T. M. , Bilmis S. , Savci M.
Published: May 2018

The strong coupling constants of newly observed Ωc0 baryons with spins J=1/2 and J=3/2 decaying into Ξc+K- are estimated within light cone QCD sum rules. The calculations are performed within two different scenarios on quantum numbers of Ωc baryons: (a) all newly observed Ωc baryons are negative parity baryons; that is, the Ωc(3000), Ωc(3050), Ωc(3066), and Ωc(3090) have quantum numbers JP=1/2- and JP=3/2- states, respectively; (b) the states Ωc(3000) and Ωc(3050) have quantum numbers JP=1/2- and JP=1/2+, while the states Ωc(3066) and Ωc(3090) have the quantum numbers JP=3/2- and JP=3/2+, respectively. By using the obtained results on the coupling constants, we calculate the decay widths of the corresponding decay. The results on decay widths are compared with the experimental data of LHC Collaboration. We found out that the predictions on decay widths within these scenarios are considerably different from the experimental data; that is, both considered scenarios are ruled out.
Protective Role of Antioxidant Huskless Barley Extracts on TNF‐α‐Induced Endothelial Dysfunction in Human Vascular Endothelial Cells
Authors: Liao Zhanghua , Cai Haoran , Xu Zekun , Wang Jing , Qiu Chen , Xie Jing , Huang Wuyang , Sui Zhongquan
Published: May 2018

Oxidative stress and inflammation are considered as two key factors that contribute to the development of atherosclerosis. This study was to investigate the antioxidant capacity of huskless barley and to explore its protective functions through the regulation of the antioxidant defense and inflammatory response in human umbilical vein endothelial cells (HUVEC). The oxygen radical absorbance capacity (ORAC), ferric‐reducing antioxidant power (FRAP), and 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS) scavenging capacity of water and alkali extracts of the polysaccharides from nine huskless barley varieties were investigated in vitro. The antioxidant properties of the alkaline extracts were more pronounced than those of the water extracts. The results from the cell model showed that pretreatment of HUVEC with the water or alkaline extracts of the polysaccharides from the huskless barley cultivars QHH and NLGL decreased the levels of reactive oxygen species (ROS), monocyte chemotactic protein 1 (MCP‐1), and vascular cell adhesion molecule 1 (VCAM‐1) but increased the level of superoxide dismutase (SOD) and maintained cell viability. Huskless barley polysaccharide extracts exhibited the vasodilatory effect of inhibiting angiotensin‐converting enzyme (ACE) production. These discoveries revealed the potent protective functions of barley in oxidative damage and a potential role for barley in preventing chronic inflammation in cardiovascular diseases.
Semiempirical Efficiency Calibration in Semiconductor HPGe Gamma-Ray Spectroscopy
Authors: Krneta Nikolić Jelena , Rajačić Milica , Todorović Dragana , Janković Marija , Sarap Nataša , Pantelić Gordana , Vukanac Ivana
Published: May 2018

One of the main problems in quantitative gamma-ray spectroscopy is the determination of detection efficiency, for different energies, source-detector geometries, and composition of samples or sources. There are, in principle, three approaches to this issue: experimental, numerical, and semiempirical. Semiempirical approach is based on the calculation of the efficiency for the measured sample on the basis of an experimental efficiency measured on the same detector, but with a calibration source that can be of different size, geometry, density, or composition—the so-called efficiency transfer. The aim of this paper is to analyze the semiempirical approach, using EFFTRAN and MEFFTRAN software as a typical example. These software were used in the Department of Radiation and Environmental Protection, Vinča Institute of Nuclear Sciences, on three HPGe detectors. The results were compared to the experimentally obtained efficiency, and further validation is performed by measuring reference materials issued within the framework of several interlaboratory intercomparisons. The analysis of the results showed that the efficiency transfer produces good results with the discrepancies within the limits of the measurement uncertainty. Also, for intercomparison measurement, utest criterion for the trueness of the result was applied showing that the majority of the obtained results were acceptable. Some difficulties were identified, and the ways to overcome them were discussed.
Unexpected Exacerbation of Tracheal Stenosis in a Patient with Hunter Syndrome Undergoing Cardiac Surgery
Authors: Terabe Nobue , Yamashita Soichiro , Tanaka Makoto
Published: May 2018

We report unexpected exacerbation of tracheal stenosis during general anesthesia in a 50-year-old patient with Hunter syndrome undergoing cardiac surgery for valvular disease. He had undergone cervical laminoplasty 3 months previously; at that time, his airway had been uneventfully managed. Preoperative flexible fiberoptic laryngoscopy showed a normal upper respiratory tract, but chest computed tomography showed tracheal stenosis that had flattened the lumen. The narrowest part above the tracheal bifurcation was 2 cm long and the anteroposterior diameter was ≤6 mm. Cardiac surgery was uneventfully performed. After weaning from cardiopulmonary bypass, the tidal volume suddenly decreased from 450 to 120 ml at sternal closure. The end-expiratory carbon dioxide pressure increased from 39 to 71 mmHg. Bronchoscopic examination showed that the part of tracheal bifurcation was almost occluded. A tidal volume of 400 ml was obtained after the transesophageal echocardiography probe was removed and the peak inspiratory pressure increased. Although extubation was performed on the second postoperative day, procaterol inhalation and noninvasive positive-pressure ventilation were needed for 3 days because of wheezing and dyspnea. In conclusion, the risk of lower respiratory tract obstruction should be considered during general anesthesia in patients with Hunter syndrome with collapsible tracheal stenosis undergoing cardiac surgery.
An Analytical Method for Jack-Up Riser’s Fatigue Life Estimation
Authors: Wang Fengde , Xiao Wensheng , Liu Qi , Wu Lei , Meng Zhanbin
Published: May 2018

In order to determine whether a special sea area and its sea state are available for the jack-up riser with surface blowout preventers, an analytical method is presented to estimate the jack-up riser’s wave loading fatigue life in this study. In addition, an approximate formula is derived to compute the random wave force spectrum of the small-scale structures. The results show that the response of jack-up riser is a narrow band random vibration. The infinite water depth dispersion relation between wavenumber and wave frequency can be used to calculate the wave force spectrum of small-scale structures. The riser’s response mainly consists of the additional displacement response. The fatigue life obtained by the formula proposed by Steinberg is less than that of the Bendat method.
Overexpression of TRIM24 Stimulates Proliferation and Glucose Metabolism of Head and Neck Squamous Cell Carcinoma
Authors: Wang Hongming , Xue Weishuang , Jiang Xuejun
Published: May 2018

TRIM24 (Tripartite Motif Containing 24) is a recently identified oncogene overexpressed in various cancers. However, the molecular mechanism of TRIM24 in the progression of head and neck squamous cell carcinoma (HNSCC) remains ambiguous. In the present study, we analyzed the expression pattern of TRIM24 in 100 HNSCC tissues and found that TRIM24 was overexpressed in 43/100 HNSCC cases. Significant association was found between TRIM24 overexpression and tumor-node-metastasis (TNM) stage (p=0.0034) and T stage (p=0.0048). Furthermore, we overexpressed and knocked down TRIM24 in Detroit 562 and FaDu cell lines, respectively. TRIM24 overexpression promoted proliferation, colony formation, and invasion, while TRIM24 depletion inhibited proliferation, colony formation, and invasion. Further studies showed that TRIM24 facilitated cell cycle transition and upregulated cyclin D1 and p-Rb. In addition, we found that GLUT3, a key protein involved in regulating glucose metabolism, was altered in HNSCC cells overexpressing TRIM24. We demonstrated that TRIM24 overexpression increased glucose uptake ATP production. Overexpression of TRIM24 increases cell sensitivity to glucose deprivation in Detroit cells. Depleting TRIM24 in FaDu cells demonstrated the opposite results. We also showed that TRIM24 could bind to the promoter region of cyclin D1. In conclusion, TRIM24 is upregulated in HNSCC and promotes HNSCC cell growth and invasion through modulation of cell cycle, glucose metabolism, and GLUT3, making TRIM24 a potential oncoprotein in HNSCC.
A Prospective Evaluation of Two Rapid Phenotypical Antimicrobial Susceptibility Technologies for the Diagnostic Stewardship of Sepsis
Authors: Giordano Cesira , Piccoli Elena , Brucculeri Veronica , Barnini Simona
Published: May 2018

Rapid identification of bloodstream pathogens by MALDI-TOF MS and the recently introduced rapid antimicrobial susceptibility testing (rAST) directly from positive blood cultures allow clinicians to promptly achieve a targeted therapy, especially for multidrug resistant microorganisms. In the present study, we propose a comparison between phenotypical rASTs performed in light-scattering technology (Alfred 60AST, Alifax®) and fluorescencein situhybridization (Pheno™, Accelerate) directly from positive blood cultures, providing results in 4–7 hours. Blood samples from 67 patients admitted to the Azienda Ospedaliero-Universitaria Pisana were analyzed. After the direct MALDI-TOF MS identification, the rAST was performed at the same time both on Alfred 60AST and Pheno. Alfred 60AST provided qualitative results, interpreted in terms of clinical categories (SIR). Pheno provided identification and MIC values for each antibiotic tested. Results were compared to the broth microdilution assay (SensiTitre™, Thermo Fisher Scientific), according to EUCAST rules. Using Alfred 60AST, an agreement was reached, 91.1% for Gram-negative and 95.7% for Gram-positive bacteria, while using Pheno, the agreement was 90.6% for Gram-negative and 100% for Gram-positive bacteria. Both methods provided reliable results; Alfred 60AST combined with MALDI-TOF MS proved itself faster and cheaper. Pheno provided identification and MIC determination in a single test and, although more expensive, may be useful whenever MIC value is necessary and where MALDI-TOF MS is not present.