bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of the Impact of Cytochrome P450 2C9 Genotypes on the Drug–Drug Interaction Potential of Siponimod With Physiologically‐Based Pharmacokinetic Modeling: A Comprehensive Approach for Drug Label Recommendations
Authors: Huth Felix , Gardin Anne , Umehara Kenichi , He Handan
Published: June 2019

We predicted the drug–drug interaction (DDI) potential of siponimod in presence of cytochrome P450 (CYP)2C9/CYP3A4 inhibitors/inducers in subjects with different CYP2C9 genotypes by physiologically‐based pharmacokinetic (PK) modeling. The model was established using in vitro and clinical PK data and verified by adequately predicting siponimod PK when coadministered with rifampin. With strong and moderate CYP3A4 inhibitors, an increased DDI risk for siponimod was predicted for CYP2C9*3/*3 genotype vs. other genotypes area under the curve ratio (AUCR): 3.03–4.20 vs. ≤ 1.49 for strong; 2.42 vs. 1.14–1.30 for moderate. AUCRs increased with moderate (2.13–2.49) and weak (1.12–1.42) CYP3A4/CYP2C9 inhibitors to the same extent for all genotypes. With strong CYP3A4/moderate CYP2C9 inducers and moderate CYP3A4 inducers, predicted AUCRs were 0.21–0.32 and 0.35–0.71, respectively. This complementary analysis to the clinical PK‐DDI studies confirmed the relevant influence of CYP2C9 polymorphism on the DDI behavior of siponimod and represented the basis for the DDI labeling recommendations.
Effect of face mask therapy on mandibular rotation considering initial and final vertical growth pattern: A longitudinal study
Authors: Salazar Liseth , Piedrahita Melissa , Álvarez Emery , Santamaría Adriana , Manrique Ruben , Oliveira Junior Osmir Batista
Published: June 2019

Objectives

To evaluate the effect of maxillary protraction with facemask therapy on mandibular rotation taking into account the initial and final vertical growth pattern of each participant in order to evaluate our null hypothesis: The use of facemask in these patients does not modify their initial vertical growth pattern.

Material and Methods

A prospective single cohort study included children with Class III malocclusion treated with rapid palatal expansion and maxillary protraction with facemask. Cephalograms were taken before commencement and after completion of the facemask therapy with standardized equipment and magnification. Intraindividual cephalometric measurements were compared, and the vertical growth patterns were classified according to cephalometric standards. Potential changes in vertical growth pattern before and after completion of the facemask therapy was assessed by measuring Pearson's chi‐square and by multiple correspondence analysis.

Results

Thirty‐eight study participants were recruited, aged between 5.2 to 9.5 years (mean 7.5) at the commencement of facemask therapy, which lasted on average 1.6 years. Differences on pretherapy and posttherapy cephalograms were seen for linear rotational and sagittal measurements (p < .01) as well as angular measurements of the cranial base, including an average palatal plane rotation of 0.45° (standard deviation: 1.78) and an average mandibular rotation of 0.39° (standard deviation: 2.19). The majority of participants maintained their initial vertical growth pattern after facemask therapy according to the multiple correspondence analysis (p < .001).

Conclusion

Facemask therapy does not modify vertical growth pattern. The observed changes suggest a trend of maintaining each patient's initial growth direction after therapy.
Do board characteristics affect environmental performance? A study of EU firms
Authors: García Martín C. José , Herrero Begoña
Published: June 2019

This paper explores the relationship between board characteristics and environmental performance. We adopt a triple perspective of environmental performance, focussing on emissions (waste and CO2), resource consumption (water and energy), and the implementation of environmental initiatives. The sample comprises 644 nonfinancial European Union–based companies. The data cover the period 2002 to 2017. The results confirm that gender diversity and the existence of a corporate social responsibility committee are positively associated with the firms' environmental performance. This finding is consistent with the view that the educational background, talent, and experience of women help promote sustainable environmental initiatives. The existence of a corporate social responsibility committee reflects a company's commitment to sustainable development.
Performance analysis of secure communications over correlated slow‐fading additive white Gaussian noise channels
Authors: Khodadoust Ali Mohammad , Khodadoust Javad , Irshad Azeem , Chaudhry Shehzad Ashraf
Published: June 2019

The broadcast nature of communications in wireless communication networks makes it vulnerable to some attacks, particularly eavesdrop attack. Hence, information security can have a key role to protect privacy and avoid identity theft in these networks, especially in distributed networks. In the wireless systems, the signal propagation is affected by path loss, slow fading (shadowing), and fast fading (multi‐path fading). As we know, there is a correlation between communication channels in the real radio environments. This correlation is defined by the correlation between their shadowing and/or multipath fading factors. So when there are several channels in the wireless systems, there is certainly a correlation between the channels. In this paper, we assume that the transmitter knows the full channel state information (CSI), it means the transmitter knows both the channel gains of the illegitimate (ie, eavesdropper) and the legitimate receivers and study the performance of secure communications of single‐input single‐output (SISO) systems consisting of single antenna devices, in the presence of a single antenna passive eavesdropper over correlated slow fading channels, where the main (transmitter to legitimate receiver) and eavesdropper (transmitter to illegitimate receiver) channels are correlated. Finally, we present numerical results and verify the accuracy of our analysis by Monte‐Carlo simulations.
Land‐use and climatic causes of environmental novelty in Wisconsin since 1890
Authors: Williams John W. , Burke Kevin D. , Crossley Michael S. , Grant Daniel A. , Radeloff Volker C.
Published: June 2019

Multiple global change drivers are increasing the present and future novelty of environments and ecological communities. However, most assessments of environmental novelty have focused only on future climate and were conducted at scales too broad to be useful for land management or conservation. Here, using historical county‐level data sets of agricultural land use, forest composition, and climate, we conduct a regional‐scale assessment of environmental novelty for Wisconsin landscapes from ca. 1890 to 2012. Agricultural land‐use data include six cropland types, livestock densities for four livestock species, and human populations. Forestry data comprise biomass‐weighted relative abundances for 15 tree genera. Climate data comprise seasonal means for temperature and precipitation. We found that forestry and land use are the strongest cause of environmental novelty (NoveltyForest = 3.66, NoveltyAg = 2.83, NoveltyClimate = 1.60, with Wisconsin's forests transformed by early 20th‐century logging and its legacies and multiple waves of agricultural innovation and obsolescence. Climate change is the smallest contributor to contemporary novelty, with precipitation signals stronger than temperature. Magnitudes and causes of environmental novelty are strongly spatially patterned, with novelty in southern Wisconsin roughly twice that in northern Wisconsin. Forestry is the most important cause of novelty in the north, land use and climate change are jointly important in the southwestern Wisconsin, and land use and forest composition are most important in central and eastern Wisconsin. Areas of high regional novelty tend also to be areas of high local change, but local change has not pushed all counties beyond regional baselines. Seven counties serve as the best historical analogues for over one‐half of contemporary Wisconsin counties (40/72), and so can offer useful historical counterparts for contemporary systems and help managers coordinate to tackle similar environmental challenges. Multi‐dimensional environmental novelty analyses, like those presented here, can help identify the best historical analogues for contemporary ecosystems, places where new management rules and practices may be needed because novelty is already high, and the main causes of novelty. Separating regional novelty clearly from local change and measuring both across many dimensions and at multiple scales thus helps advance ecology and sustainability science alike.
Influence of an abscisic acid (ABA) seed coating on seed germination rate and timing of Bluebunch Wheatgrass
Authors: Richardson William C. , Badrakh Turmandakh , Roundy Bruce A. , Aanderud Zackary T. , Petersen Steven L. , Allen Phil S. , Whitaker Dallin R. , Madsen Matthew D.
Published: June 2019

Semi‐arid rangeland degradation is a reoccurring issue throughout the world. In the Great Basin of North America, seeds sown in the fall to restore degraded sagebrush (Artemisia spp.) steppe plant communities may experience high mortality in winter due to exposure of seedlings to freezing temperatures and other stressors. Delaying germination until early spring when conditions are more suitable for growth may increase survival. We evaluated the use of BioNik™ (Valent BioSciences LLC) abscisic acid (ABA) to delay germination of bluebunch wheatgrass (Pseudoroegneria spicata). Seed was either left untreated or coated at five separate rates of ABA ranging from 0.25 to 6.0 g 100 g−1 of seed. Seeds were incubated at five separate constant temperatures from 5 to 25°C. From the resultant germination data, we developed quadratic thermal accumulation models for each treatment and applied them to 4 years of historic soil moisture and temperature data across six sagebrush steppe sites to predict germination timing. Total germination percentage remained similar across all temperatures except at 25°C, where high ABA rates had slightly lower values. All ABA doses delayed germination, with the greatest delays at 5–10°C. For example, the time required for 50% of the seeds to germinate at 5°C was increased by 16–46 d, depending on the amount of ABA applied. Seed germination models predicted that the majority of untreated seed would germinate 5–11 weeks after a 15 October simulated planting date. In contrast, seeds treated with ABA were predicted to delay germination to late winter or early spring. These results indicate that ABA coatings may delay germination of fall planted seed until conditions are more suitable for plant survival and growth.
Genetic diversity, admixture, and hatchery influence in Brook Trout (Salvelinus fontinalis) throughout western New York State
Authors: Beer Stephanie Dowell , Cornett Scott , Austerman Peter , Trometer Betsy , Hoffman Thomas , Bartron Meredith L.
Published: June 2019

Although Brook Trout are distributed across most of eastern North America, population numbers have declined in many regions due to habitat loss, climate change, and competition with non‐native species. In New York State, Brook Trout habitat has been substantially reduced, with many areas showing complete extirpation of Brook Trout populations, predominantly in the western portion of the state. Small, fragmented populations are at risk of genetic diversity loss, inbreeding depression, and reduced fitness, leading to a greater potential for local extirpation. Genetic monitoring is a practical tool that can facilitate further conservation‐decision making regarding small populations. In this study, we used 12 microsatellite loci to examine 3,436 sampled Brook Trout, representing 75 sites from the Allegheny, Erie/Niagara, Genesee, Oswego, Lake Ontario, and Susquehanna drainage basins throughout western New York State. Three Brook Trout hatchery strains were also genetically characterized to evaluate the degree of hatchery introgression between wild populations and hatchery strains stocked in the region. Overall, estimates of genetic diversity varied widely: Allelic richness ranged from 2.23 to 7.485, and expected heterozygosity ranged from 0.402 to 0.766. As observed for Brook Trout in other regions, we found a high degree of genetic differentiation among populations, with all comparisons except one showing significant FST values. Hatchery introgression was found to be minimal, with estimates ranging from 1.96% to 3.10% of wild individuals exhibiting membership proportions to a hatchery strain cluster exceeding 10% (q ≥ 0.10). Results from this investigation can be used to prioritize management efforts for Brook Trout in western New York State and act as a baseline to monitor future population trends.
Layer‐by‐Layer Coating of Cobalt‐Based Ink for Large‐Scale Fabrication of OER Electrocatalyst
Authors: Urgunde Ajay B. , Kamboj Vipin , Kannattil Hamid P. , Gupta Ritu
Published: June 2019

The scalability and stability of electrocatalysts is one of the biggest challenges for their practical applicability. In this context, Co3O4 nanoparticles conformally coated on a light weight, 3D and highly conducting carbon cloth are fabricated using an easily synthesized cobalt hexadecylthiolate complex as ink. This method is especially useful for large‐scale production as the complex is synthesized in large quantities and coated on 3D substrates by a simple dip‐coating method. The optimum loading of the catalyst is achieved through a layer‐by‐layer (LbL) assembly of a cobalt hexadecylthiolate complex via repeated dip coating of the carbon cloth electrode in the solution. The Co3O4/CC undergoes electrochemical oxidation and converts to CoOOH as an active species and acts as a highly efficient electrocatalyst with optimized loading. The Co3O4‐16/CC with 16 times dip coating exhibits remarkable stability over 24 h with an overpotential of 300 mV at 10 mA cm−2 and a Tafel slope of 77.06 mV dec−1. The electrocatalytic activity of Co3O4‐16/CC prepared by LbL coating is better than conventional Co3O4 and comparable to IrO2 and RuO2 electrocatalysts with the future possibility of commercial‐scale production at lower cost.
The effect of neutral electrolyzed water as a disinfectant of eggshells artificially contaminated with Listeria monocytogenes
Authors: Rivera‐Garcia Andres , Santos‐Ferro Liliana , Ramirez‐Orejel Juan C. , Agredano‐Moreno Lourdes T. , Jimenez‐Garcia Luis F. , Paez‐Esquiliano David , Andrade‐Esquivel Eduardo , Cano‐Buendia Jose A.
Published: June 2019

Neutral electrolyzed water (NEW) was tested as a disinfectant against Listeria monocytogenes on the surface of table eggs. Eggs were collected from a single Bovans White flock and were exposed to L. monocytogenes. Artificially contaminated eggs were divided into three different treatment groups: NEW, 2% citric acid solution (CAS), and saline solution (SS). To evaluate the bactericidal effect, the Mexican norm for antimicrobial activity determination protocol was performed. The observed bactericidal effect was compared against those obtained from CAS and SS. Bacterial cells present on the eggshells were quantified. NEW exhibited a significantly higher bactericidal effect than CAS when evaluated on the surfaces of chicken eggshells (6.11 log10CFU/ml reduction in vitro and a 2.18 log10 CFU/egg reduction on eggs vs. 1.06 log10CFU/ml in vitro reduction and 1.74 log10CFU/egg). Additionally, CAS was found to react with the carbonate egg shield, resulting in a loss of cuticle integrity. Mineral content of NEW‐treated eggshells was similar to SS‐treated eggshells; however, CAS‐treated eggshells showed a significant decrease in phosphorous concentration compared to NEW treatment. In this study, we demonstrated the effect of NEW and CAS on the integrity of the L. monocytogenes wall using transmission electron microscopy. To the best of our knowledge, this is the first report of the effect of NEW against L. monocytogenes on eggshells. Our results show that NEW is a viable alternative solution for the disinfection of table eggs that does not affect the cuticle or shell.
Effects of distribution of sugars and organic acids on the taste of strawberries
Authors: Ikegaya Atsushi , Toyoizumi Tomoyasu , Ohba Seiji , Nakajima Teruko , Kawata Tomoaki , Ito Seiko , Arai Eiko
Published: June 2019

The concentrations of sugars and organic acids as well as the total soluble solid (TSS) in different parts of the strawberry fruit were characterized. The data were used to create simulated fruit juice jellies, in order to clarify how the sugar and organic acid levels affect the taste. Such an approach eliminates the influence of external factors such as size, color, and texture when using real fruits in sensory evaluations. Further, the use of a jelly allowed us to simulate the concentration differences between various parts of the fruit. In the strawberry fruit, the sugar content is higher in the apex than in the peduncle; however, the level of organic acids is the same throughout. It was revealed that the sweetness and sourness in the apex and peduncle could be sufficiently recognized by humans as tastes. Also, a layered jelly sample replicating the sugar and acid distribution in real strawberry was perceived as less sweet and more sour, compared to a homogeneous one with the same overall composition. The likely reason is that the sourness in the peduncle is accentuated by the low TSS level, which decreases the TSS/total organic acid ratio that affects the sweetness/sour perceptions. Based on these results, factors for the appropriate sensory evaluation of fresh fruits in general were considered. Specifically, the distribution of sugars and organic acids in the fruit should be analyzed first, and bite‐sized parts with concentrations close to the average provide the most accurate evaluation results.
The effects of dietary cottonseed meal and oil supplementation on laying performance and egg quality of laying hens
Authors: Mu Yang , Zhu Luo‐Yi , Yang Ao , Gao Xin , Zhang Niya , Sun Lvhui , Qi Desheng
Published: June 2019

Cottonseed meal (CSM) and cottonseed oil (CSO), two cottonseed products, are rich in protein and lipids, respectively, but their use is limited by antinutritional factors in the products. This study investigated the effect of different dietary levels of CSM and CSO supplementation on the laying performance and egg quality of laying hens. A total of 162 24‐week‐old Hy‐Line brown laying hens were randomly assigned to diets supplemented with 0, 6%, or 12% CSM and 0, 2%, or 4% CSO in a 3 × 3 factorial design. During the 8‐week feeding trial, laying performance and egg quality parameters were measured weekly. Furthermore, a texture profile analysis (TPA) of the egg yolks was conducted, and the fatty acid profiles and protein composition of the yolks were measured to further determine egg quality. CSM supplementation decreased (p < 0.01) egg production and feed efficiency and increased (p < 0.01) yolk color, eggshell rate, and shell thickness, but had no significant effects on the TPA parameters, fatty acid profiles, and protein components of egg yolks. CSO supplementation resulted in decreases (p < 0.01) in egg production, egg weight, and feed efficiency and an increase (p < 0.01) in yolk color. In addition, CSO supplementation with two weeks of cold storage changed the physical properties of boiled egg yolks, as indicated by increased (p < 0.01) hardness, springiness, cohesiveness, and chewiness. Furthermore, 4% CSO supplementation increased the ratio of saturated/monounsaturated fatty acids (SAFA/MUFA) and the protein content of egg yolks, which was accompanied by a modified protein composition. These results indicate that CSM supplementation reduces laying performance and egg quality, and CSO supplementation decreases laying performance and results in egg yolk hardening by modifying its components.
Reaction Mechanism and Impact of Microstructure on Performances for the LSCF‐CGO Composite Electrode in Solid Oxide Cells
Authors: Effori E. , Moussaoui H. , Monaco F. , Sharma R. K. , Debayle J. , Gavet Y. , Delette G. , Si Larbi G. , Siebert E. , Vulliet J. , Dessemond L. , Laurencin J.
Published: June 2019

The reaction mechanism and the impact of microstructure on performances for a porous LSCF‐CGO composite used as O2 electrode in SOCs have been investigated. For this purpose, an integrated approach coupling (i) electrochemical testing, (ii) advanced 3D characterizations, and (iii) modeling was proposed. In this frame, a symmetrical cell was tested in a three‐electrode setup and the microstructure of the LSCF‐CGO working electrode was reconstructed by FIB‐SEM tomography. The experimental polarization curves and the impedance diagrams along with the extracted microstructural parameters were used to validate an in‐house microscale electrochemical model. This model considers two parallel reaction pathways with (i) an oxidation/reduction at TPBls (surface path) and (ii) an oxygen transfer at the gas/LSCF interface (bulk path). It was shown that the LSCF‐CGO electrode reaction mechanism is mostly controlled by the charge transfer at TPBls whatever the polarization. Finally, the impact of electrode composition, porosity and particles size on the cell polarization resistance was investigated by using the electrochemical model in combination with a large dataset of synthetic microstructures generated by a geometrical stochastic model. The effect of each microstructural parameter on the electrode performance was analyzed in order to provide useful guidelines for the cell manufacturing.
A systematic review and meta‐analysis of prognostic factors for remission in fertility‐sparing management of endometrial atypical hyperplasia and adenocarcinoma
Authors: Guillon Sarah , Popescu Nathalie , Phelippeau Juliette , Koskas Martin
Published: June 2019

Background

Endometrial cancer and atypical hyperplasia are rare in young women but create a dilemma between desire for pregnancy and oncologic outcomes.

Objective

To identify remission rates and associated prognostic factors in patients undergoing fertility‐sparing management for endometrial cancer and atypical hyperplasia.

Search strategy

MEDLINE was searched for studies published between January 1, 1950 and July 31, 2017 using various search terms.

Selection criteria

Studies evaluating fertility‐sparing management in patients aged between 19 and 44 years with atypical hyperplasia or stage I endometrial cancer.

Data collection and analysis

Use of PRISMA guidelines to conduct a meta‐analysis of the proportion of patients in remission and meta‐regression analysis to test the effect of possible prognostic factors for remission.

Main results

A total of 3673 studies were screened; 65 studies including 1604 patients met the inclusion criteria. The remission rate was 0.75 (95% CI, 0.73–0.77). Operative hysteroscopy for endometrial sampling was associated with higher remission rates (OR 2.31; 95% CI, 1.10–4.84; P=0.03). Studies with higher ratios of infertile women were associated with higher remission rates (OR 4.21; 95% CI, 1.44–12.33; P<0.01).

Conclusion

Operative hysteroscopy is the preferred endometrial sampling method for patients with atypical hyperplasia or endometrial cancer undergoing fertility‐sparing management.
Quantitative evaluation on 3D fetus morphology via X‐ray grating based imaging technique
Authors: Ji Xuewen , Liu Huiqiang , Xing Yan , Xue Yanling
Published: June 2019

Synchrotron‐based X‐ray phase sensitive micro‐tomography techniques enable to visualize detailed three‐dimensional (3D) insight into nondestructive inner‐structure of biomedical samples. Different phase sensitive mechanisms have been employed for discrimination of tissue's tiny density variations in biomedical research. We effectively visualized and analyzed the phase‐contrast experimental results of X‐ray grating‐based imaging, based on grating interferometry with phase stepping, by using transgenic mouse fetus. We quantitatively measured and evaluated the contrast‐to‐noise ratio or the mass density resolution, spatial resolution, radiation dose, and figure of merit of X‐ray grating‐based imaging technique in biomedical research respectively. Moreover, the complex coherent degrees of light source were duly taken into account in the analysis of spatial resolution. In addition, the mass density distribution of soft biomedical specimens can be estimated using our presented method preliminarily. For most soft tissue and organ observation, this work provides explicit guidelines to help future synchrotron users obtain the quantitative image information, suitable for their specific biomedical research.
Systematic studies on mechanochemical synthesis: Schiff bases from solid aromatic primary amines and aldehydes
Authors: Tigineh Getinet Tamiru , Liu Ling‐Kang
Published: June 2019

A versatile and robust mechanochemical route to Aldehyde–Schiff base conversions has been established for a broad range of aldehydes via a simple cogrinding in mortar with a pestle under a solvent‐free, as well as solvent‐assisted, environment. The extent of amines reactivity under these conditions has also been explored, along with an examination of the possible connection between reactivity and electronic substituent effects. Results obtained demonstrated that the solvent‐free mechanochemical conversion of p‐toluidine and aromatic aldehydes to the corresponding Schiff bases proceeded more smoothly than the corresponding synthesis with 4‐aminobenzonitrile. The present approach not only provides good to excellent yields but also eliminates the disadvantages of the traditional synthesis of Schiff bases, such as the use of hazardous solvents, more or less demand of expensive catalysts, and looking for optimization on reaction conditions.
Design, synthesis, and antilung adenocarcinoma activity research of novel paeonol Schiff base derivatives containing a 1,2,3‐triazole moiety
Authors: Jiang Yuqin , Li Yanyan , Yang Tingting , Shi Xin , Suo Huajun , Zhang Weiwei , Xu Guiqing , Li Wei
Published: June 2019

A new series of paeonol Schiff base derivatives containing a 1,2,3‐triazole moiety were synthesized using the copper(I) catalyzed azide‐alkynecycloaddition (CuAAC) reaction and evaluated for their cytotoxicity in vitro against human cervical carcinoma HeLa cells, human lung cancer A549 cells, and human liver cancer HepG2 cells. Unfortunately, all the tested compounds showed poor activities toward the human cervical carcinoma HeLa cells and human liver cancer HepG2 cells. However, compounds (E)‐2‐(1‐(((1‐[2‐fluorophenyl]‐1H‐1,2,3‐triazol‐4‐yl)methyl)imino)ethyl)‐5‐methoxyphenol (4c) and (E)‐2‐(1‐(((1‐[3‐ chlorophenyl]‐1H‐1,2,3‐triazol‐4‐yl)methyl)imino)ethyl)‐5‐methoxyphenol (4i) exhibited inhibitory activities toward human lung cancer A549 cells (IC50 = 45.1 μM for 4c and 78.9 μM for 4i) compared with that of paeonol, which indicated that such paeonol Schiff base derivatives containing a 1,2,3‐triazole moiety could be further modified to obtain good cytotoxicity in vitro against human lung cancer A549 cells.
Detection of Hb H disease caused by a novel mutation and ‐‐SEA deletion using capillary electrophoresis
Authors: Li Youqiong , Liang Liang , Tian Mao , Qin Ting , Wu Xin
Published: June 2019

Background

Hb H disease is a serious type of α‐thalassemia which cause moderate anemia while misdiagnosis by routine genetic analysis in a rare or novel Hb H disease.

Methods

The study was done on three patients and one fetus in a suspected Hb H disease family. Hb analysis was carried out using capillary electrophoresis (CE), and hematological analysis was conducted with an automated cell counter. Common α‐ and β‐thalassemia mutations were detected by routine genetic analysis (gap‐PCR and RDB‐PCR). Novel mutation diagnostic methods were based on DNA sequencing.

Results

Capillary electrophoresis revealed clinical feature of classic Hb H disease in the proband, and hematology analysis showed moderate anemia (Hb 87 g/L). But routine genetic analysis was found that it was only a heterozygote for the ‐‐SEA deletion. DNA sequencing of α‐globin genes (α1 and α2) identified the breakpoints between nts 34162 and 34171 at α2 gene, named CD 90‐93 (‐AGCTTCGG) mutation. The genotype of proband and fetus was the same ‐‐SEA/‐αCD90‐93. His father was homozygous for the novel mutation (‐αCD90‐93/‐αCD90‐93), and his mother was heterozygote for the ‐‐SEA deletion.

Conclusions

Our study for the first time described the novel mutation CD 90‐93 (‐AGCTTCGG). CE is a way to avoid misdiagnosis of rare or novel Hb H disease.
Photoautotrophic cultivation of Chlorococcum humicola in stirred tank and airlift photobioreactors under different light settings and light supplying strategies for biomass and carotenoid production
Authors: Powtongsook Sorawit , Nootong Kasidit
Published: June 2019

BACKGROUND

Light quality influences biomass and carotenoid production in microalgae, yet no information is available for Chlorococcum humicola. This work performed a series of batch cultivations of Chlorococcum humicola to assess biomass and carotenoid production in stirred tank and airlift photobioreactors under different light qualities and supplying strategies.

RESULTS

White light was preferred for growth while blue light was suitable for carotenoid production during stationary phase. Batch cultivation in stirred tank photobioreactors subjected to two‐staged lighting yielded higher carotenoid productivity than single‐staged lighting, with the highest productivity obtained when providing white light at 5000 lx during growth phase and combination of white (100 000 lx) and blue (5000 lx) lights during stationary phase. Subsequent cultivation in internal‐loop airlift photobioreactors under optimal light setting based on two‐staged study produced higher biomass (855 ± 26 mg L−1) and carotenoid (8.11 ± 0.20 mg L−1 or 9.23 ± 0.23 mg g−1) than the cultivation in stirred tank systems with the same volume and operating condition. High‐performance liquid chromatography (HPLC) analysis of carotenoid from airlift photobioreactors revealed that lutein, violaxanthin and neoxanthin were major carotenoids.

CONCLUSIONS

This work reported for the first time the effect of light quality and supplying strategy on growth and carotenoid production in Chlorococcum humicola. Two‐staged lighting with white light following by combination of white light at high intensity and blue light offered new strategy to improve carotenoid productivity. Cultivation in airlift photobioreactor yielded higher biomass than the cultivation in stirred tank photobioreactors and offered an alternative for future photobioreactor selection. © 2019 Society of Chemical Industry
Female family members lack understanding of indeterminate negative BRCA1/2 test results shared by probands
Authors: Himes Deborah O. , Gibbons Deborah K. , Birmingham Wendy C. , Beckstrand Renea L. , Gammon Amanda , Kinney Anita Y. , Clayton Margaret F.
Published: June 2019

Genetic test results have important implications for close family members. Indeterminate negative results are the most common outcome of BRCA1/2 mutation testing. Little is known about family members' understanding of indeterminate negative BRCA1/2 test results. The purpose of this mixed‐methods study was to investigate how daughters and sisters received and understood genetic test results as shared by their mothers or sisters. Participants included 81 women aged 40–74 with mothers or sisters previously diagnosed with breast cancer and who received indeterminate negative BRCA1/2 test results. Participants had never been diagnosed with breast cancer nor received their own genetic testing or counseling. This Institutional Review Board‐approved study utilized semi‐structured interviews and surveys. Descriptive coding with theme development was used during qualitative analysis. Participants reported low amounts of information shared with them. Most women described test results as negative and incorrectly interpreted the test to mean there was no genetic component to the pattern of cancer in their families. Only seven of 81 women accurately described test results consistent with the meaning of an indeterminate negative. Our findings demonstrate that indeterminate negative genetic test results are not well understood by family members. Lack of understanding may lead to an inability to effectively communicate results to primary care providers and missed opportunities for prevention, screening, and further genetic testing. Future research should evaluate acceptability and feasibility of providing family members letters they can share with their own primary care providers.
Impact of genotypic susceptibility score on cART outcomes during primary HIV infection
Authors: Giacomelli Andrea , Fabbiani Massimiliano , De Benedetto Ilaria , Nozza Silvia , Focà Emanuele , Celesia Benedetto M. , Marchetti Giulia , Mussini Cristina , Antinori Andrea , d’Ettorre Gabriella , Madeddu Giordano , Bandera Alessandra , Muscatello Antonio , Rusconi Stefano
Published: June 2019

To assess the impact of genotypic susceptibility score (GSS) on combined antiretroviral therapy (cART) outcomes during primary HIV infection (PHI) we retrospectively enrolled patients with PHI diagnosed between 2008 and 2015 at 9/24 Italian Network ACuTe HIV InfectiON centers. One hundred‐seventy‐six patients were enrolled. Of these, 55 (32.9%) patients started with more than three drugs and 11 (7.2%) started with a GSS < 3. Regimen's GSS (per 1 point increase) (adjusted odds ratio [aOR], 4.82; 95% confidence interval [CI], 1.62‐14.28; P = .005) and baseline HIV‐RNA (per 1 log10 increase) (aOR, 2.02; 95% CI, 1.09‐3.73; P = .025) resulted associated with early cART initiation. In conclusion, regimen's GSS resulted to be associated to the time to cART initiation during PHI.
Characteristics of thermal and momentum transport during the lifetime of Ural blocking highs
Authors: Li Yan , Lu Yao , Wang Chenghai
Published: June 2019

Ural blocking (UB) event is an important large‐scale weather system dominating cold waves in East Asia. This paper investigates the thermal‐dynamical variation characteristics associated with UB evolution via 32 UB events in winter during 1979–2016. The results show that transport of stationary heat and momentum changes prominently from 3 and 6 days before and after UB establishment. Specifically, on 3 days prior to the UB event establishment, an apparent convergence of stationary heat flux ({v*T*}), which can extend from lower‐middle troposphere to the tropopause, is observed at around 60°N in the Urals region. The diagnosis shows that the convergence of stationary heat flux weakens the meridional temperature gradient () and thermal wind, and thus the zonal westerly weakens. The convergence of ({v*T*}) also support formation of the warm centre structure of UB event. Meanwhile, convergence of momentum flux reverses to be a divergence in the Urals region (60°N), which contributes to decrease of the zonal wind. The heat and momentum flux reduce the intensity of the westerly and are beneficial for the establishment of UB event. Along with UB event establishment, the convergence of stationary heat flux weakens, and the divergence of momentum flux strengthens, accompanying with decrease of wind speed at middle latitudes and maintaining of the UB event. Six days later, the convergence of stationary heat flux disappears and divergence of momentum flux changes to be convergence and then the UB event collapses. Further analyses also suggest that the polar front jet (PFJ) enhances (weakens) coincidently before (after) the establishment of UB, which is attributed to the strengthening (weakening) of the convergence of ({u*v*}) around 70°N.
Succession management success at PT Bakrie Brothers Tbk
Authors: Rosen Vidi , Luddin Muchlis R. , Supriyati Yetti
Published: June 2019

The succession process is critical to the success of any business, but presents particular challenges in family firms. In its 77 years of operation, PT Bakrie Brothers Tbk has grown to become one of the largest family businesses in Indonesia and is now looking forward to the fourth generation of family leadership, thanks to a precisely articulated succession management framework that also develops leaders from outside the family. An analysis of the company's experiences shows that four factors underlie its management succession program: a stated desire to be sustainable; an emphasis on entrepreneurship; adherence to corporate cultural values; and a well‐structured leadership development process that focuses on team dynamics, corporate vision and values, ethics and sustainability, communication, business execution and operational excelllence, and intrapreneurship, innovation, and creativity.
Combining career and care‐giving: The impact of family‐friendly policies on the well‐being of working mothers in the United Kingdom
Authors: Javed Uzma
Published: June 2019

Taking into account variations in family structure among working mothers, this study examines the effect of family‐support policies on the well‐being of 4,247 female employees in Britain who have never married, are married, or are divorced, separated, or widowed. Based on data from the British Workplace Employment Relations Survey of 2011, the study found that not all family‐friendly policies were equally effective in alleviating anxiety and depression or in fostering job satisfaction among working mothers. Although having the option to work the same number of hours across fewer days per week was shown to be beneficial to the well‐being of never‐married mothers, flextime was beneficial to divorced, separated, or widowed mothers. Having the chance to reduce work hours, work from home, or work only during the school term was most beneficial to the well‐being of married mothers. These findings bolster arguments that the availability of family‐support policies in the workplace enhances the effectiveness of working mothers in both their work and family roles, thereby positively affecting their overall well‐being. They also highlight the role that individuals' family structures may play in the use of those initiatives.
Microfluidic time‐lapse analysis and reevaluation of the Bacillus subtilis cell cycle
Authors: Lee Seoungjun , Wu Ling Juan , Errington Jeff
Published: June 2019

Recent studies taking advantage of automated single‐cell time‐lapse analysis have reignited interest in the bacterial cell cycle. Several studies have highlighted alternative models, such as Sizer and Adder, which differ essentially in relation to whether cells can measure their present size or their amount of growth since birth. Most of the recent work has been done with Escherichia coli. We set out to study the well‐characterized Gram‐positive bacterium, Bacillus subtilis, at the single‐cell level, using an accurate fluorescent marker for division as well as a marker for completion of chromosome replication. Our results are consistent with the Adder model in both fast and slow growth conditions tested, and with Sizer but only at the slower growth rate. We also find that cell size variation arises not only from the expected variation in size at division but also that division site offset from mid‐cell contributes to a significant degree. Finally, although traditional cell cycle models imply a strong connection between the termination of a round of replication and subsequent division, we find that at the single‐cell level these events are largely disconnected.
Identification of a novel large deletion and other copy number variations in theCFTRgene in patients with Cystic Fibrosis from a multiethnic population
Authors: Martins Raisa da Silva , Campos Junior Mario , dos Santos Moreira Aline , Marques Zembrzuski Verônica , da Fonseca Ana Carolina Proença , Abreu Gabriella de Medeiros , Cabello Pedro Hernan , de Cabello Giselda Maria Kalil
Published: June 2019

Background

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). There are over 2000 different pathogenic and non‐pathogenic variants described in association with a broad clinical heterogeneity. The most common types of mutations in this gene are single nucleotide substitutions or small deletions and insertions. However, large rearrangements, such as large duplications or deletions, are also a possible cause of CF; these variations are rarely tested in routine screenings, and much of them remain unidentified in some populations, especially those with high ethnic heterogeneity.

Methods

The present study utilized the Multiplex Ligation‐dependent Probe Amplification (MLPA) technique for the detection of duplications and deletions in 165 CF patients from the Rio de Janeiro State (Brazil), which after extensive mutational screening, still exhibited one or two unidentified CF alleles.

Results

Five patients with alterations in MLPA signals were detected. After validation, we identified three copy number variations, one large duplication (CFTRdup2‐3) and two large deletions (CFTRdel25‐26 and CFTRdel25‐27‐CTTNBP2). Two detected deletions were not validated. They were false positives caused by a small deletion of 18 base pairs (232del18) and a point mutation (S168L) in the probe binding site.

Conclusion

Our results highlight the importance of screening for large rearrangements in CF cases with no or only oneCFTRmutation defined.
Neonatal Adipocytokines and Longitudinal Patterns of Childhood Growth
Authors: Buck Catherine O. , Eliot Melissa N , Kelsey Karl T. , Chen Aimin , Kalkwarf Heidi , Lanphear Bruce P. , Braun Joseph M.
Published: June 2019

Objective

Adipocytokines are markers of fetal metabolism, but their association with childhood growth is unclear. This study examined associations of neonatal adipocytokines with longitudinal childhood adiposity measures in a prospective cohort of pregnant women and their children.

Methods

Leptin and adiponectin concentrations at delivery and children’s BMI z scores between age 4 weeks and 8 years were measured. Differences in BMI z scores and rates of BMI z score change by leptin (n = 257) and adiponectin (n = 271) terciles were estimated.

Results

Children in the middle (mean difference: 0.2; 95% CI: −0.1 to 0.4) and highest (0.4; 95% CI: 0.1 to 0.6) leptin terciles had greater BMI z scores than children in the lowest tercile. Associations were null after adjustment for birth weight z score. Children in the lowest adiponectin tercile had greater gains in BMI z score (change per year: 0.10; 95% CI: 0.08 to 0.13) than children in the middle (0.07; 95% CI: 0.04 to 0.09) and highest terciles (0.04; 95% CI: −0.01 to 0.05) (adiponectin × age interaction P < 0.001).

Conclusions

Lower adiponectin levels were associated with increased rates of BMI gains in the first 8 years of life. Though leptin was positively associated with BMI, this association may be confounded by birth weight.
Effect of Genetic Propensity for Obesity on Income and Wealth Through Educational Attainment
Authors: Patel Pankaj C. , Rietveld Cornelius A.
Published: June 2019

Objective

This study contributes to the literature on the income and wealth consequences of obesity by exploiting recent discoveries about the genetic basis of BMI.

Methods

The relation between a genetic risk score (GRS) for BMI, which reflects the genetic predisposition to have a higher body weight, and income and wealth was analyzed in a longitudinal data set comprising 5,962 individuals (22,490 individual‐year observations) from the US Health and Retirement Study.

Results

Empirical analyses showed that the GRS for BMI lowers individual income and household wealth through the channel of lower educational attainment. Sex‐stratified analyses showed that this effect is particularly significant among females.

Conclusions

This study provides support for the negative effects of the GRS for BMI on individual income and household wealth through lower education for females. For males, the effects are estimated to be smaller and insignificant. The larger effects for females compared with males may be due to greater labor market taste‐based discrimination faced by females.
Identification of gastrointestinal perforation based on ICD‐10 code in a Japanese administrative medical information database and associated drug exposure risk factors
Authors: Tanigawa Masatoshi , Kataoka Yoko , Kishino Takayoshi , Kohama Mei , Uyama Yoshiaki , Suzuki Yasuyuki , Yokoi Hideto
Published: June 2019

Purpose

The purpose of this study is to evaluate the accuracy of gastrointestinal (GI) perforation ICD‐10 coding in the Diagnosis Procedure Combination (DPC) database and to examine drug exposure risk factors for GI perforation.

Methods

A total of 100 patients with GI perforation ICD‐10 codes were selected randomly from Kagawa University Hospital's DPC database between April 2011 and December 2016. Two experienced specialist physicians independently reviewed the medical records and classified cases as “definite A,” “definite B,” “probable,” or “no GI perforation.” The positive predictive values (PPVs) of “definite A/B” cases were calculated after stratification by sex, age, ICD‐10 code, and diagnostic information in the DPC data. The number of prescribed drugs with side effects of GI perforation according to historical data was compared between “definite A/B” and “no GI perforation” cases.

Results

The overall PPV was 47.0% (95% confidence interval [CI], 36.9‐57.2). However, the PPVs for the three categories of diagnostic information in the DPC data (“main diagnosis,” “diagnosis causing admission,” and “most resource‐intensive diagnosis”) were each more than 70% after excluding inappropriate patients. Additionally, the PPV focused on these three categories was 76.3% (95% CI, 59.8‐88.6). Prescribed drugs with side effects of GI perforation were more frequently detected in “definite A/B” cases (P = .028).

Conclusions

Although the overall PPV for GI perforation based on ICD‐10 code was low, our results suggest that the PPV could be improved by appropriate selection of DPC diagnosis category and that use of multiple medications enhances the risk of GI perforation.
A potent fluorescent calcitonin gene‐related peptide analogue enables visualization of receptor internalization
Authors: Yule Lauren R. , Garelja Michael L. , Hendrikse Erica R. , Gingell Joseph J. , Poyner David R. , Harris Paul W. H. , Brimble Margaret A. , Hay Debbie L.
Published: June 2019

The calcitonin gene‐related peptide (CGRP) system provides a significant opportunity for the treatment of migraine. However, further understanding of the function of CGRP receptors is required. Fluorescent ligands are valuable probes that enable deeper understanding of peptide‐receptor interactions and receptor function. We herein report the synthesis and biological activity of a potent fluorescent CGRP that allowed direct observation of CGRP receptor internalization in a transfected cell system. The potent activity of this fluorescent CGRP thus enables access to a valuable pharmacological tool for further understanding the CGRP system.