bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased relapsed rate and treatment‐related mortality contribute to improved outcomes for pediatric acute myeloid leukemia in successive clinical trials
Authors: Alexander Thomas B. , Wang Lei , Inaba Hiroto , Triplett Brandon M. , Pounds Stanley , Ribeiro Raul C. , Pui Ching‐Hon , Rubnitz Jeffrey E.
Published: May 2017

BACKGROUND

Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed.

METHODS

This study analyzed data from patients with AML who were enrolled in successive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial.

RESULTS

There were significant improvements in 5‐year overall survival (48.9% vs 71.2%; P < .0001) and event‐free survival (43.5% vs 61.8%; P = .002) from AML97 to AML02. The 5‐year cumulative incidence of early death (ED)/treatment‐related mortality (TRM) was reduced for patients treated in AML02 (18.5% vs 7.9%; P = .007). Although the overall incidence of refractory disease (6.5% vs 5.6%; P = .736) and relapse (29.3% vs 21.0%; P = .12) did not differ between the 2 studies, patients with low‐risk AML who were treated in AML02 had a reduced incidence of relapse (27.3% vs 8.8%; P = .036).

CONCLUSIONS

The improved outcomes of the AML02 trial resulted from improved disease control for low‐risk patients and overall decreased ED/TRM. These results emphasize the importance of supportive‐care measures throughout chemotherapy courses and hematopoietic cell transplantation and the value of treatment intensity for patients with low‐risk AML while underscoring the need for novel therapy, rather than increased therapy intensity, for children with high‐risk AML. Cancer 2017;123:3791–3798. © 2017 American Cancer Society
Modeling liver electrical conductivity during hypertonic injection
Authors: Castellví Quim , Sánchez‐Velázquez Patricia , Moll Xavier , Berjano Enrique , Andaluz Anna , Burdío Fernando , Bijnens Bart , Ivorra Antoni
Published: May 2017

Metastases in the liver frequently grow as scattered tumor nodules that neither can be removed by surgical resection nor focally ablated. Previously, we have proposed a novel technique based on irreversible electroporation that may be able to simultaneously treat all nodules in the liver while sparing healthy tissue. The proposed technique requires increasing the electrical conductivity of healthy liver by injecting a hypersaline solution through the portal vein. Aiming to assess the capability of increasing the global conductivity of the liver by means of hypersaline fluids, here, it is presented a mathematical model that estimates the NaCl distribution within the liver and the resulting conductivity change. The model fuses well‐established compartmental pharmacokinetic models of the organ with saline injection models used for resuscitation treatments, and it considers changes in sinusoidal blood viscosity because of the hypertonicity of the solution. Here, it is also described a pilot experimental study in pigs in which different volumes of NaCl 20% (from 100 to 200 mL) were injected through the portal vein at different flow rates (from 53 to 171 mL/minute). The in vivo conductivity results fit those obtained by the model, both quantitatively and qualitatively, being able to predict the maximum conductivity with a 14.6% average relative error. The maximum conductivity value was 0.44 second/m, which corresponds to increasing 4 times the mean basal conductivity (0.11 second/m). The results suggest that the presented model is well suited for predicting on liver conductivity changes during hypertonic saline injection.
Key parameters decision for cloud computing: Insights from a multiple game model
Authors: Wang Jiaze , Liu Anfeng , Zhang Shigeng
Published: May 2017

In service‐oriented cloud computing systems (CCSs), the aim of cloud service organizers (CSOs) is to achieve maximum profit by collecting metadata with low cost from big data reporters (BDRs) and to provide advanced services to customers at a high price. In these systems, BDRs receive payoffs by reporting metadata to CSOs and exchanging metadata with other BDRs, and customers expect to get high‐quality services at a low price. However, because the missing of a critical parameters decision model in such service‐oriented CCSs, it is difficult to measure key parameters in CCSs such as price and quality of services in the competitive market. In this paper, we propose a multiple game (MG) model to formulate the critical parameters decision process. In the MG model, there are multiple games: games among BDRs and games among CSOs under the rule of “survival of the fittest,” games between BDRs and CSOs under the rule of “the highest payoff first,” and games between customers and CSOs under the rule of “the lowest price and the highest quality of service (QoS) first.” With the proposed multiple game (MG) model, the optimal key parameters can be obtained and the Pareto‐optimal equilibrium point can be achieved. Extensive simulation results demonstrate the effectiveness and efficiency of the proposed MG model in dynamically deciding key parameters in CCSs.
Enabling Fast Pseudo‐2D NMR Spectral Acquisition for Broadband Homonuclear Decoupling: The EXACT NMR Approach
Authors: Ndukwe Ikenna E. , Shchukina Alexandra , Zorin Vadim , Cobas Carlos , Kazimierczuk Krzysztof , Butts Craig P.
Published: May 2017

Pseudo‐2D NMR spectroscopy provides a means of acquiring broadband homonuclear decoupled spectra useful for structural characterization of complex molecules. However, data points concatenated in the direct dimension in these experiments are acquired over incremented time periods—leading to long acquisition times with no sensitivity benefits due to the absence of signal averaging between scans. Herein, the concept of EXACT NMR spectroscopy (“burst” non‐uniform sampling of data points) is explored in pseudo‐2D experiments with results revealing little or no loss in spectral quality or signal intensity despite the acceleration of acquisition—up to 400 % in some cases.
The influence of climate on early and burial diagenesis of Triassic and Jurassic sandstones from the Norwegian–Danish Basin
Authors: Weibel Rikke , Olivarius Mette , Kjøller Claus , Kristensen Lars , Hjuler Morten Leth , Friis Henrik , Pedersen Per Kent , Boyce Adrian , Andersen Morten Sparre , Kamla Elina , Boldreel Lars Ole , Mathiesen Anders , Nielsen Lars Henrik
Published: May 2017

Climate changes preserved in sandstones are documented by comparing the sediment composition and early diagenetic changes in sandstones deposited during arid to semi‐arid conditions, the Skagerrak Formation, with sandstones of the Gassum Formation deposited in a humid well‐vegetated environment. The study area covers the easternmost part of the Norwegian–Danish Basin, for which the Fennoscandian Shield functioned as sediment source area. The depositional environments of the formations, their distribution and burial depths are well‐constrained, facilitating a comprehensive petrographical and geochemical study complemented by porosity and permeability measurements of cores widely distributed in the basin (1700 to 5900 m burial depth). The Skagerrak Formation had an immature composition with more abundant feldspar, rock fragments and a larger variability in the heavy mineral assemblage when compared to the Gassum Formation, which was characterized by quartz and more stable heavy minerals. The arid to semi‐arid climate led to early oxidizing conditions under which abundant iron‐oxide/hydroxide coatings formed, while the evaporative processes occasionally resulted in caliche and gypsum precipitation. Under the humid climate, kaolinite precipitated due to leaching of feldspar and mica, and the abundant organic matter caused reducing conditions, which led to other Fe‐rich phases, i.e. pyrite, Fe‐chlorite and siderite. The inherited early diagenetic pore fluids and mineral assemblage also affect the mineral changes occurring during deeper burial, so dolomite preferentially formed in the sandstones deposited in an arid environment, while ankerite characterizes sandstones deposited under humid conditions. In addition to climate‐induced burial diagenetic changes, there are also temperature‐dependent phases, such as illite and quartz cement. Despite the same sediment source area remaining active during the entire period, the sediments that reached the Norwegian–Danish Basin were immature during the arid interval, although mature during the humid period. This has implications for provenance investigations as well as diagenetic investigations of sandstone reservoir quality.
Facies and integrated sequence stratigraphy of an Epeiric Carbonate Ramp Succession: Dhruma Formation, Sultanate of Oman
Authors: Schlaich Markus , Aigner Thomas
Published: May 2017

As an example of an epeiric carbonate ramp depositional system, the world‐class outcrops of the Middle Jurassic Dhruma Formation were studied in the Oman Mountains (Sultanate of Oman). An integrated approach was followed: facies analyses were combined with quantitative sequence‐stratigraphic methods as well as bio‐ and chemostratigraphy. Depositional environments range from peritidal to lagoonal and ‘shoal‐like’ environments. A conspicuous four‐level hierarchy of cyclicity was identified. This is substantiated by facies trends and specific cycle indicators such as various types of discontinuity surfaces, biofacies changes, and a suite of quantitative‐ and semi‐quantitative sequence‐stratigraphic methods like facies stacking pattern plots, facies percentage, bed‐thickness and bio‐component diversity plots, as well as diagrams representing the environmental range and facies belt width per high‐frequency sequence. Potential reservoir facies are present in the form of peloidal and oolitic grainstones; potential baffle/seal facies as vastly extensive mudstones and marls. A transition from peritidal to low‐energy lagoonal deposits to increasingly high‐energy deposits can be observed towards the top of the Dhruma Formation representing a landward shift of the depositional environment. This study may be useful as outcrop analogue for the hydrocarbon‐bearing parts of the Dhruma in the subsurface of the Arabian Plate and for similar epeiric carbonates elsewhere.
Host‐specific effects of soil microbial filtrates prevail over those of arbuscular mycorrhizae in a fragmented landscape
Authors: Pizano Camila , Mangan Scott A. , Graham James H. , Kitajima Kaoru
Published: May 2017

Plant–soil interactions have been shown to determine plant community composition in a wide range of environments. However, how plants distinctly interact with beneficial and detrimental organisms across mosaic landscapes containing fragmented habitats is still poorly understood. We experimentally tested feedback responses between plants and soil microbial communities from adjacent habitats across a disturbance gradient within a human‐modified tropical montane landscape. In a greenhouse experiment, two components of soil microbial communities were amplified; arbuscular mycorrhizal fungi (AMF) and a filtrate excluding AMF spores from the soils of pastures (high disturbance), coffee plantations (intermediate disturbance), and forest fragments (low disturbance), using potted seedlings of 11 plant species common in these habitats (pasture grass, coffee, and nine native species). We then examined their effects on growth of these same 11 host species with reciprocal habitat inoculation. Most plant species received a similar benefit from AMF, but differed in their response to the filtrates from the three habitats. Soil filtrate from pastures had a net negative effect on plant growth, while filtrates from coffee plantations and forests had a net positive effect on plant growth. Pasture grass, coffee, and five pioneer tree species performed better with the filtrate from “away” (where these species rarely occur) compared to “home” (where these species typically occur) habitat soils, while four shade‐tolerant tree species grew similarly with filtrates from different habitats. These results suggest that pastures accumulate species‐specific soil enemies, while coffee plantations and forests accumulate beneficial soil microbes that benefit pioneer native plants and coffee, respectively. Thus, compared to AMF, soil filtrates exerted stronger habitat and host‐specific effects on plants, being more important mediators of plant–soil feedbacks across contrasting habitats.
Barcoding rotifer biodiversity in Mediterranean ponds using diapausing egg banks
Authors: Moreno Emilio , Conde‐Porcuna José M. , Gómez Africa
Published: May 2017

The biodiversity of Mediterranean freshwater bodies is among the most threatened worldwide; therefore, its accurate estimation is an urgent issue. However, traditional methods are likely to underestimate freshwater zooplankton biodiversity due to its high species seasonality and cryptic diversity. We test the value of applying DNA barcoding to diapausing egg banks, in combination with the creation of a reference collection of DNA barcodes using adult individual samples, to characterize rotifer communities. We use monogonont rotifers from two lakes in Doñana National Park and one from Ruidera Natural Park in Spain as models to create a reference collection of DNA barcodes for taxonomically diagnosed adult individuals sampled from the water column, to compare with the sequences obtained from individual eggs from the diapausing egg banks. We apply two different approaches to carry out DNA taxonomy analyses, the generalized mixed Yule coalescent method (GMYC) and the Automatic Barcode Gap Discovery (ABGD), to the obtained sequences and to publicly available rotifer sequences. We obtained a total of 210 new rotifer COI sequences from all three locations (151 diapausing eggs and 59 adults). Both GMYC and ABGD generated the same 35 operational taxonomic units (OTUs), revealing four potential cryptic species. Most sequences obtained from diapausing eggs (85%) clustered with sequences obtained from morphologically diagnosed adults. Our approach, based on a single sediment sample, retrieved estimates of rotifer biodiversity higher than or similar to those of previous studies based on a number of seasonal samples. This study shows that DNA barcoding of diapausing egg banks is an effective aid to characterize rotifer diversity in Mediterranean freshwater bodies.
Exploring the effects of fishing pressure and upwelling intensity over subtidal kelp forest communities in Central Chile
Authors: Pérez‐Matus Alejandro , Carrasco Sergio A. , Gelcich Stefan , Fernandez Miriam , Wieters Evie A.
Published: May 2017

Understanding the processes that drive kelp forest communities is critical for management and conservation of these productive ecosystems. As a way to advance in this direction, we explored the effects of fishing pressure and upwelling intensity over kelp forest communities along the central coast of Chile. We sampled kelp communities in different upwelling conditions associated with contrasting management regimes, namely Territorial User Rights for Fisheries (TURFs) and open‐access (OA) areas. In TURF areas, we found a 2.6‐fold increase in reef fish biomass, higher diversity of all fish trophic groups, mainly dominated by benthic carnivore feeders, and a 1.8‐fold reduction in the number of kelp grazers. On the other hand, upwelling regimes evidence a 1.6‐fold increase in abundance and recruitment of the dominant kelp (Lessonia trabeculata), and also an increase in biomass of planktivorous reef fishes. We found that grazers were capable of reducing kelp condition (measured as canopy foliage index) in OA areas outside the influence of upwelling. Enclosure experiments in the field revealed the effect of grazers on kelps, reducing kelp growth (i.e., blade elongation) and increasing blade tissue loss. Results provide evidence that TURF areas could be important ancillary conservation instruments in kelp forest ecosystems, if key processes of the subtidal community assemblages (e.g., interactions between grazers and reef fish) are maintained. We conclude that human impact interplays with the influence of upwelling in structuring kelp communities.
Population, habitat, and marine location effects on early marine survival and behavior of Puget Sound steelhead smolts
Authors: Moore Megan E. , Berejikian Barry A.
Published: May 2017

Steelhead trout (Onchorhynchus mykiss) smolts suffer high mortality rates during their rapid migration through the Salish Sea. Among‐population variability in mortality rates may reflect (1) genetic fitness variation among populations, (2) freshwater environmental effects on fish condition, or (3) differences in local marine conditions upon seawater entry. A reciprocal transplant experiment was conducted to separate the influence of freshwater effects (combined effects of population and freshwater environment) from effects of local marine conditions on survival of two Puget Sound steelhead populations. Steelhead smolts from the Green River in Central Puget Sound (urbanized and hatchery‐influenced) and the Nisqually River in South Puget Sound (less urbanized; no hatchery influence) were tagged with acoustic telemetry transmitters and released back into their natal river or transported and released into the other river. Population of origin had little influence on probability of surviving the migration through Puget Sound. However, smolts released into the Green River had higher survival through Puget Sound (17%) than smolts released into the Nisqually River (6%); the extra 64‐km migration segment for the Nisqually‐released fish accounted for most of the difference between the two release locations. Neither fork length nor translocation influenced survival, though release date did affect survival of Nisqually population smolts regardless of their release location. Residence time and behavior in the two estuaries were similar, and no effects of population of origin or release date were evident. Marine travel rates also did not differ between populations, release dates, or release locations. This study indicates that mortality occurring in the Salish Sea is likely driven by processes in inland marine environments, more so than intrinsic effects of population or freshwater‐rearing environments.
A Zwitterionic Gold(I) Diphenylphosphane Oxide Complex Stabilized by a Hard Pulling Lewis Acid and a Soft Pushing Lewis Base
Authors: Kather Ralf , Lork Enno , Beckmann Jens
Published: May 2017

The reaction of Ph2P(O)H with B(C6F5)3 provided the Lewis pair complex Ph2(H)POB(C6F5)3 (5) containing a bipolar +P–O–B– linkage. The reaction of 5 with [(tht)AuCl] (tht = tetrahydrothiophene) proceeded with elimination of HCl and formation of [{(C6F5)3BOPPh2}Au(tht)] (6), which can be regarded as push–pull complex between a zwitterionic OPPh2Au unit and a hard Lewis acid, B(C6F5)3, coordinating at the oxygen atom, and a soft Lewis base, tht, coordinating at the gold atom.
First Asymmetric Total Synthesis and Insight into the Structure of Laurenidificin
Authors: Yoshikawa Yusuke , Yamakawa Maki , Kobayashi Tetsuya , Murai Kenichi , Arisawa Mitsuhiro , Sumimoto Michinori , Fujioka Hiromichi
Published: May 2017

(+)‐Laurenidificin has a fused bis‐THF skeleton and an enyne structure in its side chain. It is known that the bis‐THF skeleton is cis,cis fused, and the absolute configuration at the C6 position is R, but the whole structure has not been determined. We synthesized one possible isomer of (+)‐laurenidificin by using intramolecular double bromoetherification as a key step. Treatment of a protected (E,E)‐diene diol with 2,4,4,6‐tetrabromo‐2,5‐cyclohexadienone as the halogenating agent afforded a cis,cis‐fused bis‐THF derivative in good yield with high stereoselectivity. Several additional transformations, including introduction of a hydroxy group at the C6 position and construction of the enyne structure, gave a possible isomer of (+)‐laurenidificin. The 1H NMR and 13C NMR spectroscopy data of this isomer are in complete agreement with those of natural (+)‐laurenidificin, and its optical rotation and that of natural laurenidificin have the same positive sign.
Diindenocorannulenes: Curved Aromatics Blending Bowl‐in‐Bowl Assembly and Nanocarbon Material Properties
Authors: Tian Xiaoqi , Roch Loïc M. , Baldridge Kim K. , Siegel Jay S.
Published: May 2017

Directed synthesis, X‐ray crystal structures, computational analysis, and characterization of dimethyldiindenocorannulene (15), cyclooctenodiindenocorannulene (16), and N‐heptyldiindenocorannulenemaleimide (17) motivate a model for curved aromatics, blending bowl‐in‐bowl assemblies with nanocarbon material properties.
Female sexual pain: Epidemiology and genetic overlap with chronic widespread pain
Authors: Burri A. , Ogata S. , Williams F.
Published: May 2017

Background

Increased tender spots and lowered general pain thresholds have been observed in patients with dyspareunia. Based on this, the aim of the study was to compare the co‐occurrence of female sexual pain across various pain populations and to further explore the aetiological structure underlying sexual pain by dissecting the genetic and environmental covariation among sexual pain, chronic widespread pain (CWP) and the previously reported psychological correlates of anxiety sensitivity and depression.

Methods

A multivariate twin study including 1489 female twin individuals (246 full MZ pairs, 187 full DZ pairs and 623 whose co‐twin did not participate). Main outcomes measures included self‐reported diagnosis of osteoarthritis and rheumatoid arthritis, and validated questionnaires for the assessment of sexual pain, CWP, depression and anxiety sensitivity.

Results

Sexual pain showed a small but statistically significant correlation with CWP (r = 0.08; p < 0.05), anxiety sensitivity (r = 0.15, p < 0.001) and depression (r = 0.09, p < 0.01). The heritability of sexual pain was found to be 31%. Multivariate variance component analysis revealed a genetic factor common among CWP, depression, anxiety sensitivity and sexual pain, and a second genetic factor shared between anxiety sensitivity and sexual pain only. We further detected genetic and environmental factors unique to sexual pain, explaining 24.01% and 67.24%, respectively, of the phenotypic variance.

Conclusions

Our findings suggest some overlap between sexual pain and CWP and point towards a shared but complex psychophysiological aetiology underlying sexual pain. Results further highlight the influence of specific environmental and contextual stressors in the development and maintenance of sexual pain.

Significance

Sexual pain shares a common genetic aetiology with chronic widespread pain and the frequently reported psychological comorbidities of depression and anxiety. Overall this suggests a complex psychophysiological aetiology underlying chronic pain conditions. The high proportion of variance in sexual pain explained by environmental factors further highlights the importance of specific environmental and contextual stressors in the development and maintenance of the condition.
Quantification of carbamylated albumin in serum based on capillary electrophoresis
Authors: Delanghe Sigurd , Moerman Alena , Pletinck Anneleen , Schepers Eva , Glorieux Griet , Van Biesen Wim , Delanghe Joris R. , Speeckaert Marijn M.
Published: May 2017

Protein carbamylation, a nonenzymatic posttranslational modification promoted during uremia, is linked to a poor prognosis. In the present study, carbamylation of serum albumin was assayed using the symmetry factor on a capillary electrophoresis instrument (Helena V8). The symmetry factor has been defined as the distance from the center line of the peak to the back slope, divided by the distance from the center line of the peak to the front slope, with all measurements made at 10% of the maximum peak height. Serum albumin, creatinine, and urea concentrations were assayed using routine methods, whereas uremic toxins were determined using HPLC. In vitro carbamylation induced a marked albumin peak asymmetry. Reference values for the albumin symmetry factor were 0.69–0.92. In kidney patients, albumin peak asymmetry corresponded to the chronic kidney disease stage (p < 0.0001). The symmetry factor correlated well with serum urea (r = −0.5595, p < 0.0001) and creatinine (r = −0.5986, p < 0.0001) concentrations. Several protein‐bound uremic toxins showed a significant negative correlation with the symmetry factor. Morphology of the albumin fraction was not affected by presence of glycated albumin and protein‐bound antibiotics. In conclusion, the presented method provides a simple, practical way for monitoring protein carbamylation.
Genotoxicity testing approaches for the safety assessment of substances used in food contact materials prior to their authorization in the European Union
Authors: Bolognesi Claudia , Castoldi Anna F. , Crebelli Riccardo , Barthélémy Eric , Maurici Daniela , Wölfle Detlef , Volk Katharina , Castle Laurence
Published: May 2017

Food contact materials are all materials and articles intended to come directly or indirectly into contact with food. Before being included in the positive European “Union list” of authorized substances (monomers, other starting substances and additives) for plastic food contact materials, the European Food Safety Authority (EFSA) must assess their safety “in use”. If relevant for risk, the safety of the main impurities, reaction and degradation products originating from the manufacturing process is also evaluated. Information on genotoxicity is always required irrespective of the extent of migration and the resulting human exposure, in view of the theoretical lack of threshold for genotoxic events. The 2008 EFSA approach, requiring the testing of food contact materials in three in vitro mutagenicity tests, though still acceptable, is now superseded by the 2011 EFSA Scientific Committee's recommendation for only two complementary tests including a bacterial gene mutation test and an in vitro micronucleus test, to detect two main genetic endpoints (i.e., gene mutations and chromosome aberrations). Follow‐up of in vitro positive results depends on the type of genetic effect and on the substance's systemic availability. In this study, we provide an analysis of the data on genotoxicity testing gathered by EFSA on food contact materials for the period 1992–2015. We also illustrate practical examples of the approaches that EFSA took when evaluating “non standard” food contact chemicals (e.g., polymeric additives, oligomer or other reaction mixtures, and nanosubstances). Additionally, EFSA's experience gained from using non testing methods and/or future possibilities in this area are discussed. Environ. Mol. Mutagen. 58:361–374, 2017. © 2017 Wiley Periodicals, Inc.
Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood
Authors: Solomon Olivia , Yousefi Paul , Huen Karen , Gunier Robert B. , Escudero‐Fung Maria , Barcellos Lisa F. , Eskenazi Brenda , Holland Nina
Published: May 2017

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Phthalates are known endocrine disruptors with ubiquitous exposures in the general population including pregnant women, and they have been linked with a number of adverse health outcomes. We examined the association between in utero phthalate exposure and altered patterns of cord blood DNA methylation in 336 Mexican‐American newborns. Concentrations of 11 phthalate metabolites were analyzed in maternal urine samples collected at 13 and 26 weeks gestation as a measure of fetal exposure. DNA methylation was assessed using the Infinium HumanMethylation 450K BeadChip adjusting for cord blood cell composition. To identify differentially methylated regions (DMRs) that may be more informative than individual CpG sites, we used two different approaches, DMRcate and comb‐p. Regional assessment by both methods identified 27 distinct DMRs, the majority of which were in relation to multiple phthalate metabolites. Most of the significant DMRs (67%) were observed for later pregnancy (26 weeks gestation). Further, 51% of the significant DMRs were associated with the di‐(2‐ethylhexyl) phthalate metabolites. Five individual CpG sites were associated with phthalate metabolite concentrations after multiple comparisons adjustment (FDR), all showing hypermethylation. Genes with DMRs were involved in inflammatory response (IRAK4 and ESM1), cancer (BRCA1 and LASP1), endocrine function (CNPY1), and male fertility (IFT140, TESC, and PRDM8). These results on differential DNA methylation in newborns with prenatal phthalate exposure provide new insights and targets to explore mechanism of adverse effects of phthalates on human health. Environ. Mol. Mutagen. 58:398–410, 2017. © 2017 Wiley Periodicals, Inc.
Association of cytochrome P450 1B1 haplotypes with head and neck cancer risk
Authors: Katiyar Tridiv , Maurya Shailendra S. , Hasan Feza , Singh Arvind P. , Khan Anwar J. , Hadi Rahat , Singh Sudhir , Bhatt Madan L.B. , Parmar Devendra
Published: May 2017

Genetic polymorphisms have been reported in several cytochrome P450 (CYP) genes, including CYP1B1 which metabolically activates procarcinogens present in tobacco to carcinogenic intermediates. This study used a case–control approach in North Indian population to determine associations between genetic variants in CYP1B1 and risk of Head and Neck Squamous Cell Carcinoma (HNSCC). We examined the genotype and haplotype frequencies at various single‐nucleotide polymorphisms (SNPs), including SNPs previously reported in the promoter region and intron 1 of CYP1B1 in Caucasians. Using cycle sequencing, 9 SNPs were identified in the promoter region, intron 1, and exons 2 and 3. Haplotype analysis revealed that 5 SNPs (those in the promoter region, intron, and Arg48Gly and Ala119Ser in exon 2) were in strong linkage disequilibrium (LD). Cases with the T–A–T–G–T haplotype were significantly associated with increased risk of HNSCC. Interestingly, qRT‐PCR studies revealed a significant increase in mRNA expression of CYP1B1 in peripheral blood isolated from cases with the T–A–T–G–T haplotype compared with cases with the C–G–C–C–G haplotype, and in cases compared to controls for both main haplotypes. The data thus provide evidence that CYP1B1 haplotypes could be more effective in predicting HNSCC risk. Environ. Mol. Mutagen. 58:443–450, 2017. © 2017 Wiley Periodicals, Inc.
Poly(vinyl chloride) and its fire properties
Authors: Hirschler Marcelo M.
Published: May 2017

This work provides an up‐to‐date review of the fire properties of poly(vinyl chloride) (PVC) materials, both rigid (unplasticized) and flexible (plasticized). The fire properties addressed include ignitability, ease of extinction (oxygen index), flame spread (small scale and intermediate scale), heat release, smoke obscuration, smoke toxicity, hydrogen chloride emission and decay, and performance in real‐scale fires.

This comprehensive review includes a wide selection of references and tables illustrating the properties of PVC materials in comparison with those of other polymeric materials, including, in many instances, wood materials. The work puts these fire properties in perspective, showing that the heat release rate (the key fire property) of rigid PVC (and that of properly flame‐retarded flexible PVC) are among the lower values found for combustible materials. This work also shows that the smoke toxicity and smoke obscuration resulting from burning PVC materials in real‐scale fires is in the same range as those of other materials.
Improving watershed management practices in humid regions
Authors: Zimale Fasikaw A. , Tilahun Seifu A. , Tebebu Tigist Y. , Guzman Christian D. , Hoang Linh , Schneiderman Elliot M. , Langendoen Eddy J. , Steenhuis Tammo S.
Published: May 2017

In many parts of the world, watershed management practices have been extremely effective. However, implementation of soil and water conservation technologies in the humid African highlands, while beneficial in the short term, were remarkably unsuccessful in the long term. Insights from community knowledge perspectives have revealed that alternative methods are needed. Although conservation practices are designed to conserve water in semi‐arid areas, safely draining excess water is needed in humid areas. The objective of this paper is to review current watershed management approaches used in humid regions as exemplified by those used in Ethiopian highlands and then based on these findings propose more effective practices. Although current government sponsored practices primarily protect the hillsides, direct run‐off is generated from areas that become saturated on valley bottoms near rivers and on specific parts of the hillsides with degraded soils (or with highly permeable surface soils) and with perched water tables on slowly permeable horizons at shallow depths. In these areas, direct run‐off is increasing with deforestation and the soil degradation, demanding additional drainage ways that evolve in the form of gullies. Therefore, watershed management interventions for erosion control should prioritize revegetation of degraded areas, increasing sustainable infiltration, and rehabilitating gullies situated at saturated bottomlands.
Factors associated with oophorectomy in children with benign ovarian masses
Authors: Kapp Daniel S. , Rosenfeld Emily B. , Chan Joshua E. , Chan John K.
Published: May 2017

Age, surgical route, hospital location, and socioeconomic status were associated with undergoing oophorectomy in children with benign ovarian masses.
Some results on cyclic interval edge colorings of graphs
Authors: Asratian Armen S. , Casselgren Carl Johan , Petrosyan Petros A.
Published: May 2017

A proper edge coloring of a graph G with colors is called a cyclic interval t‐coloring if for each vertex v of G the edges incident to v are colored by consecutive colors, under the condition that color 1 is considered as consecutive to color t. We prove that a bipartite graph G of even maximum degree admits a cyclic interval ‐coloring if for every vertex v the degree satisfies either or . We also prove that every Eulerian bipartite graph G with maximum degree at most eight has a cyclic interval coloring. Some results are obtained for ‐biregular graphs, that is, bipartite graphs with the vertices in one part all having degree a and the vertices in the other part all having degree b; it has been conjectured that all these have cyclic interval colorings. We show that all (4, 7)‐biregular graphs as well as all ‐biregular () graphs have cyclic interval colorings. Finally, we prove that all complete multipartite graphs admit cyclic interval colorings; this proves a conjecture of Petrosyan and Mkhitaryan.
Exploring the radiosynthesis and in vitro characteristics of [68Ga]Ga‐DOTA‐Siglec‐9
Authors: Jensen Svend B. , Käkelä Meeri , Jødal Lars , Moisio Olli , Alstrup Aage K.O. , Jalkanen Sirpa , Roivainen Anne
Published: May 2017

Vascular adhesion protein 1 is a leukocyte homing‐associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283–297 of sialic acid‐binding IgG‐like lectin 9 (Siglec‐9) “CARLSLSWRGLTLCPSK” bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([68Ga]Ga‐DOTA‐Siglec‐9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [68Ga]Ga‐DOTA‐Siglec‐9 are presented and compared with previously published methods. A simple, robust radiosynthesis of [68Ga]Ga‐DOTA‐Siglec‐9 with a yield of 62% (non decay‐corrected) was identified, and it had a radiochemical purity >98% and a specific radioactivity of 35 MBq/nmol. Furthermore, the protein binding and stability of [68Ga]Ga‐DOTA‐Siglec‐9 were analyzed in vitro in mouse, rat, rabbit, pig, and human plasma and compared with in vivo pig results. The plasma in vitro protein binding of [68Ga]Ga‐DOTA‐Siglec‐9 was the lowest in the pig followed by rabbit, human, rat, and mouse. It was considerably higher in the in vivo pig experiments. The in vivo stability in pigs was lower than the in vitro stability. Despite considerable species differences, the observed characteristics of [68Ga]Ga‐DOTA‐Siglec‐9 are suitable as a positron emission tomography tracer.
Parsing disease‐relevant protein modifications from epiphenomena: perspective on the structural basis of SOD1‐mediated ALS
Authors: Schmitt N. D. , Agar J. N.
Published: May 2017

Conformational change and modification of proteins are involved in many cellular functions. However, they can also have adverse effects that are implicated in numerous diseases. How structural change promotes disease is generally not well‐understood. This perspective illustrates how mass spectrometry (MS), followed by toxicological and epidemiological validation, can discover disease‐relevant structural changes and therapeutic strategies. We (with our collaborators) set out to characterize the structural and toxic consequences of disease‐associated mutations and post‐translational modifications (PTMs) of the cytosolic antioxidant protein Cu/Zn‐superoxide dismutase (SOD1). Previous genetic studies discovered >180 different mutations in the SOD1 gene that caused familial (inherited) amyotrophic lateral sclerosis (fALS). Using hydrogen–deuterium exchange with mass spectrometry, we determined that diverse disease‐associated SOD1 mutations cause a common structural defect – perturbation of the SOD1 electrostatic loop. X‐ray crystallographic studies had demonstrated that this leads to protein aggregation through a specific interaction between the electrostatic loop and an exposed beta‐barrel edge strand. Using epidemiology methods, we then determined that decreased SOD1 stability and increased protein aggregation are powerful risk factors for fALS progression, with a combined hazard ratio > 300 (for comparison, a lifetime of smoking is associated with a hazard ratio of ~15 for lung cancer). The resulting structural model of fALS etiology supported the hypothesis that some sporadic ALS (sALS, ~80% of ALS is not associated with a gene defect) could be caused by post‐translational protein modification of wild‐type SOD1. We developed immunocapture antibodies and high sensitivity top‐down MS methods and characterized PTMs of wild‐type SOD1 using human tissue samples. Using global hydrogen–deuterium exchange, X‐ray crystallography and neurotoxicology, we then characterized toxic and protective subsets of SOD1 PTMs. To cap this perspective, we present proof‐of‐concept that post‐translational modification can cause disease. We show that numerous mutations (N➔D; Q➔E), which result in the same chemical structure as the PTM deamidation, cause multiple diseases. Copyright © 2017 John Wiley & Sons, Ltd.
Leukemia/lymphoma‐related factor (LRF) exhibits stage‐ and context‐dependent transcriptional controls in the oligodendrocyte lineage and modulates remyelination
Authors: Davidson Nathan L. , Yu Fengshan , Kijpaisalratana Naruchorn , Le Tuan Q. , Beer Laurel A. , Radomski Kryslaine L. , Armstrong Regina C.
Published: May 2017

Leukemia/lymphoma‐related factor (LRF), a zinc‐finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored. This study is the first to examine the role of LRF in CNS pathology. We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically relevant lesion characteristics. LRF was rarely expressed in oligodendrocyte progenitors (OP) yet, was detected in nuclei of the majority of oligodendrocytes in healthy adult CNS and during remyelination. Plp/CreERT:Zbtb7afl/fl mice were then used with cuprizone demyelination to determine the effect of LRF knockdown on oligodendrocyte repopulation and remyelination. Cuprizone was given for 6 weeks to demyelinate the corpus callosum. Tamoxifen was administered at 4, 5, or 6 weeks after the start of cuprizone. Tamoxifen‐induced knockdown of LRF impaired remyelination during 3 or 6‐week recovery periods after cuprizone. LRF knockdown earlier within the oligodendrocyte lineage using NG2CreERT:Zbtb7afl/fl mice reduced myelination after 6 weeks of cuprizone. LRF knockdown from either the Plp/CreERT line or the NG2CreERT line did not significantly change OP or oligodendrocyte populations. In vitro promoter assays demonstrated the potential for LRF to regulate transcription of myelin‐related genes and the notch target Hes5, which has been implicated in control of myelin formation and repair. In summary, in the oligodendrocyte lineage, LRF is expressed mainly in oligodendrocytes but is not required for oligodendrocyte repopulation of demyelinated lesions. Furthermore, LRF can modulate the extent of remyelination, potentially by contributing to interactions regulating transcription.
Assessing meta‐regression methods for examining moderator relationships with dependent effect sizes: AMonteCarlo simulation
Authors: López‐López José Antonio , Van den Noortgate Wim , Tanner‐Smith Emily E. , Wilson Sandra Jo , Lipsey Mark W.
Published: May 2017

Dependent effect sizes are ubiquitous in meta‐analysis. Using Monte Carlo simulation, we compared the performance of 2 methods for meta‐regression with dependent effect sizes—robust variance estimation (RVE) and 3‐level modeling—with the standard meta‐analytic method for independent effect sizes. We further compared bias‐reduced linearization and jackknife estimators as small‐sample adjustments for RVE and Wald‐type and likelihood ratio tests for 3‐level models. The bias in the slope estimates, width of the confidence intervals around those estimates, and empirical type I error and statistical power rates of the hypothesis tests from these different methods were compared for mixed‐effects meta‐regression analysis with one moderator either at the study or at the effect size level. All methods yielded nearly unbiased slope estimates under most scenarios, but as expected, the standard method ignoring dependency provided inflated type I error rates when testing the significance of the moderators. Robust variance estimation methods yielded not only the best results in terms of type I error rate but also the widest confidence intervals and the lowest power rates, especially when using the jackknife adjustments. Three‐level models showed a promising performance with a moderate to large number of studies, especially with the likelihood ratio test, and yielded narrower confidence intervals around the slope and higher power rates than those obtained with the RVE approach. All methods performed better when the moderator was at the effect size level, the number of studies was moderate to large, and the between‐studies variance was small. Our results can help meta‐analysts deal with dependency in their data.
Enhanced charge generation in doped organic/organic p–n heterojunction for improving the performance of tandem organic light emitting diode
Authors: Qin Dashan , Zhao Wei , Chen Li , Shi Zhihua , Cao Huan
Published: May 2017

The doped organic/organic p–n heterojunctions have been applied as charge generation structure (CGS) in tandem organic light emitting diodes (TOLEDs). It is found that the field‐induced charge generation takes place more efficiently at the interface between Li2CO3 n‐doped bathocuproine (BCP:Li2CO3) and MoO3 p‐doped 4,4′‐N,N′‐dicarbazole‐biphenyl (CBP:MoO3) than at the interface between BCP:Li2CO3 and MoO3 p‐doped 4,4‐bis[N‐1‐naphthyl‐N‐phenylamino]biphenyl (NPB:MoO3). It is because the process of electrons tunneling through the depletion zone from the highest occupied molecular orbit (HOMO) of CBP:MoO3 to the lowest unoccupied molecular orbit (LUMO) of BCP:Li2CO3 is more efficient than that from the HOMO of NPB:MoO3 to the LUMO of BCP:Li2CO3. Compared to the TOLED using the conventional CGS of 10‐nm BCP:Li2CO3/20‐nm NPB:MoO3, the one using the CGS of 10‐nm BCP:Li2CO3/10‐nm CBP:MoO3/10‐nm NPB:MoO3 shows increased device performance. In addition, the interconnecting property of CGS of 10‐nm BCP:Li2CO3/x nm CBP:MoO3/20 − x nm NPB:MoO3 shows a strong dependence on the thickness of CBP:MoO3. We provide a new insight on optimizing Ohmic loss in the CGSs, useful for improving the performance of TOLEDs.
Abnormal Fetal Findings Associated With a Global Sphericity Index of the 4‐Chamber View Below the 5th Centile
Authors: DeVore Greggory R. , Satou Gary , Sklansky Mark
Published: May 2017

Objectives

The purpose of this study was to evaluate the global sphericity index (GSI) of the 4‐chamber view and correlate the results with abnormal ultrasound findings.

Methods

The epicardial end‐diastolic basal‐apical length (BAL) and transverse length (TL) of the 4‐chamber view were measured to compute the GSI (BAL/TL) in 200 control fetuses between 20 and 40 weeks' gestation. Three hundred study fetuses were prospectively examined between 17 and 39 weeks' gestation. The GSI, Z score, and centile were computed for each of the fetuses.

Results

The GSI (1.233; SD, 0.0953) in the control fetuses was independent of gestational age. Eighteen percent of the study fetuses (55 of 300) had a GSI below the 5th centile (<1.08), of whom 96% (53 of 55) had additional abnormal ultrasound findings. Fetuses with an estimated fetal weight below the 10th centile had a significantly (P < .05) higher rate of an umbilical artery Doppler pulsatility index above the 95th centile (27% versus 17.7%), a middle cerebral artery Doppler pulsatility index below the 5th centile (27% versus 0%), an abnormal cerebroplacental ratio (27% versus 4.5%), and an amniotic fluid index of less than 5 cm (36% versus 9%). The TL was significantly increased compared with the BAL in fetuses with cardiac dysfunction, irrespective of the estimated fetal weight.

Conclusions

An abnormal GSI below the 5th centile is associated with abnormal fetal ultrasound findings.
Disparities in health in the United States: An overview of the social determinants of health for otolaryngologists
Authors: Bergmark Regan W. , Sedaghat Ahmad R.
Published: May 2017

Objectives

Social determinants of health include social and demographic factors such as poverty, education status, race and ethnicity, gender, insurance status, and other factors that influence (1) development of illness, (2) ability to obtain and utilize healthcare, and (3) health and healthcare outcomes. In otolaryngology, as in other subspecialty surgical fields, we are constantly confronted by patients’ social and demographic circumstances including poverty, language barriers, and lack of health insurance and yet there is limited research on how these factors impact health equity in our field, or how attention to these patient characteristics may improve health equity. This review provides the reader with a framework to understand the social determinants of health including how socioeconomic status, insurance status, race, gender, and other factors impact health.

Data Sources and Review Methods

Foundational papers on the social determinants of health are reviewed, as well as otolaryngology publications focused on health and healthcare disparities.

Results

The social determinants of health have a major impact on patient health as well as healthcare utilization, but there is a relative lack of data on these factors and how they can be addressed within otolaryngology. Incorporating tools to measure social and demographic characteristics and actually report on these measures is a first simple step to increase the data on the social determinants of health as they pertain to otolaryngology.

Conclusion

More research is needed on the social determinants of health, and how they impact otolaryngic disease. Medicare's Accountable Care Organization models will increasingly change the way in which physicians are reimbursed, making the social determinants of health central not only to our moral conscience but also the bottom line.

Level of Evidence

4